Multicomponent Prehabilitation as a Novel Strategy for Preventing Delirium in Older Chronic Limb Threatening Ischemia Patients: A Study Protocol.

Objective: Chronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥65 years. Design: A prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program. Methods: Chronic limb threatening ischemia patients ≥65 years that require revascularization will participate in the program. This program focuses on optimizing the patient's overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group. Discussion: This study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient's preoperative mental and physical condition to prevent postoperative complications, including delirium. Trial: This protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.

Heart failure with preserved, mid-range, and reduced ejection fraction across health care settings: an observational study.

AIMS: This study aimed to assess the sex-specific distribution of heart failure (HF) with preserved, mid-range, and reduced ejection fraction across three health care settings. METHODS AND RESULTS: In this descriptive observational study, we retrieved the distribution of HF types [with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF)] for men and women between 65 and 79 years of age in three health care settings from a single country: (i) patients with screening-detected HF in the high-risk community (i.e. those with shortness of breath, frailty, diabetes mellitus, and chronic obstructive pulmonary disease) from four screening studies, (ii) patients with confirmed HF from primary care derived from a single observational study, and (iii) patients with confirmed HF from outpatient cardiology clinics participating in a registry. Among 1407 patients from the high-risk community, 288 had screen-detected HF (15% HFrEF, 12% HFmrEF, 74% HFpEF), and 51% of the screen-detected HF patients were women. In both women (82%) and men (65%), HFpEF was the most prevalent HF type. In the routine general practice population (30 practices, 70 000 individuals), among the 160 confirmed HF cases, 35% had HFrEF, 23% HFmrEF, and 43% HFpEF, and in total, 43% were women. In women, HFpEF was the most prevalent HF type (52%), while in men, this was HFrEF (41%). In outpatient cardiology clinics (n = 34), of the 4742 HF patients (66% HFrEF, 15% HFmrEF, 20% HFpEF), 36% were women. In both women (56%) and men (71%), HFrEF was the most prevalent HF type. CONCLUSIONS: Both HF types and sex distribution vary considerably in HF patients of 65-79 years of age among health care settings. From the high-risk community through to general practice to the cardiology outpatient setting, there is a shift in HF type from HFpEF to HFrEF and a decrease in the proportion of HF patients that are women.

[Adenotonsillectomy with or without intubation? Safety of the adenotonsillectomy without endotracheal tube in children]. / Wel of geen intubatie bij adenotonsillectomie volgens Sluder?Resultaten.

OBJECTIVE: To determine the safety of the non-intubated and intubated adenotonsillectomy by the Sluder method in children DESIGN: Retrospective database study METHOD: We compared the data of adenotonsillectomy by the Sluder method in children until thirteen years of two teaching hospitals from 2014 until 2017. In the Amphia Hospital the procedure was performed without endotracheal tube placement and without perioperative opioids, in the Haga Hospital the patients were intubated and received perioperative opioids. Primary outcome was reoperation for postoperative haemorrhage. Secondary outcomes included desaturation (saturation ≤ 90% > 1 min), severe hypoxemia (saturation ≤ 85% for ≥ 5 min), airway complications, bradycardia, total postoperative haemorrhages, use of rescue medication, hospital readmission and 30-day mortality. RESULTS: A total of 1370 patients were analysed: 1267 adenotonsillectomies and 103 tonsillectomies. Median operation time was 7 minutes in the non-intubated group versus 12 minutes in the intubated group. The primary outcome occurred in thirteen patients in the group without intubation (2.2%) and eleven times in the group with intubation (1.4%). There was one case of severe hypoxemia in the group without intubation. Desaturation occurred mostly in the group without intubation (26.4%) for a short time (median 0 min, interquartile range 0-1). Bradycardia was seen more in the group with intubation (4.1% vs 2.2%). CONCLUSION: The incidence of postoperative haemorrhage and severe airway complications after adenotonsillectomy by the Sluder method with and without endotracheal tube placement in both groups was comparable.

Effect of the COVID-19 pandemic during the first lockdown in the Netherlands on the number of trauma-related admissions, trauma severity and treatment: the results of a retrospective cohort study in a level 2 trauma centre.

