Fibroblast Growth Factor Receptors and Ligands in Context of Bevacizumab Response in Ovarian Carcinoma: An Exploratory Analysis of AGO-OVAR11/ICON-7.

With more novel drugs being approved for the treatment of ovarian carcinoma, the question remains to what extent patients benefit from antiangiogenic treatment with bevacizumab, either in combination with poly-(ADP-ribose) polymerase inhibitors or as single-agent maintenance. As fibroblast growth factor receptors and their ligands (FGFRs/FGFs) are key players in angiogenic signaling and have been linked to resistance to several drugs, we investigated the prognostic or predictive potential of FGFs/FGFRs signaling in the context of bevacizumab treatment within the prospective phase III AGO-OVAR11/ICON-7 study. FGFR1, FGFR2, FGFR3, FGFR4, FGF1, and FGF19 gene expressions were determined in 380 ovarian carcinoma tumor samples collected from German centers in the multicenter phase III AGO-OVAR11 trial/ICON-7 trial. All patients received carboplatin and paclitaxel, administered every 3 weeks for 6 cycles, and were randomized to bevacizumab. Expressions of FGFR1, FGFR2, FGF1, and FGF19 were associated with progression-free survival in both uni- and multivariate (FGFR1: HR, 1.6, P < .001; FGFR2: HR, 1.6, P = .002; FGF1: HR, 2.3, P < .001; and FGF19: HR, 0.7; P = .007) analysis. A signature built by FGFR1, FGFR4, and FGF19 defined a subgroup (n = 62) of patients that derived the greatest bevacizumab-associated improvement of progression-free survival (HR, 0.3; P = .004). In this exploratory analysis of a prospective randomized phase III trial, we provide evidence that the expression of FGFRs/FGFs might have independent prognostic values. An FGFR/FGF-based gene signature identified in our study appears to predict long-term benefit from bevacizumab. This observation is hypothesis-generating and requires validation on independent cohorts.

Is there an association between endometriosis and subsequent breast cancer? A retrospective cohort study from Germany.

PURPOSE: Given the relatively high incidence of both endometriosis and breast cancer, investigating the potential connection between these gynecological diseases is of substantial clinical significance. However, there is no clear consensus in the literature on the extent to which the risk of breast cancer is increased in patients with endometriosis. Therefore, we conducted a large-scale observational study investigating the association between endometriosis and breast cancer risk. METHODS: This study included women aged ≥ 18 years with an initial endometriosis diagnosis from one of 315 office-based gynecologists in Germany between January 2005 and December 2021. Non-endometriosis patients were matched 1:1 to patients with endometriosis based on age, index year, average yearly consultation frequency, and predefined co-diagnoses within 12 months before or on the index date, including obesity and benign breast disorders. The association between endometriosis and the 10-year incidence of breast cancer was studied using Kaplan-Meier curves and log-rank tests. Finally, a univariable Cox regression analysis was conducted to assess the association between endometriosis and breast cancer. RESULTS: Over a follow-up period of up to 10 years, no significant difference was observed between the endometriosis (2.4%) and the matched non-endometriosis group (2.5%) with regard to breast cancer diagnoses. Furthermore, the regression analysis revealed no significant association between endometriosis and subsequent breast cancer. CONCLUSION: In summary, our comprehensive 10-year study involving a substantial sample of women indicates that endometriosis is not significantly associated with an increased risk of subsequent breast cancer.

German longitudinal prescription database (LRx): Description of characteristics, use in pharmacoepidemiological research, and limitations
.

Large databases have played a critical role in pharmacoepidemiological research in the last decade, with this role likely to gain further importance in the future. The aim of the present paper is to describe the characteristics, the recent use, and the limitations of the German longitudinal prescription (LRx) database. The LRx database contains patient-level data on prescriptions collected in retail pharmacies, corresponding to ~ 80% of prescriptions reimbursed by statutory health insurance funds in Germany. The LRx database includes a higher proportion of older adults and women compared to the overall German population with statutory health insurance. Coverage per family of drugs ranges from 71.8% for antiepileptics to 94.7% for urological agents. Multiple pharmacoepidemiological studies based on the data from the German LRx database have been published in the last years on topics such as patterns of prescription and treatment adherence and persistence. A large number of disorders have been investigated in this research (e.g., type 2 diabetes, inflammatory diseases, and psychiatric conditions). The major limitations of the LRx database are the lack of formal diagnoses and the absence of hospital data. In conclusion, the German LRx database could be a key source of data for future pharmacoepidemiological studies.

