Abstract
Background
The delivery of health services around the world faced considerable disruptions during the COVID-19 pandemic. While this has been discussed for a number of conditions in the adult ...population, related patterns have been studied less for children. In light of the detrimental effects of the pandemic, particularly for children and young people under the age of 18, it is pivotal to explore this issue further.
Methods
Based on complete national hospital discharge data available via the German National Institute for the Reimbursement of Hospitals (InEK) data browser, we compare the top 30 diagnoses for which children were hospitalised in 2019, 2020, 2021 and 2022. We analyse the development of monthly admissions between January 2019 and December 2022 for three tracers of variable time-sensitivity: acute lymphoblastic leukaemia (ALL), appendicitis/appendectomy and tonsillectomy/adenoidectomy.
Results
Compared to 2019, total admissions were approximately 20% lower in 2020 and 2021, and 13% lower in 2022. The composition of the most frequent principal diagnoses remained similar across years, although changes in rank were observed. Decreases were observed in 2020 for respiratory and gastrointestinal infections, with cases increasing again in 2021. The number of ALL admissions showed an upward trend and a periodicity prima vista unrelated to pandemic factors. Appendicitis admissions decreased by about 9% in 2020 and a further 8% in 2021 and 4% in 2022, while tonsillectomies/adenoidectomies decreased by more than 40% in 2020 and a further 32% in 2021 before increasing in 2022; for these tracers, monthly changes are in line with pandemic waves.
Conclusions
Hospital care for critical and urgent conditions among patients under the age of 18 was largely upheld in Germany during the COVID-19 pandemic, potentially at the expense of elective treatments. There is an alignment between observed variations in hospitalisations and pandemic mitigation measures, possibly also reflecting changes in demand. This study highlights the need for comprehensive, intersectoral data that would be necessary to better understand changing demand, unmet need/foregone care and shifts from inpatient to outpatient care, as well as their link to patient outcomes and health care efficiency.
To describe the monthly distribution of COVID-19 hospitalisations, deaths and case-fatality rates (CFR) in Lombardy (Italy) throughout 2020.
We analysed de-identified hospitalisation data comprising ...all COVID-19-related admissions from 1 February 2020 to 31 December 2020. The overall survival (OS) from time of first hospitalisation was estimated using the Kaplan-Meier method. We estimated monthly CFRs and performed Cox regression models to measure the effects of potential predictors on OS.
Hospitalisation and death peaks occurred in March and November 2020. Patients aged ≥70 years had an up to 180 times higher risk of dying compared to younger patients 70-80: HR 58.10 (39.14-86.22); 80-90: 106.68 (71.01-160.27); ≥90: 180.96 (118.80-275.64). Risk of death was higher in patients with one or more comorbidities 1: HR 1.27 (95% CI 1.20-1.35); 2: 1.44 (1.33-1.55); ≥3: 1.73 (1.58-1.90) and in those with specific conditions (hypertension, diabetes).
Our data sheds light on the Italian pandemic scenario, uncovering mechanisms and gaps at regional health system level and, on a larger scale, adding to the body of knowledge needed to inform effective health service planning, delivery, and preparedness in times of crisis.
Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated ...the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.
COVID-19 is a novel infectious disease which has rapidly spread around the globe, disrupting several aspects of public life over the past year. After numerous infection clusters emerged among ...travelers hosted in ski resorts in early 2020, several European countries closed ski areas. These measures were mostly upheld throughout the 2020 and 2021 winter season, generating significant economic loss for mountain communities. The aim of this rapid systematic review was to explore the association between recreational skiing and the spread of COVID-19. This review was conducted according to the WHO practical guidelines on rapid reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Scopus, MedRxiv and Promed-mail were screened to identify relevant scientific and grey literature published since the emergence of COVID-19. Among the 11 articles included, seven focused on cases recorded during the first epidemic wave, when COVID-19 containment measures were not yet mandatory. Most infection clusters could be directly linked to public gatherings which took place without the enforcement of restrictions. There is currently no evidence to suggest an association between COVID-19 spread and recreational skiing. It may be reasonable to consider the reopening of ski areas in compliance with strict rules and preventive measures.
