The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Illness perception and family resilience in gynaecologic cancer patients: A study on the mediating role of hope.

OBJECTIVE: To investigate the level of family resilience among patients with gynaecologic cancer and explore hope as a mediator between perceptions of illness and family resilience. DESIGN: A cross-sectional study. METHOD: From May to October 2022, researchers used convenience sampling to survey 320 patients with gynaecological cancer at a level 3A hospital in Jinan City. The study instruments included the General Information Questionnaire, Family Hardiness Index, Brief Illness Perception Questionnaire, and Herth Hope Index. SPSS 26.0 was used to analyse the mediation effect of hope. RESULTS: The mean score for family resilience was 55.86 ± 8.62. Illness perception was negatively associated with family resilience, while hope was positively associated with it. Additionally, hope mediated the relationship between illness perception and family resilience. CONCLUSION: There is considerable room for improvement in family resilience among patients with gynaecologic cancer. Interventions aimed at increasing hope can enhance family resilience. IMPACT: Healthcare providers can boost family resilience by fostering hope in patients, thereby promoting effective coping and adaptation to cancer. PATIENT OR PUBLIC CONTRIBUTION: Patients primarily completed the questionnaires, providing insights into the factors that hindered and facilitated the development of family resilience. These findings were communicated to caregivers for further understanding and action.

Early oral hydration on demand in postanesthesia care unit effectively relieves postoperative thirst in patients after gynecological laparoscopy: a prospective randomized controlled trial.

BACKGROUND: Postoperative thirst is one of the most intense, common and easily ignored subjective discomforts in patients after gynecological surgery. This study aimed to investigate whether early oral hydration on demand in the postanesthesia care unit (PACU) after gynecological laparoscopy under general anesthesia can appease postoperative thirst and increase patient comfort. METHODS: Participants were randomized into the intervention and control groups. Patients in the intervention group were allowed to achieve early oral hydration on demand in the PACU if they were evaluated as fully conscious, with stable vital signs, grade 5 muscle strength, and well-recovered cough and swallowing reflex. However, the total amount of water intake throughout the entire study should not exceed 0.5mL/kg. During the study, the frequency of water intake, the total amount of water intake and adverse events were accurately recorded. The control group was managed according to the routine procedures and began to drink water 2 h after anesthesia. The intensity of thirst and subjective comfort in patients were assessed using the visual analog scale (VAS) when they entered and left the PACU. RESULTS: No statistically significant differences were identified in age, height, weight, body mass index, pre-operative fasting time, duration of surgery, intraoperative fluid intake, intraoperative blood loss, intraoperative urine volume, and thirst intensity and subjective comfort scores between the groups before intervention (P > 0.05). After intervention, the VAS score for thirst intensity in the intervention group significantly decreased (P < 0.05), and the VAS score for subjective comfort in the intervention group significantly increased (P < 0.05). No adverse events were detected in both groups during the entire study. CONCLUSION: Early oral hydration on demand in the PACU can safely and effectively relieve postoperative thirst in patients, and improve patient comfort after gynecological laparoscopy. TRIAL REGISTRATION: This single-center, prospective, randomized controlled trial was registered at the Chinese Clinical Trial Center on April 27, 2023. The registration number of this study is ChiCTR2300070985.

Management of Malignant Bowel Obstruction in Patients with Gynaecological Cancer: A Systematic Review.

Objectives: This systematic review aimed to evaluate current surgical and non-surgical management strategies for malignant bowel obstruction (MBO) in patients with gynaecological cancer. Methods: Comprehensive literature searches were conducted across MEDLINE, Embase, CENTRAL, and Scopus, without restrictions on language or publication date. Following the removal of duplicates, 4866 articles were screened, with 34 meeting the inclusion criteria. Results: Surgical intervention remains the definitive treatment for MBO, offering longer symptom-free periods and improved survival, particularly when conservative methods fail. However, the selection of surgical candidates is crucial due to the high risk of morbidity and the potential for significant complications. Non-surgical treatments, such as the use of Gastrografin, Octreotide, and Dexamethasone, along with invasive procedures like nasogastric tubing, percutaneous gastrostomy, and stent placement, offer varying degrees of symptom relief and are often considered when surgery is not feasible. Conclusions: In this article we provide a potential therapeutic algorithm for the management of patients with MBO. This review underscores the urgent need for high-quality research to develop clear, evidence-based guidelines for MBO management in patients with gynaecologic cancer. Establishing standardised protocols will improve patient outcomes by aiding clinicians in making informed, individualised treatment decisions.

Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

Prevalence of hysterectomy and associated factors in Brazilian women aged 50 and older: findings from the Brazilian Longitudinal Study of Ageing (ELSI-Brazil).

BACKGROUND: Hysterectomy is a gynaecological surgical procedure in which the uterus is removed as a treatment for both malignant and benign gynaecological diseases. A hysterectomy is also performed to minimise risks in women with problems related to the uterus. This study aimed to estimate the prevalence of reported hysterectomy and associated risk factors in Brazilian women aged 50 and older. METHODS: A cross-sectional study using data from the Brazilian Longitudinal Study of Ageing (ELSI-Brazil) was conducted. A total of 5,293 women aged 50 and over who participated in the ELSI-Brazil study in 2015 and 2016 were included. The prevalence rate of hysterectomy was estimated and the main reasons for performing the surgery were identified. The bivariate analyses utilised the chi-square test, while multivariate analyses employed Poisson regression with a robust estimator. RESULTS: The reported prevalence of hysterectomy was 17.8%. The most prevalent reason for the surgery was the presence of uterine myoma. Significant and independent associations were observed in women aged 63 and older, married, having undergone preventive exams, hormonal treatment, had up to three deliveries and having a private health plan. CONCLUSION: The main objective of the study was achieved. The prevalence of hysterectomy in Brazilian women aged 50 and older was 17.8%. Significant associations were observed with participants' sociodemographic and clinical characteristics reinforcing the importance of considering the reproductive characteristics of women as indicators of health status.

Patient care and access to clinical trials in gynaecological oncology: global implications of the early phase of the COVID-19 pandemic.

PURPOSE: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation. METHODS: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey. RESULTS: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage. CONCLUSION: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials.

Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy.

Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms. Women with an increased inherited risk for EOC are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO), which decreases their EOC risk by 96% when performed within guideline ages. However, it also induces premature menopause, which has harmful consequences. There is compelling evidence that the majority of EOCs originate in the fallopian tube. Therefore, a risk-reducing salpingectomy with delayed oophorectomy (RRS with DO) has gained interest as an alternative strategy. Previous studies have shown that this alternative strategy has a positive effect on menopause-related quality of life and sexual health when compared to the standard RRSO. It is hypothesized that the alternative strategy is non-inferior to the standard RRSO with respect to oncological safety (EOC incidence). Three prospective studies are currently including patients to compare the safety and/or quality of life of the two distinct strategies. In this article we discuss the background, opportunities, and challenges of the current and alternative strategy.

Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool.

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in the female reproductive system. It is the leading cause of death among gynecological cancers owing to its metastasis. Since its preliminary disease symptoms are lacking, it is imperative to develop early diagnostic biomarkers to aid in treatment optimization and personalization. In this vein, microRNAs, which are short sequence non-coding molecules, displayed great potential as highly specific and sensitive biomarker. miRNAs have been extensively advocated and proven to serve an instrumental part in the clinical management of cancer, especially ovarian cancer, by promoting the cancer cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis of cancer cells, chemosensitivity and resistance and disease therapy. Here, we cover our present comprehension of the most up-to-date microRNA-based approaches to detect ovarian cancer, as well as current diagnostic and treatment strategies, the role of microRNAs as oncogenes or tumor suppressor genes, and their significance in ovarian cancer progression, prognosis, and therapy.

Incorporating low haemoglobin into a risk prediction model for conversion in minimally invasive gynaecologic oncology surgeries.