Changes in the incidence of early-onset breast cancer in Germany between 2010 and 2022.

PURPOSE: The aim of this study was to identify the mean age at which breast cancer (BC) was first diagnosed in 2010 or 2022, and to evaluate whether there were any changes in age groups at first BC diagnosis. METHODS: This retrospective cross-sectional study included adult women (18 years or older) who were diagnosed with BC (ICD-10: C50) for the first time in 2010 or 2022 in office-based practices in Germany (in 300 general practices or 95 gynecological practices). We examined the mean age at diagnosis and the percentage of patients in three age groups (18-49, 50-65, and > 65) for both 2010 and 2022. The average age difference between 2010 and 2022 was analyzed using Wilcoxon rank tests, and the proportions of the three age groups were analyzed using chi-squared tests. These analyses were performed separately for patients in general and gynecological practices. RESULTS: The mean age at which BC was initially diagnosed in 2022 was found to be significantly greater than that in 2010 for both general practices (66.9 years vs. 64.0 years p < 0.001) and gynecological practices (62.2 years vs. 60.3 years, p < 0.001). Early-onset BC decreased from 15.6 to 12.0% in general practices and from 23.2 to 18.2% in gynecological practices between 2010 and 2022. The proportion of new BC diagnoses in the age group 50-65 increased from 36.6 to 40.9% in gynecological practices, but did not increase in general practices. CONCLUSION: The study found that BC was diagnosed at an older age in 2022 than in 2010. In addition, the proportion of early-onset BC cases decreased, while the proportion of cases in the age group 50-65 increased in gynecological practices in Germany.

Association between gout and subsequent breast cancer: a retrospective cohort study including 67,598 primary care patients in Germany.

PURPOSE: The aim of this retrospective cohort study was to analyze the cumulative incidence of breast cancer following gout and to investigate the association between gout and subsequent breast cancer in 67,598 primary care patients in Germany. METHODS: This study included adult female patients (≥ 18 years) with an initial diagnosis of gout in 1284 general practices in Germany between January 2005 and December 2020. Individuals without gout were matched to gout patients using propensity score matching based on average yearly consultation frequency during the follow-up period, diabetes, obesity, chronic bronchitis/COPD diagnoses, and diuretic therapy. The 10-year cumulative incidence of breast cancer in the cohorts with and without gout was also studied using Kaplan-Meier curves, which were then compared using the log-rank test. Finally, a univariable Cox regression analysis was conducted to assess the association between gout and breast cancer. RESULTS: After up to 10 years of follow-up, 4.5% of gout and 3.7% of non-gout patients were diagnosed with breast cancer. A Cox regression analysis revealed a significant association between gout and subsequent breast cancer in the total population (HR: 1.17; 95% CI: 1.05-1.31). In the age-stratified analyses, gout was only strongly associated with subsequent breast cancer in the age group ≤ 50 (HR: 1.58; 95% CI: 1.10-2.27), but the association was not significant in women over 50 years old. CONCLUSION: Taken together, the findings of our study provide evidence for the association between gout and subsequent breast cancer diagnosis, particularly in the youngest age group.

Association between antihypertensive medication and the risk of urinary tract infection (UTI) of outpatients: a retrospective cohort study.

PURPOSE: The aim of this retrospective study was to investigate the impact of a broad spectrum of antihypertensive (AH) medications on urinary tract infections (UTI) of outpatients diagnosed in general practices in Germany. METHODS: This study included a total of 367,960 patients aged ≥ 18 years newly a diagnosed with UTI in 1274 general practices in Germany between January 2010 and December 2019. The analysis was conducted for five groups representing five AH therapy classes (diuretics (DIU); beta blockers (BB); calcium channel blockers (CCB); ACE inhibitors (ACEi); angiotensin II receptor blockers (ARB)), each containing 73,592 patients. A Cox regression model was used to analyze the association between each antihypertensive drug class and UTI incidence as compared to all other antihypertensive drug classes (as a group). RESULTS: The incidence of UTI diagnosis was slightly higher in patients treated with DIU (8.6%), followed by ACEi (8.1%), ARB (7.9%), and CCB (6.5%). Antibiotic therapy for UTI was given in 5.6% of DIU and 4.3% of CCB patients. The incidence of UTI and antibiotic therapy was much higher in women than in men across all therapy classes. No significant increase or decrease in UTI incidence or antibiotic therapy was observed in any of the AH therapy classes investigated. CONCLUSION: The present study did not identify a significant increase or decrease of UTI incidence or antibiotic therapy in patients treated with ACEi, ACB, CCB, beta blockers or diuretics. Across all AH classes studied, the incidence of UTI and antibiotic therapy was higher in women than in men, although not significantly.

