Home-based initiatives for acute management of COVID-19 patients needing oxygen: differences across The Netherlands.

OBJECTIVE: During the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview focused on differences and similarities of initiatives of acute home-based management in the Netherlands. METHODS: Initiatives were eligible for evaluation if (i) COVID-19 patients received oxygen treatment at home; (ii) patients received structured remote monitoring; (iii) it was not an 'early hospital discharge' program; (iv) at least one patient was included. Protocols were screened, and additional information was obtained from involved physicians. Design choices were categorised into: eligible patient group, organization medical care, remote monitoring, nursing care, and devices used. RESULTS: Nine initiatives were screened for eligibility; five were included. Three initiatives included low-risk patients and two were designed specifically for frail patients. Emergency department (ED) visit for an initial diagnostic work-up and evaluation was mandatory in three initiatives before starting home management. Medical responsibility was either assigned to the general practitioner or hospital specialist, most often pulmonologist or internist. Pulse-oximetry was used in all initiatives, with additional monitoring of heart rate and respiratory rate in three initiatives. Remote monitoring staff's qualification and authority varied, and organization and logistics were covered by persons with various backgrounds. All initiatives offered remote monitoring via an application, two also offered a paper diary option. CONCLUSIONS: We observed differences in the organization of interprofessional collaboration for acute home management of hypoxemic COVID-19 patients. All initiatives used pulse-oximetry and an app for remote monitoring. Our overview may be of help to healthcare providers and organizations to set up and implement similar acute home management initiatives for critical episodes of COVID-19 (or other acute disorders) that would otherwise require hospital care.

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study.

BACKGROUND: The preoperative period can be used to enhance a patient's functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme. METHODS: The multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes. DISCUSSION: Since the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients. TRIAL REGISTRATION: The current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080 . Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Starting Home Telemonitoring and Oxygen Therapy Directly after Emergency Department Assessment Appears to Be Safe in COVID-19 Patients.

BACKGROUND: Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many advantages, we evaluated these parameters in this study. METHODS: All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups. RESULTS: 278 patients were included (n = 65 ED group, n = 213 admission group). ED group: 23.8% (n = 15) was reassessed, 15.9% (n = 10) was admitted and 7.7% (n = 5) ICU admitted. Admission group: 15.8% (n = 37) was reassessed, 6.5% (n = 14) was readmitted and 2.4% (n = 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7-13) days; the total duration of home telemonitoring was 14 (IQR 9-18) days. Admission group: duration of oxygen therapy was 10 (IQR 6-16) days; total duration of home telemonitoring was 14 (IQR 10-20) days. CONCLUSION: it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.

Influence of esomeprazole on the bioavailability of afatinib: A pharmacokinetic cross-over study in patients with non-small cell lung cancer.

Afatinib is an oral small-molecule kinase inhibitor (SMKI) approved for treatment of metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) driver mutation. Although oral administration is convenient, most SMKIs experience pH-dependent solubility. A drug-drug interaction between afatinib and proton-pump inhibitors (PPIs) has, however, never been studied in humans. Hence, we performed a randomized, three-period cross-over study. Afatinib (30 mg or 40 mg) was administered without PPI (period A), concomitantly with esomeprazole (period B) and three hours after esomeprazole intake (period C). Primary objective was the area under the curve (AUC0-24 h) comparing period A to period B and period A to period C. Secondary objectives were other pharmacokinetic parameters and toxicity. Linear mixed effect modelling was performed for differences in AUC0-24 h and Cmax between periods A and B and periods A and C. In 18 evaluable NSCLC patients, concomitant use of 40 mg esomeprazole decreased the steady-state afatinib AUC0-24 h with 10.2% (95% CI -29.2 to +14.0%; p = 0.564) compared to afatinib administration without PPI. Esomeprazole intake three hours prior to afatinib did not significantly influence afatinib AUC0-24 h (-0.6%; 95% CI -14.9 to +16.1%; p = 1.0). No differences in toxicity were observed. To conclude, esomeprazole did not change the exposure to afatinib in patients with NSCLC. Since there is no clinically relevant drug-drug interaction, esomeprazole can safely be co-administered with afatinib. This is important for clinical practice, because other EGFR-SMKIs (e.g. erlotinib and gefitinib) do experience clinically relevant drug-drug interactions with acid-suppressive agents.

Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19-A Prospective Cohort Study.

Background Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients. Methods Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies. Results Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and "CTPA only" in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04-7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3-16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6-7.0). Conclusion Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.

Wide Variation in Perioperative Care in Anatomical Lung Resections in the Netherlands: A National Survey.

