Impact of the COVID-19 Pandemic on Colorectal Cancer Care in the Netherlands: A Population-based Study

Contains fulltext : 283493.pdf (Publisher’s version ) (Open Access)INTRODUCTION: The COVID-19 pandemic disrupted health care services worldwide. In the Netherlands, the first confirmed COVID-19 infection was on February 27, 2020. We aimed to investigate the impact of the pandemic on colorectal cancer care in the Netherlands. METHODS: Colorectal cancer patients who were diagnosed in 25 hospitals in weeks 2 to 26 of the year 2020 were selected from the Netherlands Cancer Registry (NCR) and divided in 4 periods. The average number of patients treated per type of initial treatment was analyzed by the Mantel-Haenszel test adjusted for age. Median time between diagnosis and treatment and between (neo)adjuvant therapy and surgery were analyzed by the Mann Whitney test. Percentages of (acute) resection, stoma and (neo)adjuvant therapy were compared using the Chi-squared test. RESULTS: In total, 1,653 patients were included. The patient population changed during the COVID-19 pandemic regarding higher stage and more clinical presentation with ileus at time of diagnosis. Slight changes were found regarding type of initial treatment. Median time between diagnosis and treatment decreased on average by 4.5 days during the pandemic. The proportion of colon cancer patients receiving a stoma significantly increased with 6.5% during the pandemic. No differences were found in resection rate and treatment with (neo)adjuvant therapy. CONCLUSION: Despite the disruptive impact of the COVID-19 pandemic on global health care, the impact on colorectal cancer care in the Netherlands was limited

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care

Acknowledgements The study sponsor was the General Practitioners Research Institute; data collection and analysis were performed by General Practitioners Research Institute. Boehringer Ingelheim was the funding and scientific partner. The members of the PIFotal study group would like to acknowledge Dr. Jaco Voorham from Data to Insights Research Solutions for his assistance with the statistical analyses, Dr Wilma Zijlema for her assistance with the review, drafting and editing of the paper, and Dr. Hans Wouters for his contribution to the project administration in the initial phase of the project. They would also like to thank all contributing researchers: Maria João Barbosa, Ana Margarida Cruz, Liliana Silva, Duarte Araújo, Eurico Silva, Daniel Castro, João Ramires, Ana Fernandes, Catarina Carvalho, Raquel Castro, Jerzy Zientek, Ewa Pasko, Witold Drzastwa, Tomasz Kachel, Kornelia Ciekalska, Krzysztof Wytrychowski, Bernard Panaszek, Krzysztof Kowal, Ebian Brill, Willemien Feenstra, Geert Struik, Hans Schuurman, Mariette van Oostrum, Hennie Holwerda Meekma, Boudewijn Dierick, George Amofa, Esther Kuipers, Lennard Ringnalda, Boris Tyndall, Mark Drenth, Peter Mast, Hilbert Talsma, Raoul Wolfs, Cobie Hoogeboom, Hanneke van Andel, Paul Stoutenberg, Nancy van de Laak, Tessa Hillaert, Laura Holtzer, Natascha Fehrmann, Anniek Makkinga – Maassen van den Brink, Annemarie Hilbink, Erik Feenstra, Murat Tek, Sabrina Burer, Jan van Ginkel, Rinze Boersma, Alyssa Bonger, Miguel Roman Rodriguez, Marina García Pardo, Alejandra Valero Suau, Laura López Velasco, Cecilia Amato, Francisco Palmer Simó, Alberto Abenza, Rosa Llull Vila, Bartolomé Llompart Van Belzen, Silvia Jimeno Martínez, Francesc Moranta Ribas, Margarita Perelló Oliver, Yolanda Gómez López, Patricia Ibañez Gómez, María Nieves Mendieta Lagos, Laura Bueno López, Virginia María Mirabal Sánchez, Ana Delia Rodríguez Delgado, Nils Fischer, Alicia González Sansó, Nayra Ramírez Mendoza, Valeria Gazzaneo, Paula Merced Guillama Rodríguez, Virginia Naranjo Guerrero, Jose Angel Suarez Caballero, Isidoro Souto Bethencourt, Juan R. Dominguez Beatell, Elena Vanesa Rojas Manrique, Maria Jose Sanz Orejas, Cary Perez Lorenzo, Jesús Antonio Pérez Jiménez, Silvia 480 Lara Afonso Trujillo, Bartolomé Dominguez Del Río Boada, Stavroula Papageorgakopoulou, Eleytheria Vakouti, Claire Gkatzoudi, Thodoris Krasanakis, Dimitris Kounalakis , Izoldi Bouloukaki , Nikolaos Tsakountakis, Emmanouela Chronaki, Katherine Mary Borg and Kamila Abutalieva for their time and efforts to perform the study measurements and complete patient inclusion, even in the challenging times of the pandemic. Finally, they would like to thank the participants who generously gave their time to participate in the study.Peer reviewedPublisher PD

