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  1. Article: Dynamic fair balancing of COVID-19 patients over hospitals based on forecasts of bed occupancy.

    Dijkstra, Sander / Baas, Stef / Braaksma, Aleida / Boucherie, Richard J

    Omega

    2022  Volume 116, Page(s) 102801

    Abstract: This paper introduces mathematical models that support dynamic fair balancing of COVID-19 patients over hospitals in a region and across regions. Patient flow is captured in an infinite server queueing network. The dynamic fair balancing model within a ... ...

    Abstract This paper introduces mathematical models that support dynamic fair balancing of COVID-19 patients over hospitals in a region and across regions. Patient flow is captured in an infinite server queueing network. The dynamic fair balancing model within a region is a load balancing model incorporating a forecast of the bed occupancy, while across regions, it is a stochastic program taking into account scenarios of the future bed surpluses or shortages. Our dynamic fair balancing models yield decision rules for patient allocation to hospitals within the region and reallocation across regions based on safety levels and forecast bed surplus or bed shortage for each hospital or region. Input for the model is an accurate real-time forecast of the number of COVID-19 patients hospitalised in the ward and the Intensive Care Unit (ICU) of the hospitals based on the predicted inflow of patients, their Length of Stay and patient transfer probabilities among ward and ICU. The required data is obtained from the hospitals' data warehouses and regional infection data as recorded in the Netherlands. The algorithm is evaluated in Dutch regions for allocation of COVID-19 patients to hospitals within the region and reallocation across regions using data from the second COVID-19 peak.
    Language English
    Publishing date 2022-11-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 1491111-5
    ISSN 1873-5274 ; 0305-0483
    ISSN (online) 1873-5274
    ISSN 0305-0483
    DOI 10.1016/j.omega.2022.102801
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  2. Article ; Online: Challenges of denosumab in giant cell tumor of bone, and other giant cell-rich tumors of bone.

    Lipplaa, Astrid / Dijkstra, Sander / Gelderblom, Hans

    Current opinion in oncology

    2019  Volume 31, Issue 4, Page(s) 329–335

    Abstract: Purpose of review: Giant cell tumor of bone (GCTB) is an uncommon benign primary bone tumor, consisting of receptor activator of nuclear factor kappa-B (RANK) expressing reactive osteoclast-like giant cells and neoplastic spindle-shaped cells. Denosumab ...

    Abstract Purpose of review: Giant cell tumor of bone (GCTB) is an uncommon benign primary bone tumor, consisting of receptor activator of nuclear factor kappa-B (RANK) expressing reactive osteoclast-like giant cells and neoplastic spindle-shaped cells. Denosumab was approved by FDA in 2013 and by EMA in 2014 to treat adults and skeletally mature adolescents with unresectable GCTB or when resection is likely to result in severe morbidity. However, there is much discussion regarding the optimal applied treatment strategy.
    Recent findings: Neoadjuvant treatment of GCTB with denosumab can effectively downstage tumors to facilitate less morbid surgery or completely avoid the need for resection, but there is concern about local recurrence postsurgery. Definitive treatment of unresectable GTCB improves symptoms and halts tumor progression. The optimal treatment duration is unclear and long-term treatment is associated with adverse events like osteonecrosis of the jaw (ONJ) and atypical femoral fractures. Denosumab maintenance dose interval is currently being investigated.
    Summary: For the related but heterogenous group of giant cell rich tumors of bone, like aneurysmal bone cysts (ABC) and central giant cell granuloma (CGCG), denosumab is a new treatment modality under investigation. Given the effectiveness in GCTB, this could be a promising treatment option for selected patients with advanced disease.
    MeSH term(s) Bone Density Conservation Agents/administration & dosage ; Bone Neoplasms/drug therapy ; Bone Neoplasms/pathology ; Bone Neoplasms/surgery ; Chemotherapy, Adjuvant ; Denosumab/administration & dosage ; Giant Cell Tumor of Bone/drug therapy ; Giant Cell Tumor of Bone/pathology ; Giant Cell Tumor of Bone/surgery ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Randomized Controlled Trials as Topic
    Chemical Substances Bone Density Conservation Agents ; Denosumab (4EQZ6YO2HI)
    Language English
    Publishing date 2019-03-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1049384-0
    ISSN 1531-703X ; 1040-8746
    ISSN (online) 1531-703X
    ISSN 1040-8746
    DOI 10.1097/CCO.0000000000000529
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  3. Article ; Online: Limited waiting areas in outpatient clinics: an intervention to incorporate the effect of bridging times in blueprint schedules.

