Perioperative SARS-CoV-2 infections increase mortality, pulmonary complications, and thromboembolic events : a Dutch, multicenter, matched-cohort clinical study

Background: A direct comparison of severe acute respiratory syndrome coronavirus 2 positive patients with a severe acute respiratory syndrome coronavirus 2 negative control group undergoing an operative intervention during the current pandemic is lacking, and a reliable estimate of the assumed difference in morbidity and mortality between both patient categories remains unknown. Methods: We included all consecutive patients with a confirmed pre- or postoperative severe acute respiratory syndrome coronavirus 2 positive status (operated in 27 hospitals) and negative control patients (operated in 4 hospitals) undergoing emergency or elective operations. A propensity score-matched comparison of clinical outcomes was performed between severe acute respiratory syndrome coronavirus 2 positive and negative tested patients (control group). Primary outcome was overall 30-day mortality rate between both groups. Main secondary outcomes were overall, pulmonary, and thromboembolic complications. Results: In total, 161 severe acute respiratory syndrome coronavirus 2 positive and 342 control severe acute respiratory syndrome coronavirus 2 negative patients were included in this study. The 30-day overall postoperative mortality rate was greater in the severe acute respiratory syndrome coronavirus 2 positive cohort compared with the negative control group (16% vs 4% respectively; P = .007). After propensity score matching, the severe acute respiratory syndrome coronavirus 2 positive group consisted of 123 patients (median 70 years of age [interquartile range 59-77] and 55% male) were compared with 196 patients in the matched control group (median 69 years (interquartile range 58-75] and 53% male). The 30-day mortality rate and risk were greater in the severe acute respiratory syndrome coronavirus 2 positive group compared with the matched control group (12% vs 4%; P = .009 and odds ratio 3.4 [95% confidence interval 1.5-8.5]; P = .005, respectively). Overall, pulmonary and thromboembolic complications occurred more often in severe acute respiratory syndrome coronavirus 2 positive patients (P < .01). Conclusion: Patients diagnosed with perioperative severe acute respiratory syndrome coronavirus 2 have an increased risk of 30-day mortality, pulmonary complications, and thromboembolic events. These findings serve as an evidence-based argument to postpone elective surgery and selected emergency cases. (C) 2020 The Author(s). Published by Elsevier Inc

Intratympanic gentamicin treatment for Ménière's disease: A randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study

Background: Gentamicin is used as a therapeutic agent for Ménière's disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Ménière's disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation.Methods: We performed a randomized, double-blind, placebo-controlled study in adults with unilateral Ménière's disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years.Results: During follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group.Conclusion: No conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed.Trial registration: This trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37

The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Development and internal validation of prediction models for future hospital care utilization by patients with multimorbidity using electronic health record data

OBJECTIVE: To develop and internally validate prediction models for future hospital care utilization in patients with multiple chronic conditions. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in the Netherlands (542 beds) PARTICIPANTS: All adult patients (n = 18.180) who received care at the outpatient clinic in 2017 for two chronic diagnoses or more (including oncological diagnoses) and who returned for hospital care or outpatient clinical care in 2018. Development and validation using a stratified random split-sample (n = 12.120 for development, n = 6.060 for internal validation). OUTCOMES: ≥2 emergency department visits in 2018, ≥1 hospitalization in 2018 and ≥12 outpatient visits in 2018. STATISTICAL ANALYSIS: Multivariable logistic regression with forward selection. RESULTS: Evaluation of the models’ performance showed c-statistics of 0.70 (95% CI 0.69–0.72) for the hospitalization model, 0.72 (95% CI 0.70–0.74) for the ED visits model and 0.76 (95% 0.74–0.77) for the outpatient visits model. With regard to calibration, there was agreement between lower predicted and observed probability for all models, but the models overestimated the probability for patients with higher predicted probabilities. CONCLUSIONS: These models showed promising results for further development of prediction models for future healthcare utilization using data from local electronic health records. This could be the first step in developing automated alert systems in electronic health records for identifying patients with multimorbidity with higher risk for high healthcare utilization, who might benefit from a more integrated care approach

The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands

Background Low mixed or central venous saturation (S(c)vO(2)) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO(2) >= 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines. Methods In this prospective observational multi-center study, we determined central venous pressure (CVP), hematocrit, pH, lactate and ScvO(2) or SvO(2) in a heterogeneous group of critically ill patients early after admission to the intensive care units (ICUs) in three Dutch hospitals. Results Data of 340 acutely admitted critically ill patients were collected. The mean SvO(2) value was > 65% and the mean ScvO(2) value was > 70%. With mean CVP of 10.3 +/- 5.5 mmHg, lactate plasma levels of 3.6 +/- 3.6 and acute physiology, age and chronic health evaluation (APACHE II) scores of 21.5 +/- 8.3, the in-hospital mortality of the total heterogeneous population was 32.0%. A subgroup of septic patients (n = 125) showed a CVP of 9.8 +/- 5.4 mmHg, mean ScvO(2) values of 74.0 +/- 10.2%, where only 1% in this subgroup revealed a ScvO(2) value <50%, and lactate plasma levels of 2.7 +/- 2.2 mmol/l with APACHE II scores 20.9 +/- 7.3. Hospital mortality of this subgroup was 26%. Conclusion The incidence of low ScvO(2) values for acutely admitted critically ill patients is low in Dutch ICUs. This is especially true for patients with sepsis/septic shock