Sufficient inspiratory effort for a dry powder inhaler - do we have to measure it, or can we observe it? : Post hoc analysis of the PIFotal study.

Peer reviewedPostprin

Suboptimal Peak Inspiratory Flow and Critical Inhalation Errors are Associated with Higher COPD-Related Healthcare Costs

Purpose: To assess the relationship between suboptimal Peak Inspiratory Flow (sPIF), inhalation technique errors, and non-adherence, with Healthcare Resource Utilisation (HCRU) in Chronic Obstructive Pulmonary Disease (COPD) patients receiving maintenance therapy via a Dry Powder Inhaler (DPI). Patients and methods: The cross-sectional, multi-country PIFotal study included 1434 COPD patients (≥40 years) using a DPI for maintenance therapy. PIF was measured with the In-Check DIAL G16, and sPIF was defined as a typical PIF lower than required for the device. Inhalation technique was assessed by standardised evaluation of video recordings and grouped into 10 steps. Patients completed the "Test of Adherence to Inhalers" questionnaire. HCRU was operationalised as COPD-related costs for primary healthcare, secondary healthcare, medication, and total COPD-related costs in a 1-year period. Results: Participants with sPIF had higher medication costs compared with those with optimal PIF (cost ratio [CR]: 1.07, 95% CI [1.01, 1.14]). Multiple inhalation technique errors were associated with increased HCRU. Specifically, "insufficient inspiratory effort" with higher secondary healthcare costs (CR: 2.20, 95% CI [1.37, 3.54]) and higher total COPD-related costs (CR: 1.16, 95% CI 1.03-1.31). "no breath-hold following the inhalation manoeuvre (<6 s)" with higher medication costs (CR: 1.08, 95% CI [1.02, 1.15]) and total COPD-related costs (CR 1.17, 95% CI [1.07, 1.28]), and "not breathing out calmly after inhalation" with higher medication costs (CR: 1.19, 95% CI [1.04, 1.37]). Non-adherence was not significantly associated with HCRU. Conclusion: sPIF and inhalation technique errors were associated with higher COPD-related healthcare utilisation and costs in COPD patients on DPI maintenance therapy

Factors associated with health status and exacerbations in COPD maintenance therapy with dry powder inhalers