    Dijkstra, Sander / Otten, Maarten / Leeftink, Gréanne / Kamphorst, Bas / Olde Meierink, Angelique / Heinen, Anouk / Bijlsma, Rhodé / Boucherie, Richard J

    BMJ open quality

    2022  Volume 11, Issue 2

    Abstract: Background: Distancing measures enforced by the COVID-19 pandemic impose a restriction on the number of patients simultaneously present in hospital waiting areas.: Objective: Evaluate waiting area occupancy of an intervention that designs clinic ... ...

    Abstract Background: Distancing measures enforced by the COVID-19 pandemic impose a restriction on the number of patients simultaneously present in hospital waiting areas.
    Objective: Evaluate waiting area occupancy of an intervention that designs clinic blueprint schedules, in which all appointments of the pre-COVID-19 case mix are scheduled either digitally or in person under COVID-19 distancing measures, whereby the number of in-person appointments is maximised.
    Methods: Preintervention analysis and prospective assessment of intervention outcomes were used to evaluate the outcomes on waiting area occupancy and number of in-person consultations (postintervention only) using descriptive statistics, for two settings in the Rheumatology Clinic of Sint Maartenskliniek (SMK) and Medical Oncology & Haematology Outpatient Clinic of University Medical Center Utrecht (UMCU). Retrospective data from October 2019 to February 2020 were used to evaluate the pre-COVID-19 blueprint schedules. An iterative optimisation and simulation approach was followed, based on integer linear programming and Monte Carlo simulation, which iteratively optimised and evaluated blueprint schedules until the 95% CI of the number of patients in the waiting area did not exceed available capacity.
    Results: Under pre-COVID-19 blueprint schedules, waiting areas would be overcrowded by up to 22 (SMK) and 11 (UMCU) patients, given the COVID-19 distancing measures. The postintervention blueprint scheduled all appointments without overcrowding the waiting areas, of which 88% and 87% were in person and 12% and 13% were digitally (SMK and UMCU, respectively).
    Conclusions: The intervention was effective in two case studies with different waiting area characteristics and a varying number of interdependent patient trajectory stages. The intervention is generically applicable to a wide range of healthcare services that schedule a (series of) appointment(s) for their patients. Care providers can use the intervention to evaluate overcrowding of waiting area(s) and design optimal blueprint schedules to continue a maximum number of in-person appointments under pandemic distancing measures.
    MeSH term(s) Ambulatory Care Facilities ; COVID-19/prevention & control ; Humans ; Pandemics/prevention & control ; Prospective Studies ; Retrospective Studies
    Language English
    Publishing date 2022-06-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-6641
    ISSN (online) 2399-6641
    DOI 10.1136/bmjoq-2021-001703
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  4. Article ; Online: Current concepts in the treatment of giant cell tumour of bone.

    van der Heijden, Lizz / Dijkstra, Sander / van de Sande, Michiel / Gelderblom, Hans

    Current opinion in oncology

    2020  Volume 32, Issue 4, Page(s) 332–338

    Abstract: Purpose of review: Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor κ-B-ligand ... ...