Is there an association between breast cancer and incident adhesive capsulitis of the shoulder? A retrospective cohort study from Germany.

PURPOSE: Preliminary data suggest that women with breast cancer are at particularly high risk of adhesive capsulitis of the shoulder. Therefore, this study aimed to investigate the potential association between breast cancer and adhesive capsulitis in adults from Germany. METHODS: This retrospective cohort study included all women aged ≥ 18 years who were diagnosed for the first time with breast cancer in one of 1,274 general practices in Germany between January 2000 and December 2018 (index date). Women without breast cancer were matched (1:1) to those with breast cancer using a propensity score based on age at the index date, index year, and the average number of medical consultations per year during the follow-up. In women without breast cancer, the index date was a randomly selected visit date between 2000 and 2018. The association between breast cancer and the 10-year incidence of adhesive capsulitis was studied using Kaplan-Meier curves and a Cox regression model adjusted for age and several comorbidities. RESULTS: There were 52,524 women included in this study (mean [SD] age 64.2 [12.9] years). The 10-year incidence of adhesive capsulitis was 3.6% in both the group with and the group without breast cancer (log-rank p-value = 0.317). The Cox regression analysis further showed no significant association between breast cancer and adhesive capsulitis (HR = 0.96, 95% CI = 0.86-1.08). CONCLUSION: In this sample of women from Germany, breast cancer was not significantly associated with adhesive capsulitis. Although the present preliminary findings are reassuring, general practitioners should regularly assess shoulder function in breast cancer survivors.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1).

OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.

Positive association between body height and breast cancer prevalence: a retrospective study with 135,741 women in Germany.

PURPOSE: The aim of this study was to analyze the prevalence of breast cancer in relation to body height and to investigate associations between body height and breast cancer in Germany. METHODS: This retrospective cohort study included 135,741 adult women followed in one of 161 gynecology practices in Germany between January 2019 and December 2021. The 3 year prevalence of breast cancer (ICD-10: C50) during the study period was shown in relation to body height, which was included in this study as a five-category variable for women: ≤ 160 cm, 161-165 cm, 166-170 cm, 171-175 cm, > 175 cm. The associations between height and breast cancer were analyzed using logistic regression models adjusted for age and BMI. RESULTS: The prevalence of breast cancer increased from 5.1% in women ≤ 160 cm to 6.8% in women > 175 cm in the age group 51-60, and from 9.2% in women ≤ 160 cm to 12.2% in women 171-175 cm in the age group > 60 years. The OR for breast cancer was 1.18 (95% CI 1.12-1.24) for every 10 cm increase in height. Compared to height ≤ 160 cm, the OR for height 166-170 cm was 1.26 (1.15-1.39), for 171-175 cm 1.43 (1.27-1.61), and for > 175 cm 1.49 (1.28-1.74). CONCLUSION: The results of this study suggest that greater body height in women is significantly related to an increased breast cancer risk.

Incidence of other cancer diagnoses in women with breast cancer: a retrospective cohort study with 42,248 women.

PURPOSE: The aim of the present study was to determine whether women diagnosed with breast cancer (BC) have an increased incidence of other cancers, e.g., gastric cancer, lung cancer, skin cancer, and so on, compared to healthy women without a breast cancer diagnosis. METHODS: This retrospective cohort study was based on data from the Disease Analyzer database (IQVIA) and included adult women with an initial diagnosis of BC documented in one of 1,274 general practices in Germany between January 2000 and December 2018. Women with BC were matched to women without cancer by age, index year, yearly consultation frequency, and co-diagnoses. Univariate Cox regression models were used to study the association between BC and the incidence of other cancer diagnoses. RESULTS: 21,124 women with BC and 21,124 women (mean age: 63 years) without cancer were included. Within 10 years of the index date, 14.3% of women with BC and 10.0% of women without cancer were diagnosed with cancer (p < 0.001). BC was significantly associated with the incidence of other cancer diagnoses (HR: 1.42, p < 0.001). The strongest association was observed for respiratory organ cancer (HR = 1.69, p < 0.001), followed by female genital organ cancer (HR = 1.61, p < 0.001) and cancer of lymphoid and hematopoietic tissue (HR: 1.59, p < 0.001). CONCLUSION: The results of this study show that women with BC have an increased incidence of another cancer compared to women without cancer. Therefore, it is important to pay particular attention to the development of other malignancies during follow-up in patients with BC. This should be considered especially in patients with a proven genetic mutation.