Funding Information: J.K. reports grants, personal fees and non-financial support from AstraZeneca, GSK and Boehringer Ingelheim; grants and personal fees from Chiesi Pharmaceuticals and TEVA; grants from Mundipharma; personal fees from MSD and COVIS Pharma; and also holds 72.5% of shares in the General Practitioners Research Institute. H.W. has received grants from Boehringer Ingelheim, which is the financial and scientific partner of GPRI for the submitted study, and from AstraZeneca, Novartis and Chiesi for scientific projects in the area of COPD/asthma. S.B.-A. has received grants from TEVA, and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Sanofi and Mylan. J.C.d.S. reports or personal fees from AstraZeneca, Bial, Boehringer Ingelheim, GSK, Medinfar, Mundipharma and Sanofi. B.C. received honorarium from GSK and Sanofi. J.v.C., L.D., I.v.G.-P., I.v.d.H., Y.J., M.K., B.M., K.S., N.S., M.H., B.M. and M.T.L. were employed by General Practitioners Research Institute (GPRI) at the time of the study. In the past three years (2019–2021), GPRI conducted investigator- and sponsor-initiated research funded by non-commercial organizations, academic institutes, and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, and Teva). R.D. has received grants and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Chiesi, Focus Care, and Glenmark. R.G. has received personal fees from AstraZeneca, GSK and Chiesi. E.D. holds 27.5% of shares in the General Practitioners Research Institute. M.G.P. receives grants from AstraZeneca, GSK and Boehringer Ingelheim. A.G. and A.d.l.H. are employees of Boehringer Ingelheim. F.L. received grants and personal fees from GSK, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini International, Novartis, Orion, and Trudell International, outside the submitted work. T.M. is an Assoicate Editor at npj Primary Care Respiratory Medicine. J.M. received grants from Boehringer Ingelheim, during the conduct of the study; and grants from AstraZeneca, Chiesi, Novartis, and GSK, outside the submitted work. D.P. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Theravance and Zentiva (Sanofi Generics); grants from the British Lung Foundation, Respiratory Effectiveness Group, UK National Health Service, and AKL Research and Development Ltd; personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, and WebMD Global LLC; non-financial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. M.R.-R. receives grants and personal fees from AstraZeneca and GSK; and personal fees from Boehringer Ingelheim, Chiesi, Menarini, Mundipharma, Novartis, Pfizer, TEVA and BIAL. I.T. reports grants and personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Chiesi and Elpen. O.U. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Edmond Pharma, Chiesi and GSK; grants from Edmond Pharma; and personal fees from Napp, Mundipharma, Sandoz, Takeda, Cipla, COVIS, Novartis, Mereobiopharma, Orion, and Menarini. S.B.-A. and T.M. are Associate Editors at npj Primary Care Respiratory Medicine, and I.T. is Editor in Chief. These authors were not involved in the journal’s review of, or decisions related to, this manuscript.Peer reviewedPublisher PD

Latent provisions for building information modeling (BIM) contracts: a social network analysis approach

The effective adoption and use of Building Information Modeling (BIM) require appropriate contract design to fairly allocate the contracting parties’ rights and responsibilities. Several standards for BIM protocols and contracts have been developed for the industry. However, the awareness and the use of these are rather limited, leading to unclear provisions in BIM contracts. Therefore, the research aims to identify the influential legal aspects that serve as the latent contract provisions in BIM contracts. A questionnaire survey was conducted to survey experts and active BIM users in construction projects. The data were analyzed using social network analysis (SNA) by assuming interdependent relationships among various the legal aspects in BIM contacts. The key legal aspects associated with BIM contracts pertain to the roles and responsibilities of the project participants. The results also reveal that data security is the center of all latent legal aspects in the contracts. The study provides significant new insights into clarifying the required contract provisions in BIM contracts

Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis

BACKGROUND: There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. OBJECTIVE: To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. METHODS: Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane-Armitage trend test implemented in PLINK. RESULTS: One SNP in the LPP gene, rs1464510, showed significant association with JIA (p(trend)=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (p(trend)=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p(trend)=0.005, OR=1.88, 95% CI 1.2 to 2.94). CONCLUSIONS: Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

&lt;p&gt;Objectives: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.&lt;/p&gt; &lt;p&gt;Methods: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.&lt;/p&gt; &lt;p&gt;Results: Thirteen SNP showed significant association (p&#60;0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.&lt;/p&gt; &lt;p&gt;Conclusions: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.&lt;/p&gt

Comparison of Storage Conditions for Human Vaginal Microbiome Studies

BACKGROUND: The effect of storage conditions on the microbiome and metabolite composition of human biological samples has not been thoroughly investigated as a potential source of bias. We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and (1)H-NMR analyses. METHODOLOGY/PRINCIPAL FINDINGS: Eight women were enrolled and four mid-vaginal swabs were collected by a physician from each woman. The samples were either processed immediately, stored at -80°C for 4 weeks or at -20°C for 1 week followed by transfer to -80°C for another 4 weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial community composition and metabolites between samples stored under different conditions. The results showed that there were no significant differences between samples processed immediately after collection or stored for varying durations. (1)H-NMR analysis of the small molecule metabolites in vaginal secretions indicated that high levels of lactic acid were associated with Lactobacillus-dominated communities. Relative abundance of lactic acid did not appear to correlate with relative abundance of individual Lactobacillus sp. in this limited sample, although lower levels of lactic acid were observed when L. gasseri was dominant, indicating differences in metabolic output of seemingly similar communities. CONCLUSIONS/SIGNIFICANCE: These findings benefit large-scale, field-based microbiome and metabolomic studies of the vaginal microbiota