    Abstract Purpose of review: Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor κ-B-ligand inhibitor, was introduced as systemic targeted therapy for advanced or inoperable and metastatic GCTB. Also, the bisphosphonate zoledronic acid has activity in GCTB by directly targeting the neoplastic stromal cells.
    Recent findings: In a small RCT, bisphosphonates were successful in controlling tumour growth and a higher apoptotic index of tumour cells was seen after zoledronic acid versus controls. Although bisphosphonate-loaded bone cement has not been studied to a large extent, it does not seem harmful and may constitute a logical local adjuvant. From the largest clinical trial to date, the risk-to-benefit ratio for denosumab in patients with advanced GCTB remains favourable, also in facilitating less morbid surgery. Concerns have arisen that recurrence rates would be higher than after conventional treatment, ranging from 20 to 100% in a systematic review, although this may be because of bias. H3F3A (G34W) driver mutations are helpful in the differentiation between GCTB and other giant cell-containing malignancies. H3.3-G34W proved sufficient to drive tumourigenesis. The cumulative incidence of malignancy in GCTB is estimated at 4%, of which primary malignancy 1.6% and secondary malignancy 2.4%, the latter mainly after radiation. To date, a potential causal relationship between denosumab and pulmonary metastases has not been confirmed; if they do not behave indolently, it would be advised to reassess diagnosis and consider malignancy.
    Summary: Denosumab remains a highly effective treatment option for patients with advanced GCTB. A short duration of 2-4 months neoadjuvant denosumab is advised to facilitate less morbid surgery and prevent incomplete curettage by macroscopic tumour alterations. Reduced dose intensity is being studied to reduce long term side-effects. Further research on bisphosphonates and other targets including H3.3-G34W remains warranted.
    MeSH term(s) Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/drug therapy ; Bone Neoplasms/pathology ; Bone Neoplasms/surgery ; Denosumab/therapeutic use ; Giant Cell Tumor of Bone/drug therapy ; Giant Cell Tumor of Bone/pathology ; Giant Cell Tumor of Bone/surgery ; Humans ; Neoadjuvant Therapy ; Randomized Controlled Trials as Topic ; Zoledronic Acid/therapeutic use
    Chemical Substances Bone Density Conservation Agents ; Denosumab (4EQZ6YO2HI) ; Zoledronic Acid (6XC1PAD3KF)
    Language English
    Publishing date 2020-06-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1049384-0
    ISSN 1531-703X ; 1040-8746
    ISSN (online) 1531-703X
    ISSN 1040-8746
    DOI 10.1097/CCO.0000000000000645
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  5. Article ; Online: Real-time forecasting of COVID-19 bed occupancy in wards and Intensive Care Units.

    Baas, Stef / Dijkstra, Sander / Braaksma, Aleida / van Rooij, Plom / Snijders, Fieke J / Tiemessen, Lars / Boucherie, Richard J

    Health care management science

    2021  Volume 24, Issue 2, Page(s) 402–419

    Abstract: This paper presents a mathematical model that provides a real-time forecast of the number of COVID-19 patients admitted to the ward and the Intensive Care Unit (ICU) of a hospital based on the predicted inflow of patients, their Length of Stay (LoS) in ... ...

    Abstract This paper presents a mathematical model that provides a real-time forecast of the number of COVID-19 patients admitted to the ward and the Intensive Care Unit (ICU) of a hospital based on the predicted inflow of patients, their Length of Stay (LoS) in both the ward and the ICU as well as transfer of patients between the ward and the ICU. The data required for this forecast is obtained directly from the hospital's data warehouse. The resulting algorithm is tested on data from the first COVID-19 peak in the Netherlands, showing that the forecast is very accurate. The forecast may be visualised in real-time in the hospital's control centre and is used in several Dutch hospitals during the second COVID-19 peak.
    MeSH term(s) Bed Occupancy/trends ; COVID-19 ; Forecasting ; Hospitals ; Humans ; Intensive Care Units ; Kaplan-Meier Estimate ; Models, Statistical ; Netherlands ; SARS-CoV-2
    Language English
    Publishing date 2021-03-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1469148-6
    ISSN 1572-9389 ; 1386-9620
    ISSN (online) 1572-9389
    ISSN 1386-9620
    DOI 10.1007/s10729-021-09553-5
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  6. Article: Efficacy of pazopanib and sunitinib in advanced axial chordoma: a single reference centre case series.

    Lipplaa, Astrid / Dijkstra, Sander / Gelderblom, Hans

    Clinical sarcoma research

    2016  Volume 6, Page(s) 19

    Abstract: Background: Chordomas are rare malignant tumours of the axial skeleton and skull base supposed to arise from cellular remnants of the notochord. These tumours have the potential to metastasize (30-40 %), usually in the later course of the disease. ... ...

    Abstract Background: Chordomas are rare malignant tumours of the axial skeleton and skull base supposed to arise from cellular remnants of the notochord. These tumours have the potential to metastasize (30-40 %), usually in the later course of the disease. However, the greatest morbidity is usually a result of loco-regional recurrence with infiltration and destruction of surrounding bone and soft tissue. Patients with unresectable or metastatic chordoma are faced with a poor prognosis since cytotoxic chemotherapy or other systemic therapies have not proven their efficacy yet. However, several molecularly targeted drugs have been proposed as potentially beneficial, including tyrosine kinase inhibitors (TKIs) directed at vascular endothelial growth factor receptor (VEGFR), like pazopanib and sunitinib.
    Case presentation: Five patients with unresectable or metastatic chordoma were treated with VEGFR inhibitors pazopanib or sunitinib in the Leiden University Medical Centre (LUMC) between 2008 and 2015. Two out of four patients treated with pazopanib derived clinical benefit and disease remained stable for respectively 14 and 15 months. The one patient treated with sunitinib achieved a partial response according to RECIST 1.1 which lasted for a total of 27 months. No serious adverse events were observed.
    Conclusion: These results on the use of pazopanib and sunitinib in chordoma are promising, with an objective response on sunitinib and a median progression free interval of 8.5 months (range 3-15 months), comparable to that of imatinib, in the pazopanib subgroup. However further research is needed to assess the definite role of VEGFR inhibitors in chordoma.
    Language English
    Publishing date 2016-11-01
    Publishing country England
    Document type Case Reports
    ZDB-ID 2623217-0
    ISSN 2045-3329
    ISSN 2045-3329
    DOI 10.1186/s13569-016-0059-x
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  7. Article ; Online: Ribbing disease: a systematic review.