Association between anti-seizure medication and the risk of lower urinary tract infection in patients with epilepsy.

PURPOSE: The aim of this retrospective study was to analyze the incidence of lower urinary tract infections (LUTI) and antibiotic prescriptions within 12 months after initial prescription of anti-seizure medication (ASM) between January and December 2020 (index date) and to investigate the association between a broad spectrum of ASMs and the risk of LUTI in patients with epilepsy. METHODS: This retrospective cohort study included a total of 9186 adult patients (≥18 years) with an initial diagnosis of epilepsy and a prescription of an ASM treated in 1284 general practices in Germany between January 2010 and December 2020 (index date). Six frequently prescribed ASMs with at least 1000 available patients were analyzed. Patients treated with one of six ASMs were matched to each other by propensity scores based on sex, age, and secondary diagnoses. Cox regression models were used to analyze the association between the use of ASM and LUTI risk. RESULTS: The cumulative LUTI incidence 12 months after the start of therapy was highest in patients treated with pregabalin (16.7%), followed by valproate (11.6%) and gabapentin (10.2%). A similar trend was observed for LUTI with antibiotic prescription (9.2% pregabalin, 6.8% valproate, 6.8% gabapentin). Conditional regression analyses revealed that pregabalin therapy was significantly positively associated with LUTI (HR: 1.76; 95% CI 1.29-2.39) and LUTI-based antibiotic prescription (HR: 2.16; 95% CI 1.43-3.27). Carbamazepine was associated with a significantly lower incidence of LUTI in women (HR: 0.47; 95% CI: 0.30-0.75), but not in men. No significant associations were observed for other ASMs. CONCLUSION: The present study identifies a significant positive association between ASM and LUTI incidence and antibiotic prescriptions in patients with epilepsy treated with pregabalin, whereas a protective effect was found for carbamazepine in women only. No significant associations were observed for the four remaining ASMs.

Association between contraceptive use and risk of lower urinary tract infection (LUTI): A case-control study.

AIM: The aim of this study was to analyze the association between widely used contraceptive methods and the manifestation of lower urinary tract infections (LUTI) in patients treated in gynecological practices in Germany. MATERIALS AND METHODS: This study was based on IQVIA Disease Analyzer database and includes a total of 133,638 females aged between 16 and 50 years who received an initial diagnosis of LUTI including cystitis (ICD-10: N39.0, N30.0) between January 2011 and December 2020 (index date). 1 : 1 matching of LUTI cases to non-LUTI controls was used to investigate the association between predefined criteria and LUTI. A greedy nearest neighbor propensity score method was used to balance cases and controls with respect to age, pregnancy, visit frequency during the observation period, and comorbidities including cancer, diabetes mellitus, and urolithiasis. Univariate logistic regression models were used to assess the association between contraceptive prescriptions and LUTI. RESULTS: The general use of any contraceptive method was negatively associated with subsequent LUTI. Injectable contraceptives and pills were negatively associated with LUTI manifestation. There was a significant negative association between monophasic preparations containing < 50 µg estrogen, triphasic preparations, and progestogen-only preparations and LUTI. By contrast, we found a significant positive association between emergency contraceptives and LUTI. CONCLUSION: The general application of birth control methods as well as the use of injectable contraceptives and oral contraceptives were negatively associated with LUTI manifestation. In contrast to other birth control methods, the intake of emergency contraception was positively associated with a manifestation of LUTI.

Evaluation of the representativeness of the German Oncology Dynamics dataset.

OBJECTIVES: To evaluate the representativeness of the German Oncology Dynamics (OD) dataset by comparing its projected patient population structure with that outlined in published epidemiological literature. MATERIALS AND METHODS: The OD is an international cross-sectional semi-retrospective survey collecting anonymized patient cases from a representative panel of physicians via a web-based questionnaire; the cases are quality-checked and projected to the drug-treated prevalence using physician workload information. The present study verifies the OD 2018 projected patient proportions by indication and sex against prevalence figures in IARC's Globocan and the Cancer in Germany report by the Robert Koch Institute. Additionally, age group and metastasis presence distributions in gonadotropin-releasing hormone analog (GnRHa)-treated prostate cancer patients are compared with the findings of a registry-based study: Retrospective Analysis of Patients with Prostate Cancer Initiating GnRH Agonists/Antagonists Therapy Using a German Claims Database: Epidemiological and Patient Outcomes by Hupe et al. [3]. RESULTS: The OD demonstrated a cancer type distribution similar to the comparator sources. Cancer-specific sex distribution differences could be attributed to real-world diagnosis and treatment patterns. The age group distributions of GnRH-treated prostate cancer patients did not differ significantly between the OD and the Hupe et al. [3] study according to confidence interval comparisons and a Kolmogorov-Smirnov test. CONCLUSION: Projected patient distributions for the OD Germany were similar to those documented in the published literature. The dissimilarities can be attributed to the low drug-treated prevalence of some cancer types and sex-specific diagnosis timeline differences. Further investigations are needed to verify the reliability of histological biomarker data as well as patient demographics in other countries.