OBJECTIVES: To determine the impact of the first lockdown in the Netherlands' measures during the COVID-19 pandemic on the number and type of trauma-related injuries presenting to the emergency department (ED). DESIGN: A single-centre retrospective cohort study. SETTING: A level 2 trauma centre in Breda, The Netherlands. PARTICIPANTS: All patients with trauma seen at the ED between 11 March and 10 May 2020 (the first Dutch lockdown period) were included in this study. Comparable groups were generated for 2019 and 2018. MAIN OUTCOME MEASURES: Primary outcomes were the total number of patients with trauma admitted to the ED and the trauma mechanism. Secondary outcomes were triage categories, time of ED visit, trauma severity (Injury Severity Score (ISS) >12), anatomical region of injury and treatment. RESULTS: A total of 4674 patients were included in this study. During the first months of the COVID-19 pandemic, there was a decrease of 32% in traumatic injuries at the ED (n=1182) compared with the previous years 2019 (n=1717) and 2018 (n=1775) (p<0.001). Sports-related injuries decreased most during the lockdown (n=164) compared with 2019 (n=386) and 2018 (n=367) (p<0.001). We observed more frequent injuries due to a fall from standing height (p<0.001) and work-related injuries (p<0.05). The mean age was significantly higher (mean 48 years vs 42 and 43 years). There was no difference in anatomical place of injury or ISS >12. The amount of patients admitted for emergency surgery was significantly higher (14.6% vs 9.4%; 8.6%, p<0.001). Seven patients (0.6%) tested positive for COVID-19. CONCLUSIONS: Measures taken in the COVID-19 outbreak result in a predictable decrease in the total number of patients with trauma, especially sports-related trauma. Although the trauma burden on the emergency room appears to be lower, more people have been admitted for trauma surgery, possibly due to increased throughput in the operating theatres.

Disease-free and overall survival after neoadjuvant chemotherapy in breast cancer: breast-conserving surgery compared to mastectomy in a large single-centre cohort study.

PURPOSE: The extended role of breast-conserving surgery (BCS) in the neoadjuvant setting may raise concerns on the oncologic safety of BCS compared to mastectomy. This study compared long-term outcomes after neoadjuvant chemotherapy (NAC) between patients treated with BCS and mastectomy. METHODS: All breast cancer patients treated with NAC from 2008 until 2017 at the Amphia Hospital (the Netherlands) were included. Disease-free and overall survival were compared between BCS and mastectomy with survival functions. Multivariable Cox proportional hazard regression was performed to determine prognostic variables for disease-free survival. RESULTS: 561 of 612 patients treated with NAC were eligible: 362 (64.5%) with BCS and 199 (35.5%) with mastectomy. Median follow-up was 6.8 years (0.9-11.9). Mastectomy patients had larger tumours and more frequently node-positive or lobular cancer. Unadjusted five-year disease-free survival was 90.9% for BCS versus 82.9% for mastectomy (p = .004). Unadjusted five-year overall survival was 95.3% and 85.9% (p < .001), respectively. In multivariable analysis, clinical T4 (cT4) (HR 3.336, 95% CI 1.214-9.165, p = .019) and triple negative disease (HR 5.946, 95% CI 2.703-13.081, p < .001) were negative predictors and pathologic complete response of the breast (HR 0.467, 95% CI 0.238-0.918, p = .027) and axilla (HR 0.332, 95% CI 0.193-0.572, p = .001) were positive predictors for disease-free survival. Mastectomy versus BCS was not a significant predictor for disease-free survival when adjusted for the former variables (unadjusted HR 2.13 (95%CI: 1.4-3.24), adjusted HR 1.31 (95%CI: 0.81-2.13)). In the BCS group, disease-free and overall survival did not differ significantly between cT1, cT2 or cT3 tumours. CONCLUSION: BCS does not impair disease-free and overall survival in patients treated with NAC. Tumour biology and treatment response are significant prognostic indicators.

Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers.

Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the "bio depression score"). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P < .001), in serum (P = .02) and in the combined serum plus urine result (P < .001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.

Ileus caused by obstructing colorectal cancer-impact on long-term survival.

PURPOSE: It is unclear whether obstructing colorectal cancer (CRC) has a worse prognosis than non-obstructing CRC. Of CRC patients, 10-28% present with symptoms of acute obstruction. Previous studies regarding obstruction have been primarily based on short-term outcomes, risk factors and treatment modalities. With this study, we want to determine the long-term survival of patients presenting with acute obstructive CRC. METHODS: This single-centre observational retrospective cohort study includes all CRC patients who underwent surgery between December 2004 and 2010. Patients were divided into two groups: ileus and no ileus. Survival analyses were performed for both groups. Additional survival analyses were performed in patients with and without synchronous metastases. The primary outcome was survival in months. RESULTS: A total of 1236 patients were included in the analyses. Ileus occurred in 178 patients (14.4%). The 5-year survival for patients with an ileus was 32% and without 60% (P < 0.01). In patients without synchronous metastases, survival with and without an ileus was 40.9 and 68.4%, respectively (P < 0.01). If ileus presentation was complicated by a colon blowout, 5-year survival decreased to 29%. No significant difference was found in patients with synchronous metastases. Survival at 5 years in this subgroup was 10 and 12% for patients with and without an ileus, respectively (P = 0.705). CONCLUSIONS: Patients with obstructive CRC have a reduced short-term overall survival. Also, long-term overall survival is impaired in patients who present with acute obstructive CRC compared to patients without obstruction.