    Pijls, Bart G / Steentjes, Koen / Schoones, Jan W / Dijkstra, Sander Pd

    Acta radiologica (Stockholm, Sweden : 1987)

    2017  Volume 59, Issue 4, Page(s) 448–453

    Abstract: Background Ribbing disease, or multiple diaphyseal sclerosis, is a rare benign bone dysplasia. Purpose To systematically review the literature to determine the clinical and radiological presentation of patients with Ribbing disease as well as the effects ...

    Abstract Background Ribbing disease, or multiple diaphyseal sclerosis, is a rare benign bone dysplasia. Purpose To systematically review the literature to determine the clinical and radiological presentation of patients with Ribbing disease as well as the effects of attempted treatments. Material and Methods We considered individual patient data of patients diagnosed with Ribbing disease derived from patient reports and patient series. All stages of the review were performed by two reviewers independently. Standard descriptive statistics were used for quantitative analyses and mixed model analyses were used when appropriate Results The literature search yielded 420 unique hits of which 23 studies were included, covering a total of 40 patients of whom 29 had bilateral involvement. The mean age at diagnosis was 35 years and the mean time between diagnosis and onset of symptoms, mostly pain, was five years (range = 1-16 years). The tibial diaphysis was the most commonly involved bone in 35 of 36 patients. Non-surgical treatment consisted of non-steroidal anti-inflammatory drugs (NSAIDs), prednisone, and bisphophonates with mixed results. Surgical treatment consisted of intramedullary reaming and fenestration and was very effective to reduce pain. Conclusion The clinical presentation and imaging findings of patients with Ribbing disease are becoming more apparent. However, there is paucity of evidence on the natural disease progression and effectiveness of treatment modalities.
    MeSH term(s) Adult ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Camurati-Engelmann Syndrome/diagnostic imaging ; Camurati-Engelmann Syndrome/therapy ; Female ; Glucocorticoids/therapeutic use ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Osteoma, Osteoid/diagnostic imaging ; Osteoma, Osteoid/therapy ; Prednisone/therapeutic use ; Tibia/diagnostic imaging ; Tibia/surgery ; Tomography, X-Ray Computed/methods ; X-Rays
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Glucocorticoids ; Prednisone (VB0R961HZT)
    Language English
    Publishing date 2017-07-10
    Publishing country England
    Document type Journal Article ; Systematic Review
    ZDB-ID 105-3
    ISSN 1600-0455 ; 0284-1851 ; 0349-652X
    ISSN (online) 1600-0455
    ISSN 0284-1851 ; 0349-652X
    DOI 10.1177/0284185117719575
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  8. Article ; Online: Adjuvant Zoledronic Acid in High-Risk Giant Cell Tumor of Bone: A Multicenter Randomized Phase II Trial.

    Lipplaa, Astrid / Kroep, Judith R / van der Heijden, Lizz / Jutte, Paul C / Hogendoorn, Pancras C W / Dijkstra, Sander / Gelderblom, Hans

    The oncologist

    2019  Volume 24, Issue 7, Page(s) 889–e421

    Abstract: Lessons learned: Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of giant cell tumor of bone (GCTB) in this study. The efficacy could not be determined because of the small sample size.GCTB recurrences, even in the denosumab ...