This study aimed to describe perioperative care after anatomical lung resection in the Netherlands, before publication of Enhanced Recovery After Surgery/European Society of Thoracic Surgeons (ERAS/ESTS) guidelines in 2019. An online survey was sent to all 43 Dutch lung surgical centers in December 2017, addressing topics in the 4 phases of perioperative care (preoperative, admission, perioperative, postoperative). Respondents were requested to report care that would be delivered to a standardized patient without perioperative complications. To compare current care with ERAS/ESTS guidelines, we assigned an ERAS/ESTS score per hospital, weighted for evidence level per recommendation. Higher scores indicate higher application of recommendations. Response rate of centers was 100%, median response rate per question was 98% (interquartile range 94-100). Some perioperative recommendations are commonly applied (>85%), such as minimally invasive surgery and regional anesthesia; others, such as admission carbohydrate drinks, are not (<35%). Wide variation was observed regarding patient counselling, pre- and postoperative admission logistics, anemia correction, fluid management, pain management, and chest drain management. Median 62% (interquartile range 53%-72%) of the maximum ERAS/ESTS score was achieved. Large variation in ERAS/ESTS score between hospitals were found in all phases (preoperative: 6.0 [6.5-10.5] points, admission: 5.0 [1.0-6.0] points, perioperative: 21.5.0 [16.0-22.5] points, postoperative: 8.0 [5.0-8.5] points). Large variation exists in perioperative care after anatomical lung resection in the Netherlands. Given previously published data linking variation in perioperative care to variation in outcomes, standardization of perioperative care in lung surgery, preferably based on the ERAS/ESTS guidelines, may be warranted but requires further study.

Variation in length of stay after minimally invasive lung resection: a reflection of perioperative care routines?

OBJECTIVES: Good perioperative care is aimed at rapid recovery, without complications or readmissions. Length of stay (LOS) is influenced not only by perioperative care routines but also by patient factors, tumour factors, treatment characteristics and complications. The present study examines variation in LOS between hospitals after minimally invasive lung resections for both complicated and uncomplicated patients to assess whether LOS is a hospital characteristic influenced by local perioperative routines or other factors. METHODS: Dutch Lung Cancer Audit (surgery) data were used. Median LOS was calculated on hospital level, stratified by the severity of complications. Lowest quartile (short) LOS per hospital, corrected for case-mix factors by multivariable logistic regression, was presented in funnel plots. We correlated short LOS in complicated versus uncomplicated patients to assess whether short LOS clustered in the same hospitals regardless of complications. RESULTS: Data from 6055 patients in 42 hospitals were included. Median LOS in uncomplicated patients varied from 3 to 8 days between hospitals and increased most markedly for patients with major complications. Considerable between-hospital variation persisted after case-mix correction, but more in uncomplicated than complicated patients. Short LOS in uncomplicated and complicated patients were significantly correlated (r = 0.53, P < 0.001). CONCLUSIONS: LOS after minimally invasive anatomical lung resections varied between hospitals particularly in uncomplicated patients. The significant correlation between short LOS in uncomplicated and complicated patients suggests that LOS is a hospital characteristic potentially influenced by local processes. Standardizing and optimizing perioperative care could help limit practice variation with improved LOS and complication rates.

Variation in length of hospital stay after lung cancer surgery in the Netherlands.

OBJECTIVES: Length of stay (LOS) in the hospital after lung cancer surgery is influenced by patient characteristics, tumour characteristics, surgical technique and perioperative care. Our objective was to determine whether there were variation in LOS between hospitals that could not be accounted for by these known parameters. Residual variation in LOS would suggest important differences in perioperative care protocols and discharge criteria. METHODS: This study analysed data from the Netherlands National Cancer Registry (NNCR) on 10 195 anatomical lung resections for primary lung cancer from 2010 to 2015. Multivariable analysis was performed for multiple factors, using hierarchical linear regression analysis of the mean LOS. Information on comorbidity and socio-economic status was not available. Association between LOS and postoperative mortality was evaluated in multivariable logistic regression. RESULTS: The median LOS was 7 days (interquartile range 5-10 days), and the mean LOS was 8.3 days. LOS was negatively affected by larger resections, open surgery and advancing age. Histology and tumour stage had little influence. Overall, 30-day and 90-day mortality were 2.1% and 3.8%, respectively; 1.7% and 3.3% (not significant) in the group of hospitals with shorter LOS. After case-mix correction, residual between-hospital variation in the mean LOS was observed, ranging from 1.5 days shorter to almost 2.5 days longer. CONCLUSIONS: A clinically relevant between-hospital variation in LOS after lung cancer surgery is observed in the Netherlands. Although residual confounding by comorbidity or socio-economic status cannot be excluded, this variation is deemed to be largely due to differences in perioperative care protocols. Evaluation of best practices can help to improve perioperative care for lung surgery patients and optimize LOS.

Malignant pleural mesothelioma: when is radiation therapy indicated?

Malignant pleural mesothelioma is an aggressive tumor of serosal surfaces resistant to many current treatment options. This article will provide a comprehensive discussion of the latest developments in the treatment of malignant pleural mesothelioma, with a focus on radiation therapy. We will discuss the role of radiotherapy as a prophylactic, palliative and potentially curative treatment of malignant pleural mesothelioma. An update will be provided of the latest clinical trials including new treatment.

Investigational approaches for mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000-2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

European guidelines for the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is nearly invariably lethal tumor of the pleura. Significant therapeutic nihilism exists among health professionals. Recent progress has reshaped the clinical landscape in the treatment of MPM. Two European guidelines have been published, one from the task force of the European Respiratory Society and the European Society of Thoracic Surgery, and the other from the European Society of Medical Oncology. With these guidelines and recommendations as a guidepost, this review discusses the major changes and their impact on the management of MPM.