IntroductionCausal methods have been adopted and adapted across health disciplines, particularly for the analysis of single studies. However, the sample sizes necessary to best inform decision-making ...are often not attainable with single studies, making pooled individual-level data analysis invaluable for public health efforts. Researchers commonly implement causal methods prevailing in their home disciplines, and how these are selected, evaluated, implemented and reported may vary widely. To our knowledge, no article has yet evaluated trends in the implementation and reporting of causal methods in studies leveraging individual-level data pooled from several studies. We undertake this review to uncover patterns in the implementation and reporting of causal methods used across disciplines in research focused on health outcomes. We will investigate variations in methods to infer causality used across disciplines, time and geography and identify gaps in reporting of methods to inform the development of reporting standards and the conversation required to effect change.Methods and analysisWe will search four databases (EBSCO, Embase, PubMed, Web of Science) using a search strategy developed with librarians from three universities (Heidelberg University, Harvard University, and University of California, San Francisco). The search strategy includes terms such as ‘pool*’, ‘harmoniz*’, ‘cohort*’, ‘observational’, variations on ‘individual-level data’. Four reviewers will independently screen articles using Covidence and extract data from included articles. The extracted data will be analysed descriptively in tables and graphically to reveal the pattern in methods implementation and reporting. This protocol has been registered with PROSPERO (CRD42020143148).Ethics and disseminationNo ethical approval was required as only publicly available data were used. The results will be submitted as a manuscript to a peer-reviewed journal, disseminated in conferences if relevant, and published as part of doctoral dissertations in Global Health at the Heidelberg University Hospital.
Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of ...patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript.
The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856.
Venous thromboembolism (VTE) is a known complication in children with leukemia, with prevalence in acute lymphoblastic leukemia (ALL) reported as high as 37% (Mitchell, et al, Cancer, 2003). ...Indwelling catheters, hyperviscosity, mediastinal masses, and medications such as asparaginase, can all contribute to increased VTE risk. In addition to national interest in preventing VTE in hospitalized children, decreasing risk of VTE in children with cancer is of great importance to pediatric hematologist/oncologists. The International Society of Hemostasis and Thrombosis released a guidance statement (Tullius, et al, JTH, 2017) that suggested considering thromboprophylaxis on a case-by-case basis for children with cancer and multiple VTE risk factors, and suggested discontinuing anticoagulant prophylaxis when predisposing conditions resolve. Children with leukemia certainly may have multiple risk factors and therefore deserve consideration for prophylaxis. The Children's Oncology Group is currently conducting a clinical trial studying thromboprophylaxis during induction for ALL. Given the importance of reducing VTE and the interest in thromboprophylaxis, we sought to assess practitioners' practices regarding thromboprophylaxis in children with leukemia.
We performed a cross sectional, anonymous survey of pediatric members of VENUS (the VTE Network of the Hemostasis and Thrombosis Research Society) and ASH (the American Society of Hematology) using Qualtrics, a secure online survey tool. Responses were excluded if physicians answered no to either of 2 screening questions (related to clinical practice and board certification/eligibility), or if no questions were answered after screening. A gift card incentive was offered anonymously. Institutional IRBs approved this study.
870 surveys were distributed, with a response rate of 17.7%; after exclusions, a total of 142 surveys were included. Demographics were well balanced regarding size of program and years in practice. When asked about which anticoagulant agents may be used for thromboprophylaxis (n=36), 92% of those responding reported using enoxaparin (Table 1). In addition, 36% use Apixaban and 14% use Rivaroxaban.
When asked if they ever provide primary VTE prophylaxis to children with leukemia (n=127), 71% said no, while 29% answered yes (Table 1). When asked in what scenarios primary prophylaxis was used, the most common answer was in leukemia patients with a known inherited thrombophilia (57%). Also common were children with mediastinal masses with vessel compression, and children enrolled on the COG prophylaxis study. Some additional scenarios offered were AYA patients, and those with additional risk factors, such as obesity and immobility. When asked about duration of primary prophylaxis (n=36), the most common times for discontinuing therapy were resolution of mediastinal mass and/or vessel compression (58%), end of all asparaginase therapy (50%), and until the central line is removed (42%). A smaller number of physicians (22%) would consider continuing anticoagulant prophylaxis until the end of all cancer chemotherapy. When questioned about secondary prophylaxis following VTE (n=127), 8% of respondents never provide post-VTE prophylaxis, 11% always give post-VTE prophylaxis, and 81% used post-VTE prophylaxis in certain cases (Table 1.) The most common stopping point for secondary prophylaxis (n=116) was after central line removal (55%), followed by completion of all asparaginase therapy (41%).