Improving the Quality of MRI Reports of Preoperative Patients With Rectal Cancer: Effect of National Guidelines and Structured Reporting.

OBJECTIVE: Since the implementation of new guidelines for rectal cancer in The Netherlands in April 2014, clinical stage as seen at preoperative MRI indicates whether neoadjuvant therapy is necessary before rectal cancer surgery. Therefore, the importance of correct MRI interpretation has increased. The aim of this study was to evaluate the completeness of MRI reports of rectal cancer and the effect of implementation of the new guidelines and standardized reporting on the completeness of these reports. MATERIALS AND METHODS: Data were collected from all patients who consecutively underwent rectal cancer surgery at one hospital between January 2011 and July 2017. Data were extracted from electronic patient records. RESULTS: The study included 492 MRI examinations. Before implementation of the new guidelines, a median of 4 of 10 items (interquartile range [IQR], 3-6 items) were described in each MRI report. After implementation of the new guidelines, the number of items described improved significantly (median, 7 items; IQR, 6-8 items; p < 0.001). Implementation of a standardized report led to further significant improvement (median, 9 items; IQR, 9-10 items; p < 0.001). The items scored most frequently were distance between the tumor and the anal verge (85.6%) and length of the tumor (87.6%). The items scored least were presence or absence of extramural venous invasion (21.1%) and morphologic features of the tumor (24.6%). CONCLUSION: Implementation of a standardized protocol and a standardized reporting system for MRI in preoperative staging of rectal cancer results in a more complete MRI report.

Direct access to magnetic resonance imaging improved orthopaedic knee referrals in the Netherlands.

BACKGROUND: The use of magnetic resonance imaging (MRI) in primary care is under debate, and the majority of GPs have no experience with MRI. OBJECTIVES: To examine for which patients with knee injury an MRI is ordered and does direct access to MRI in primary care influence the GP referral to an orthopaedic surgeon? METHODS: Consecutive patients with knee injury who underwent an MRI examination ordered by their GP were included. On the application form for MRI, the GPs indicated their referral intention in advance, as if MRI had not been available. Six months after the MRI scan, written interviews with the GPs were used to collect data on referrals and orthopaedic intervention. The number of patients finally referred to an orthopaedic surgeon in secondary care after MRI was compared with the number of intended referrals. RESULTS: Of the 588 included, GPs referred fewer patients to the orthopaedic surgeon after receiving the MRI results than they would have done prior to MRI (60% versus 82.8%, P < 0.0001). The reduction was 16.1% for patients older than 50 years and 28.1% for patients younger than 50 years. Orthopaedic intervention was performed in 62.9% of all referred patients. Of the 101 patients whom the GP did not intend to refer prior to MRI, 48 were referred to an orthopaedic surgeon based on the MRI findings. CONCLUSION: In patients with knee injury, direct access to MRI of the knee in a primary care setting significantly reduced referrals to an orthopaedic surgeon. LEVEL OF EVIDENCE: Three prospective cohort.

Cost-effectiveness of screening strategies to detect heart failure in patients with type 2 diabetes.

BACKGROUND: Heart failure (HF), especially with preserved ejection fraction (HFpEF) is common in older patients with type 2 diabetes (T2DM), but often not recognized. Early HF detection in older T2DM patients may be worthwhile because treatment may be initiated in an early stage, with clear beneficial treatment in those with reduced ejection fraction (HFrEF), but without clear prognostic beneficial treatment in those with HFpEF. Because both types of HF may be uncovered in older T2DM, screening may improve health outcomes at acceptable costs. We assessed the cost-effectiveness of five screening strategies in patients with T2DM aged 60 years or over. METHODS: We built a Markov model with a lifetime horizon based on the prognostic results from our screening study of 581 patients with T2DM, extended with evidence from literature. Cost-effectiveness was calculated from a Dutch healthcare perspective as additional costs (Euros) per additional quality-adjusted life-year (QALY) gained. We performed probabilistic sensitivity analysis to assess robustness of these outcomes. Scenario analyses were performed to assess the influence of the availability of effective treatment of heart failure with preserved ejection fraction. RESULTS: For willingness to pay values in the range of €6050/QALY-€31,000/QALY for men and €6300/QALY-€42,000/QALY for women, screening-based checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms had the highest probability of being cost-effective. For higher willingness-to-pay values, direct echocardiography was the preferred screening strategy. Cost-effectiveness of all screening strategies improved with the increase in effectiveness of treatment for HFpEF. CONCLUSIONS: Screening for HF in older community-dwelling patients with T2DM is cost-effective at the commonly used willingness-to-pay threshold of €20.000/QALY by checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms. The simplicity of such a strategy makes it feasible for implementation in existing primary care diabetes management programs.