p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group.

BACKGROUND: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed. OBJECTIVE: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance. STUDY DESIGN: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction. RESULTS: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53- (n=132), and p16-/p53- (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53- tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16-/p53- tumors; P<.0001) and showed lower rates of lymph-node involvement (28.0% vs 42.3% for p53+, respectively, 30.2% for p16-/p53- tumors; P=.050). Notably, 2-year-disease-free and overall survival rates were significantly different among the groups: disease-free survival, 47.1% (p53+), 60.2% (p16-/p53-), and 63.9% (p16+/p53-) (P<.001); overall survival, 70.4% (p53+), 75.4% (p16-/p53-), and 82.5% (p16+/p53-) (P=.002). In multivariate analysis, the p16+/p53- phenotype showed a consistently improved prognosis compared with the other groups (hazard ratio, 0.66; 95% confidence interval, 0.44-0.99; P=.042). CONCLUSION: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

Prevalence of and factors associated with the prescription of phytopharmaceuticals in outpatients with urinary tract infections.

AIMS: The objective of this study is to determine the prevalence of phytopharmaceutical prescription in patients with urinary tract infection (UTI) and pinpoint the factors influencing phytopharmaceutical prescription by general practitioners, urologists, and gynecologists. MATERIALS AND METHODS: This cross-sectional study was based on data from the Disease Analyzer database (IQVIA) and included patients with a diagnosis of UTI or acute cystitis in 1,132 general (GP), 238 gynecologist, and 91 urologist practices in 2019. The prevalence of phytopharmaceutical prescription was estimated, and a multivariable logistic regression model was used to study the association between predefined variables and phytopharmaceutical prescription and adjusted odds ratios (ORs) were estimated. RESULTS: In total, 83,905 individuals treated by GPs, 10,456 treated by gynecologists, and 30,637 treated by urologists were diagnosed with UTI in 2019. Of these patients, 8.4% (95% CI: 8.2 - 8.6) treated by GP, 8.5% (95% CI: 8.0 - 9.1) treated by gynecologists, and 4.8% (95% CI: 4.6 - 5.0) treated by urologists received a phytopharmaceutical prescription. Practice preference for phytopharmaceutical prescription (OR: 6.09 by GPs, OR: 2.20 by urologists, OR: 11.03 by gynecologists), female sex (OR: 2.34 by GPs, OR: 6.54 by urologists) and private health insurance (OR: 1.97 by GPs, OR: 2.33 by gynecologists, OR: 1.98 by urologists) were associated with increased odds of phytopharmaceutical prescription. CONCLUSION: Our data show that phytopharmaceuticals have a relatively low prevalence in the treatment of UTIs. Moreover, practice-related factors, concretely phytopharmaceutical preference, seem to play an important role in prescribing prevalence and should be studied in more detail in the future studies.

Gynecologists' attitudes toward and use of complementary and integrative medicine approaches: results of a national survey in Germany.

PURPOSE: Despite patients' widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals' current implementation of it in clinical routine. A national survey was conducted to assess gynecologists' attitudes to and implementation of complementary and integrative treatment approaches. METHODS: The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email. RESULTS: Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016). CONCLUSIONS: There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

Association between thyroid gland diseases and breast cancer: a case-control study.