BACKGROUND: A well-known complication of laparoscopic management of gynaecologic masses and cancers is the need to perform an intraoperative conversion to laparotomy. The purpose of this study was to identify novel patient risk factors for conversion from minimally invasive to open surgeries for gynaecologic oncology operations. METHODS: This was a retrospective cohort study of 1356 patients ≥18 years of age who underwent surgeries for gynaecologic masses or malignancies between February 2015 and May 2020 at a single academic medical centre. Multivariable logistic regression was used to study the effects of older age, higher body mass index (BMI), higher American Society of Anaesthesiologist (ASA) physical status, and lower preoperative haemoglobin (Hb) on odds of converting from minimally invasive to open surgery. Receiver operating characteristic (ROC) curve analysis assessed the discriminatory ability of a risk prediction model for conversion. RESULTS: A total of 704 planned minimally invasive surgeries were included with an overall conversion rate of 6.1% (43/704). Preoperative Hb was lowest for conversion cases, compared to minimally invasive and open cases (11.6 ± 1.9 vs 12.8 ± 1.5 vs 11.8 ± 1.9 g/dL, p<.001). Patients with preoperative Hb <10 g/dL had an adjusted odds ratio (OR) of 3.94 (CI: 1.65-9.41, p=.002) for conversion while patients with BMI ≥30 kg/m2 had an adjusted OR of 2.86 (CI: 1.50-5.46, p=.001) for conversion. ROC curve analysis using predictive variables of age >50 years, BMI ≥30 kg/m2, ASA physical status >2, and preoperative haemoglobin <10 g/dL resulted in an area under the ROC curve of 0.71. Patients with 2 or more risk factors were at highest risk of requiring an intraoperative conversion (12.0%). CONCLUSIONS: Lower preoperative haemoglobin is a novel risk factor for conversion from minimally invasive to open gynaecologic oncology surgeries and stratifying patients based on conversion risk may be helpful for preoperative planning.

Minimally invasive surgery for management of gynaecologic masses (masses that affect the female reproductive organs) is often preferred over more invasive surgery, because it involves smaller surgical incisions and can have overall better recovery time. However, one unwanted complication of minimally invasive surgery is the need to unexpectedly convert the surgery to an open surgery, which entails a larger incision and is a higher risk procedure. In our study, we aimed to find patient characteristics that are associated with higher risk of converting a minimally invasive surgery to an open surgery. Our study identified that lower levels of preoperative haemoglobin, the protein that carries oxygen within red blood cells, is correlated with higher risk for conversion. This new risk factor was used with other known risk factors, including having higher age, higher body mass index, and higher baseline medical complexity to create a model to help surgical teams identify high risk patients for conversion. This model may be useful for surgical planning before and during the operation to improve patient outcomes.

Entrapped by pain: The diagnosis and management of endometriosis affecting somatic nerves.

Somatic nerve entrapment caused by endometriosis is an underrecognized and often misdiagnosed issue that leads to many women suffering unnecessarily. While the classic symptoms of endometriosis are well-known to the gynaecologic surgeon, the dermatomal-type pain caused by endometriosis impacting neural structures is not within gynecologic day-to-day practice, which often complicates diagnosis and delays treatment. A thorough understanding of pelvic neuroanatomy and a neuropelveologic approach is required for accurate assessments of patients with endometriosis and nerve entrapment. Magnetic resonance imaging is the preferred imaging modality for this presentation of endometriosis. Surgical management with laparoscopic or robotic-assisted techniques is the preferred approach to treatment, with excellent long-term results reported after nerve detrapment and endometriosis excision. The review calls for increased awareness and education on the links between endometriosis and the nervous system, advocating for patient-centered care and further research to refine the diagnosis and treatment of this challenging condition.

Late-Stage Ovarian Cancer With Systemic Multiple Metastases Shows Marked Shrinkage Using a Combination of Wilms' Tumor Antigen 1 (WT1) Dendritic Cell Vaccine, Natural Killer (NK) Cell Therapy, and Nivolumab.