[High prevalence of vitamin D deficiency in the south-west Netherlands]. / Hoge prevalentie van vitamine D-deficiëntie in Zuidwest-Nederland.

OBJECTIVE: To determine how often vitamin D deficiency occurs in the populations of a city, the countryside and urbanised areas of the countryside, and also the influence of the seasons. DESIGN: Cross-sectional study carried out in the winter and summer of 2013. Trend analysis from requests for determination of vitamin D levels by general practitioners between January 2010 and August 2012. METHOD: In a random sample survey of all blood samples received by SHL-Groep (diagnostic center for primary care) between 21-01-2013 - 10-03-2013 (winter period) and 01-08-2013 - 30-08-2013 (summer period), Vitamin D levels of the residual material were measured. We reported the results by age group, gender and postal code area in the following areas: The Hague (city), Province of Zeeland (countryside) and West Brabant (urbanised countryside). In addition, the average vitamin D concentration obtained from all the requests for determination of vitamin D levels between January 2010 and August 2012 was measured against the time of year. RESULTS: During the winter period 58.8% of the 2503 participants had a vitamin D serum concentration of < 50 nmol/l (The Hague: 65.6%; Zeeland: 50.9%). A total of 29.9% had vitamin D levels of < 30 nmol/l. In men under the age of 50 years, this was 38.2%. Of the 1910 people tested during the summer, 35.4% had a vitamin D level of < 50 nmol/l (The Hague: 43.7%; Zeeland: 33.5%). 11.6% had a vitamin D level < 30 nmol/l. General practitioners requested the vitamin D levels of 50,441 patients. The average vitamin D level varies considerably with the seasons. CONCLUSION: Vitamin D deficiency occurs frequently, even in relatively young people and more so in cities than in the countryside. The average vitamin D concentration varies with the seasons.

Efficiently screening heart failure in patients with type 2 diabetes.

AIMS: Our aim was to develop a screening tool for heart failure in patients with type 2 diabetes. METHODS AND RESULTS: A total of 581 consecutive patients from 21 primary care practices in The Netherlands with type 2 diabetes, in whom the diagnosis of heart failure (HF) was not known, underwent an extensive diagnostic assessment, including medical history taking, physical examination, ECG, and echocardiography. The presence or absence of HF was established by a panel of two cardiologists and one general practitioner following the guidelines on HF of the European Society of Cardiology. In 161 patients, HF was considered present. A model based on the medical history and symptoms had a good discriminative value for detecting or excluding HF [C-statistic after bootstrapping 0.80; 95% confidence interval (CI) 0.76-0.83]. Adding signs improved the C-statistic to 0.82 (95% CI 0.79-0.86). A diagnostic screening score based on the clinical model had good discriminative properties applying a cut-off of 3 points (24.7% risk of HF) with sensitivity 70.8%, specificity 79.0%, negative predictive value 87.6%, and positive predictive value 56.4%. ECG and natriuretic peptides both had independent added value beyond the clinical model and increased the C-statistic to 0.86 (95% CI 0.83- 0.89). With a 20% threshold, the net reclassification of adding ECG and NT-proBNP to the clinical model was only 0.06. CONCLUSIONS: A decision aid based on items from the clinical assessment is useful for screening HF in older patients with type 2 diabetes and to pre-select for echocardiography. TRIAL REGISTRATION: NL2271704108.

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2).