BACKGROUND: At the present time, there is no consensus on the association between benign thyroid diseases and breast cancer (BC). Therefore, the aim of this study is to help shed some light on the association between hyperthyroidism, hypothyroidism, and thyroiditis and breast cancer risk. METHODS: Use of the Disease Analyzer database (IQVIA) enabled us to perform a retrospective case-control study of 7408 women aged between 18 and 80, who were treated for an initial breast cancer diagnosis in a general practice in the United Kingdom between 2006 and 2015 (index date). Patients with a previous cancer diagnosis and an observation time of less than 12 months prior to the index date were excluded. The control group consisted of 7408 healthy women, who were matched to cases 1:1 by age, body mass index, hormone replacement therapy, and physician. The main outcome parameters of this study were the presence of thyroid disease (hypothyroidism, hyperthyroidism, struma, and thyroiditis) and the TSH values in the two groups. A univariate logistic regression model was used to investigate the association between benign thyroid diseases, TSH values, and BC. RESULTS: The mean age was 58.4 years in both groups. We found a significant association between thyroiditis and BC (OR: 1.91, p = 0.01) and were able to refute the association between hyperthyroidism/hypothyroidism and BC. We also found that thyroid-stimulating hormone (TSH) had no significant effect on breast cancer risk. CONCLUSION: Many experimental studies suggest a link between hyperthyroidism/hypothyroidism and BC. We were able to demonstrate an epidemiological association between thyroiditis and an increased BC risk. This shows the need for close monitoring for BC in women with thyroiditis.

Fecal and urinary incontinence are major problems associated with rectal cancer.

BACKGROUND: The goal of this retrospective cohort study was to analyze the incidence of urinary incontinence (UI) and fecal incontinence (FI) within 5 years of diagnosis in patients with rectal carcinoma (RC) and within 5 years of a randomly selected visit date in non-cancer controls followed in general practices in Germany. METHODS: Patients who had received an initial RC diagnosis at one of 1262 general practices in Germany between January 2008 and December 2017 were included in this study (index date). Patients without cancer were matched (1:1) to RC patients by sex, age, index year, and practice. The main outcome of the study was the incidence of UI and FI within 5 years of RC diagnosis. RESULTS: The study included 3249 individuals with RC and 3249 individuals without cancer (mean age 66.5 years, 57.3% males). Within 5 years of the index date, 8.6% of RC patients and 1.3% of patients without cancer received a FI diagnosis, and 16.7% of RC patients and 5.3% of patients without cancer received a UI diagnosis. Overall, RC was positively associated with both FI (hazard ratio (HR) 8.39, 95% CI 5.50-12.81) and UI (HR 3.59, 95% CI 2.91-4.44). These findings were corroborated in the different age subgroups. CONCLUSION: In accordance with the literature, we confirmed that RC is significantly associated with fecal and urinary incontinence. However, it appears that the awareness of this fact needs to be improved among general practitioners since our data show lower percentages of fecal and urinary incontinence diagnoses compared with the percentages for specialized centers reported in the literature.

The usage of over-the-counter products by private insured patients in Germany - a claims data analysis with focus on complementary medicine.

BACKGROUND: An important contribution to well-being of human beings can be observed by the use of self-medication products that is reflected in the constantly growing volume of over-the-counter (OTC) drugs. The aim of the current study was to extend the measurement concept for OTCs by exploring the relevance of the peripheral assortment provided by the widely accepted framework of the Anatomical Therapeutical and Chemical (ATC) classification of the WHO. METHODS: The focus was on the prescriptions and drug-related receipts submitted by privately insured persons to 18 private health insurers (PHIs) in Germany from the year 2016. The age- and gender-specific average claims amount per risks of outpatient drug expenditure were used as weights to scale up the relative distributions of the item amounts. The ATC-classification defines the commodity groups and discriminates between the main and the peripheral assortment. A descriptive analysis assessed the OTC frequencies and sum scores of the product groups within the main and peripheral assortment whereby the study group explored and assessed the relevance of each category independently according to the OTCs and integrative medicines. RESULTS: The analysis included 22.1 Mio. packages from the main assortment and examined 10.1 Mio. packages from the peripheral assortment. The latter was examined thoroughly and the commodity groups "Pharmaceutical food products", "Medicinal products for special therapy options" and particular "Hygiene and body care products" meet the defined requirements for OTCs relevant for integrative medicines. A high proportion of OTC products from the peripheral assortment was associated with the categories "medicinal products for special therapy options". Homeopathy and anthroposophy present two special therapy options, which are relevant for the extended OTC measurement. CONCLUSIONS: The analysis of OTC drugs is feasible when the main and the peripheral assortment is available and enable to integrate about 18% of all OTCs, which are neglected by the common ATC-based approach. The presented extended approach may help to identify potential users of OTCs or people in need of OTC use. In case of the highly disputed homeopathy and anthroposophy products, more research among interactions with prescriptions drugs (Rx), nutrition's and other potentially harmful exposures is recommended.