Our study is limited by a low response rate. Due to technical issues, we had missing data for many questions and could not obtain free-text answers for some of the prophylaxis questions, limiting full data acquisition. Despite these issues, our results provide some insights into current practices of pediatric hematologist/oncologists. This study shows that many physicians are not utilizing primary anticoagulant prophylaxis in their pediatric leukemia patients, despite the high-risk nature of these patients, possibly trying to balance bleeding risk due to thrombocytopenia. Duration of anticoagulant therapy varies, and it is likely that there are no clear definitions regarding resolution of predisposing factors. Given their unique set of risk factors, and the potential morbidity associated with VTE, further study of VTE prophylaxis is essential for development of pediatric leukemia-specific guidelines.
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Cooley:off-label: Other: drug use. Acharya:Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.
We surveyed physicians on which anticoagulants they use in their pediatric leukemia patients and the majority of drugs offered as answer choices are technically off-label.
The development of venous thromboembolism (VTE) is a known complication occurring in children with leukemia with a reported incidence ranging from 1 to 37% (Ghanem, et al, Pediatric Blood & Cancer, ...2017) and can be a source of significant morbidity. Known risk factors for VTE include central venous catheter (CVC) use, thrombophilia, and certain medications, such as asparaginase (Caruso, et al, Blood, 2006.) Despite the known occurrence of VTE in this population, there are no leukemia-specific guidelines for VTE management. Anticoagulant use in children with frequent periods of thrombocytopenia and coagulopathy is not risk free. Various elements of management lack standardization and consensus among practitioners. Given that the majority of pediatric leukemia patients are treated according to standardized protocols, it may be beneficial to standardize anticoagulation care guidelines. Therefore, the primary objective of this study was to assess current practices regarding the management of VTE in the pediatric leukemia population.
We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology (ASH) who self-identified as focusing in pediatric hematology or pediatric hematology/oncology, and the pediatric subcommittee of VENUS (VTE Network of the Hemostasis and Thrombosis Research Society) using Qualtrics, a secure online survey tool. Survey items included questions on demographics and clinical practice. Respondents were excluded if they were not board certified/eligible, if they did not participate in patient care, or if they did not answer survey research questions. A $25 gift card incentive was offered anonymously. This study was approved by both the Weill Cornell Medicine and Northwell Health IRBs.
Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Twelve surveys were excluded, leaving 142 surveys for final analysis. There was even distribution of years in practice and size of clinical program among respondents (Figure 1A). Most respondents identified as being in hematology or combined practice.
50% of responding physicians (n=136) reported treating CVC-associated VTE for 3 months. 92% of respondents (n=138) report repeating imaging of the VTE with 58% (n=124) repeating at 6 weeks, and 31% at 3 months. 40% of respondents (n=131) treat cerebral venous sinus thrombosis (CVST) for 3 months, followed by 24% treating for 6 months. 95% of respondents (n=131) repeat imaging for CVST and of these individuals, 40% repeat imaging at 6 weeks followed by 50% at 3 months.
The most frequently utilized anticoagulant class was heparins (n=140); respondents also reported using the direct Xa inhibitors Rivaroxaban (21%) and Apixaban (14%). Within the group utilizing direct Xa inhibitors, those in practice the longest (≥16 years) had the highest percentage of use (Figure 1B.) When asked at what platelet counts they hold therapeutic anticoagulation (n=140), 39% of respondents chose 50 x 109/L, 33% chose 30 x 109/L, and 16% chose 20 x 109/L. One person chose 100, x 109/L, 11% said they did not hold anticoagulation for thrombocytopenia, and 2 respondents gave platelet transfusions rather than hold anticoagulation (one at a cutoff below 30 x 109/L and one below 50 x 109/L). While no significant associations were seen, the highest percentage among individual groups using a platelet cutoff of less than 50 x 109/L were among those in practice longest, and those in the largest centers (Figure 1C).
The results of this survey revealed variation in practice among practitioners regarding VTE management and prevention. Despite the lack of data in this population, a number of physicians are using direct Xa inhibitors in children with leukemia for anticoagulation. Imaging is being done earlier than treatment is being discontinued, potentially implying it is being used to monitor for progression, rather than help guide duration of therapy. Our survey had some limitations, including the low response rate and missing data for questions, which may be due to electronic data collection errors or respondent choice. Recent ASH guidelines endorsed by the Children's Oncology Group propose limited general guidelines and do not consider a cancer patient's unique VTE risk profile. Given the variation seen, multi-center, prospective clinical trials are urgently needed for developing consensus guidelines for the management of VTE in children with leukemia.
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Cooley:off-label: Other: drug use. Acharya:Takeda: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees.
Anticoagulations that will be discussed are off-label in children.
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