BACKGROUND: We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely. PRIMARY OBJECTIVES: - To assess the prevalence of (previously unrecognised) heart failure in primary care patients with diabetes type 2.- To establish the most cost-effective diagnostic strategy to detect unrecognised heart failure in these patients. SECONDARY OBJECTIVES: - To assess the impact of heart failure, and the combination of a new diagnosis with accordingly treatment in patients with diabetes type 2 on health status. DESIGN: A prospective diagnostic efficiency study. PATIENT POPULATION: Patients aged 60 years and older with diabetes type 2 from primary care, enlisted with the diabetes service of the Diagnostic Center in Etten-Leur (SHL)All participants will be investigated at the cardiology out-patient department of the regional hospital (Oosterschelde Hospital in Goes, Zeeland, the Netherlands) during a single 1.5 hour standardised diagnostic assessment, including history taking, physical examination, electrocardiography, echocardiography, blood tests, and Health status questionnaires. Patients will be asked if we can contact them afterwards for follow-up and for repeating the questionnaires after three and 12 months.Main study parameters/endpoints: Prevalence (with exact 95% confidence intervals) of (previously unrecognised) heart failure (systolic and 'isolated' diastolic) and the diagnostic value of signs and symptoms, NT-proBNP, electrocardiography and a combination of these items. The cost-effectiveness of different diagnostic strategies. Impact of heart failure and the combination of a new diagnosis with accordingly treatment on health status. TRIAL REGISTRATION: CCMO register NL2271704108.

An expert-supported monitoring system for patients with chronic obstructive pulmonary disease in general practice: results of a cluster randomised controlled trial.

OBJECTIVE: To investigate the long-term effectiveness of a general practice monitoring system with respiratory expert recommendations for general practitioners' management of patients with chronic obstructive pulmonary disease (COPD), compared with usual care. DESIGN, SETTINGS AND PARTICIPANTS: A multicentre randomised controlled trial of patients with COPD, clustered by general practices; 200 participants were recruited to maintain at least 75 participants per group for analysis. The trial took place from July 2005 to February 2008 in the south-western region of the Netherlands. INTERVENTION: Ongoing half-yearly monitoring of COPD patients with respiratory expert recommendations for the GP was compared with usual care. MAIN OUTCOME MEASURES: Primary outcome - Chronic Respiratory Questionnaire (CRQ) score; secondary outcomes - CRQ domain scores, generic health-related quality of life (Short-Form 12 and EuroQol-5D), breathlessness (Modified Medical Research Council score), exacerbations, and decline in forced expiratory volume in 1 second. A detailed process evaluation was performed along with the trial. RESULTS: Data from 170 participants were analysed. Based on repeated measurement analyses, the additional gain in CRQ score during follow-up was 0.004 points for monitoring compared with usual care (95% CI, - 0.172 to 0.180). Also, no important differences between monitoring and the usual care group were found for secondary outcomes. Half the monitoring visits resulted in disease management recommendations by a respiratory expert, and 46% of these recommendations were implemented by the GPs. Patient adherence to lifestyle recommendations was low. CONCLUSION: An expert-supported monitoring system for patients with COPD was not clinically effective. As patients had a pre-existing entry in the monitoring system, the population may be well regulated, with reduced room for improvement. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00542061.

Preanalytical variables and off-site blood collection: influences on the results of the prothrombin time/international normalized ratio test and implications for monitoring of oral anticoagulant therapy.

BACKGROUND: The quality of oral anticoagulant therapy management with coumarin derivatives requires reliable results for the prothrombin time/International Normalized Ratio (PT/INR). We assessed the effect on PT/INR of preanalytical variables, including ones related to off-site blood collection and transportation to a laboratory. METHODS: Four laboratories with different combinations of blood collection systems, thromboplastin reagents, and coagulation meters participated. The simulated preanalytical variables included time between blood collection and PT/INR determinations on samples stored at room temperature, at 4-6 degrees C, and at 37 degrees C; mechanical agitation at room temperature, at 4-6 degrees C, and at 37 degrees C; time between centrifugation and PT/INR determination; and times and temperatures of centrifugation. For variables that affected results, the effect of the variable was classified as moderate when <25% of samples showed a change >10% or as large if >25% of samples showed such a change. RESULTS: During the first 6 h after blood collection, INR changed by >10% in <25% of samples (moderate effect) when blood samples were stored at room temperature, 4-6 degrees C, or 37 degrees C with or without mechanical agitation and independent of the time of centrifugation after blood collection. With one combination of materials and preanalytical conditions, a 24-h delay at room temperature or 4-6 degrees C had a large effect, i.e., changes >10% in >25% of samples. In all laboratories, a 24-h delay at 37 degrees C or with mechanical agitation had a large effect. We observed no clinically or statistically relevant INR differences among studied centrifugation conditions (centrifugation temperature, 20 degrees C or no temperature control; centrifugation time, 5 or 10 min). CONCLUSIONS: We recommend a maximum of 6 h between blood collection and PT/INR determination. The impact of a 24-h delay should be investigated for each combination of materials and conditions.