A patient with bilateral ovarian cancer, peritoneal dissemination, and multiple liver and lung metastases was found with a sudden accumulation of ascites six months after delivery. Chemotherapy was started, but the prognosis was judged to be poor, so immuno-cell therapy was combined with chemotherapy. After multiple cycles of Wilms' tumor antigen 1 (WT1) dendritic cell vaccine therapy and highly activated natural killer (NK) cell therapy, the patient showed a disappearance of ascites and a remarkable reduction of multiple cancers in the whole body. Furthermore, there were no side effects other than reactive fever caused by the administration of immune cells, and no damage to the patient's body was observed. This case suggests that not only the combined effects of chemotherapy and immunotherapy but also the combined use of various types of immuno-cell therapy may provide beneficial clinical effects in patients with extremely poor prognoses and few options for standard treatment.

HER2 evaluation for clinical decision making in human solid tumours: pearls and pitfalls.

The significant clinical benefits of human epidermal growth factor receptor 2 (HER2)-targeted therapeutic agents have revolutionized the clinical treatment landscape in a variety of human solid tumours. Accordingly, accurate evaluation of HER2 status in these different tumour types is critical for clinical decision making to select appropriate patients who may benefit from life-saving HER2-targeted therapies. HER2 biomarker scoring criteria is different in different organ systems, and close adherence to the corresponding HER2 biomarker testing guidelines and their updates, if available, is essential for accurate evaluation. In addition, knowing the unusual patterns of HER2 expression is also important to avoid inaccurate evaluation. In this review, we discuss the key considerations when evaluating HER2 status in solid tumours for clinical decision making, including tissue handling and preparation for HER2 biomarker testing, as well as pathologist's readout of HER2 testing results in breast carcinomas, gastroesophageal adenocarcinomas, colorectal adenocarcinomas, gynaecologic carcinomas, and non-small cell lung carcinomas.

Enhanced recovery after surgery (ERAS) for deep infiltrating endometriosis surgery: Experience of a French center.

OBJECTIVE: The objective of the study was to evaluate the implementation of an ERAS programme for deep pelvic endometriosis (DPE) surgery in terms of length of stay (LOS), postoperative complications (POC) and rehospitalisation rate. METHODS: This was a comparative retrospective monocentric study in the Gynaecologic Department of the La Conception Hospital in Marseille, France. We compared a 'conventional' group, with classic perioperative management corresponding to patients undergoing DPE surgery between April 8, 2014 and January 23, 2018, and an 'ERAS' group after setting up the ERAS protocol from February 6, 2018 to March 6, 2020. RESULTS: A total of 101 patients with DPE surgery were included, with 39 in the conventional group and 53 in the ERAS group. The LOS decreased by 1.91 days (p < 0.001). During the 45 postoperative days, no difference was found in rehospitalised rate (p = 1). The POC rate was 15/39 (38.5 %) in the conventional group and 12/53 (22.6 %) in the ERAS group (p = 0.1). CONCLUSION: The implementation of an ERAS programme for DPE surgery is an effective strategy because it can reduce the LOS without increasing the POC rate.

Salpingo-Oophorectomy During Non-Descent Vaginal Hysterectomy Using the Paily Vaginal Oophorectomy Clamp.

We conducted a 6-year prospective surgical case series study at a tertiary care centre in South India to evaluate the safety and efficacy of the novel Paily Vaginal Oophorectomy Clamp and its unique application technique during non-descent vaginal hysterectomy requiring salpingo-oophorectomy. The Paily Vaginal Oophorectomy Clamp's reversed blade design allows direct and secure grasping of the infundibulopelvic ligament as there is no intervening tissue near the joint, reducing the risk of slippage. In contrast, while using conventional clamps such as Heaney's, infundibulopelvic slippage occurs due to the presence of tissue between blades near the joint. A demonstration video is provided (Video).

Gynaecological cancer incidence and mortality trends in a Brazilian State with medium human development index: A 22-year analysis.