    Abstract Lessons learned: Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of giant cell tumor of bone (GCTB) in this study. The efficacy could not be determined because of the small sample size.GCTB recurrences, even in the denosumab era, are still an issue; therefore, a randomized study exploring the efficacy of zoledronic acid in the adjuvant setting in GCTB is still valid.
    Background: Bisphosphonates are assumed to inhibit giant cell tumor of bone (GCTB)-associated osteoclast activity and have an apoptotic effect on the neoplastic mononuclear cell population. The primary objective of this study was to determine the 2-year recurrence rate of high-risk GCTB after adjuvant zoledronic acid versus standard care.
    Methods: In this multicenter randomized open-label phase II trial, patients with high-risk GCTB were included (December 2008 to October 2013). Recruitment was stopped because of low accrual after the introduction of denosumab. In the intervention group, patients received adjuvant zoledronic acid (4 mg) intravenously at 1, 2, 3, 6, 9, and 12 months after surgery.
    Results: Fourteen patients were included (intervention
    Conclusion: Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of GCTB in this study. The efficacy could not be determined because of the small sample size. Because recurrences, even in the denosumab era, are still an issue, a randomized study exploring the efficacy of zoledronic acid in the adjuvant setting in GCTB is still valid.
    MeSH term(s) Adult ; Aged ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/drug therapy ; Bone Neoplasms/pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Giant Cell Tumor of Bone/drug therapy ; Giant Cell Tumor of Bone/pathology ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm Recurrence, Local/epidemiology ; Netherlands/epidemiology ; Prognosis ; Risk Factors ; Survival Rate ; Young Adult ; Zoledronic Acid/therapeutic use
    Chemical Substances Bone Density Conservation Agents ; Zoledronic Acid (6XC1PAD3KF)
    Language English
    Publishing date 2019-04-30
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1634/theoncologist.2019-0280
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    Zs.MO 494: Show issues

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  9. Article ; Online: In response.

    Nieuwenhuijse, Marc J / Dijkstra, Sander P D

    Spine

    2013  Volume 38, Issue 26, Page(s) 2304

    MeSH term(s) Bone Cements/therapeutic use ; Female ; Fractures, Compression/therapy ; Humans ; Male ; Osteoporotic Fractures/therapy ; Pain/prevention & control ; Vertebroplasty/methods
    Chemical Substances Bone Cements
    Language English
    Publishing date 2013-12-15
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 752024-4
    ISSN 1528-1159 ; 0362-2436
    ISSN (online) 1528-1159
    ISSN 0362-2436
    DOI 10.1097/BRS.0000000000000057
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  10. Article ; Online: Hyperplasia of rib and vertebra, associated with infiltrating lipoma: a rare case of focal overgrowth.

    de Poorter, Jolanda J / Kroon, Herman M / Dijkstra, Sander P D S

    European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

    2014  Volume 24 Suppl 4, Page(s) S485–8

    Abstract: Purpose: Syndromes with focal overgrowth are rare and diagnosis is difficult because manifestations are highly variable and symptoms overlap between syndromes. Diagnosis depends on clinical history, physical examination, and radiologic and histologic ... ...

    Abstract Purpose: Syndromes with focal overgrowth are rare and diagnosis is difficult because manifestations are highly variable and symptoms overlap between syndromes. Diagnosis depends on clinical history, physical examination, and radiologic and histologic findings. This report describes a case of focal overgrowth of the left seventh rib and half of the adjacent thoracic vertebra, with overlying infiltrating lipoma.
    Methods: A 13-year-old boy presented with an asymptomatic chest wall mass caused by enlargement of the seventh rib and an overlying soft-tissue mass accompanied by enlargement of half of the seventh thoracic vertebra. MRI showed infiltration of lipomatous tissue in the muscles, but no interfascicular accumulation of adipose tissue in the thoracic spinal nerve.
    Results: A similar case was presented in 1985 but without MR imaging.
    Conclusion: We report on a second case of focal overgrowth of a rib and half of the adjacent vertebra, and overlying lipoma. In addition to the first case, we present MR images demonstrating infiltration of the adipose tissue.
    MeSH term(s) Adolescent ; Humans ; Hyperplasia/etiology ; Hyperplasia/pathology ; Lipoma/complications ; Lipoma/diagnosis ; Magnetic Resonance Imaging ; Male ; Ribs/pathology ; Soft Tissue Neoplasms/complications ; Soft Tissue Neoplasms/diagnosis ; Thoracic Vertebrae/pathology
    Language English
    Publishing date 2014-08-20
    Publishing country Germany
    Document type Case Reports ; Journal Article
    ZDB-ID 1115375-1
    ISSN 1432-0932 ; 0940-6719
    ISSN (online) 1432-0932
    ISSN 0940-6719
    DOI 10.1007/s00586-014-3506-5
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