OBJECTIVE: This study aimed to analyse trends in incidence and mortality rates of gynaecological cancer (GC) in Sergipe, a medium Human Development Index (HDI) state in northeastern Brazil during 1996-2017. METHODS: Data were obtained from the Population-based Cancer Registry of Aracaju and Brazilian Mortality Information System database. We included vulvar (VUC), vaginal (VAC), cervical (CC), uterine (UC; C54-C55), ovarian (OC), placental (PC), and unspecified female genital organ cancers. Crude rates, and age-standardised incidence and mortality rates (ASIR and ASMR, respectively) were calculated using a denominator of 100,000 women. We assessed changes in trends using the annual percentage change (APC) and the average APC (AAPC), using the Joinpoint Regression Program. RESULTS: From 1996-2017, GC ASIR exhibited a declining trend (AAPC: -3.1), while ASMR increased (AAPC: 2.1). CC had the highest ASIR and ASMR over the years, ranging from 11.6 to 34.3 cases and 4.2-9.0 deaths per 100,000, respectively. Annual decreases in ASIR were observed for CC (AAPC: -5.2) and VAC (AAPC: -5.5). OC saw an increase in mortality rates (AAPC: 1.9; 1996-2017), and CC experienced an increase during 1996-2003 (APC: 6.9). VUC displayed a substantial rise in ASMR from 2001 to 2009 (APC: 27.1), followed by a decrease (APC: -11.3). An increase in mortality trends for UC was observed during 1996-2004 (APC: 10.0), while its ASIR remained relatively unchanged over the years. CONCLUSION: While overall GC incidence trends declined, mortality rates either increased or failed to decrease significantly. Therefore, additional efforts are required to enhance prevention, diagnosis, and treatment strategies, aimed at reducing and managing the burden of GC in the future.

Gynaecologic and breast cancers in women living with HIV in South Africa: A record linkage study.

Breast and gynaecologic cancers account for approximately half of all cancers diagnosed amongst women in South Africa, many of whom also live with HIV. We aimed to determine the incidence of and risk factors for developing breast and gynaecologic cancers in women living with HIV (WLHIV) in South Africa. This is a longitudinal analysis of the South African HIV Cancer Match study including women aged ≥15 years with two or more HIV-related laboratory tests. We used Cox proportional hazard models to determine the association of Human Papilloma Virus (HPV)-related and hormone-related gynaecologic cancer with patient- and municipal-level characteristics. From 3 447 908 women and 10.5 million years of follow-up, we identified 11 384 incident and 7612 prevalent gynaecologic and breast cancers. The overall crude incidence rate was 108/1 00 000 person-years (pyears) (95% confidence interval [CI]: 106-110), with the highest incidence observed for cervical cancer (70/1 00 000 pyears; 95% CI: 68.5-71.7). Low CD4 cell counts and high HIV RNA viral loads increased the risk of cervical and other HPV-related cancers. Age was associated with both HPV-related and hormone-related cancers. Women accessing health facilities in high socioeconomic position (SEP) municipalities were more likely to be diagnosed with HPV-related cancers and breast cancer than women accessing care in low SEP municipalities. It is important to improve the immunologic status of WLHIV as part of cancer prevention strategies in WLHIV. Cancer prevention and early detection programmes should be tailored to the needs of women ageing with HIV. In addition, SEP disparities in cancer diagnostic services have to be addressed.

Gynaecologists' perceptions of outpatient gynaecologic and obstetric care in Germany during the COVID-19 pandemic.

The measures taken to contain the COVID-19 pandemic had a major impact on society, affecting medical care as well as the utilization of medical services. We aimed to identify pandemic-related changes in gynaecologic/obstetric care through the personal experience of practitioners in the outpatient sector in Germany. Three consecutive anonymous online surveys of practising gynaecologists were conducted during the pandemic (07-09/2020, 11-12/2020 and 09-11/2021). Appointment management, medical supply and patients' demand as well as concomitant circumstances were queried. Data from 860 (393, 262 and 205 from the first, second and third surveys, respectively) respondents were analysed. At the peak of the first COVID-19 wave, more than 50% of the gynaecologists surveyed had cancelled cancer screening appointments. There was a significant association between fear of self-infection and cancellation of cancer screening appointments (p = 0.006). An increase in domestic violence was reported by 13%, an increase in obesity by 67% and more advanced tumours due to delayed screening by 24% of respondents. Primary gynaecological oncological prevention was reduced in supply and demand during the COVID-19 pandemic, and this shortfall should be addressed in future similar situations. Prenatal care has been offered continuously since the start of the pandemic in Germany.