Patients risk for mortality at 90 days after proximal femur fracture - a retrospective study in a tertiary care hospital.

BACKGROUND: Despite improving the management of proximal femur fractures (PFF) with legal requirements of timing the surgery within 24 h, mortality rates in these patients remain still high. The objective of our study was to analyze potential cofactors which might influence the mortality rate within 90 days after surgery in PFF to avoid adverse events, loss of quality of life and high rates of mortality. METHODS: In this retrospective, single-center study all patients with PFF aged 65 years and older were included. We recorded gender, age, type of fracture, surgery and anesthesia, time, comorbidities and medication as well as complications and mortality rate at 90 days. Separate logistic regression models were used to assess which parameters were associated with patients' mortality. The mortality rate was neither associated with timing, time and type of surgery nor time and type of anesthesia, but with higher age (OR 1.08 per year; 95% CI 1.034-1.128), lower BMI (OR 0.915 per kg/m2; 95% CI 0.857-0.978), higher CCI (OR 1.170 per point; 95% CI 1.018-1.345), dementia (OR 2.805; 95% CI 1.616-4.869), non-surgical complications (OR 2.276; 95% CI 1.269-4.083) and if mobilization was impossible (OR 10.493; 95% CI 3.612-30.479). RESULTS: We analyzed a total of 734 patients (age ≥ 65 years) who had a PFF in 2019 and 2020 and received surgery. 129 patients (17.6%) died until 90 days at an median age of 89.7 years (range 65-101 years). CONCLUSION: The proportion of patients who died until 90 days after surgery is still high. It is less extend influenced by surgical and anaesthesiologic factors than by patient-related factors like age or lower BMI. Physicians should be aware of the importance of avoiding adverse events and the importance of patients' mobilization to reduce mortality and improve patients' outcome.

Accelerate postoperative management after scoliosis surgery in healthy and impaired children: intravenous opioid therapy versus epidural therapy.

PURPOSE: Postoperative pain is a major concern following scoliosis surgery. CEA (continuous epidural analgesia) is established in postoperative pain therapy as well as intravenous patient-controlled analgesia (IV-PCA). The purpose of this study was to compare the clinical outcomes of both methods. METHODS: We retrospectively studied 175 children between 8 and 18 years who were subject to posterior scoliosis correction and fusion. Two main cohorts were formed: CEA with local anesthetic and opioids, and IV-PCA with opioids. Both groups further comprised two sub-cohorts: those who were mentally and/or physically healthy (H; n = 93 vs. n = 30) and those who were impaired (I; n = 26 vs. n = 26). The outcome parameters were the demand for pain medication, parameters of mobilization, and the presence of adverse reactions. RESULTS: Healthy children who received CEA started mobilization 1 day earlier than children with IV-PCA (p = 0.002). First postsurgical defecation was seen earlier in all children who received CEA in both groups (H; Day 4 vs. Day 5, p = 0.011, I; Day 3 vs. Day 5, p = 0.044). Healthy children who received CEA were discharged from hospital 4 days earlier than their IV-PCA counterparts (p < 0.001). No statistically significant difference in postoperative nausea nor in vomiting was identified between groups. Transient neurological irritations were seen in 9.7% of the patients in the CEA group. CONCLUSIONS: CEA provides appropriate pain management after scoliosis surgery, regardless of the patient's mental status. It allows earlier postoperative defecation for all patients , as well as shorter hospitalization and an earlier mobilization for healthy patients.

Predictive ability of viscoelastic testing using ClotPro® for short-term outcome in patients with severe Covid-19 ARDS with or without ECMO therapy: a retrospective study.

BACKGROUND: SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann-Whitney U test. RESULTS: Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350-560) vs 359 s (IQR 287-521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p < 0.05), FIB-test (35 vs 24 mm, p < 0.05) and TPA-test (52 vs 36 mm, p < 0.05) as well as higher values of inflammatory markers (CRP, PCT and IL6). ECMO patients suffered more frequently from bleeding complications (32% vs 15%). CONCLUSION: Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease.

Impact of self-coiling catheters for continuous popliteal sciatic block on postoperative pain level and dislocation rate: a randomized controlled trial.

BACKGROUND: Dislocation of catheters within the tissue is a challenge in continuous regional anesthesia. A novel self-coiling catheter design is available and has demonstrated a lower dislocation rate in a cadaver model. The dislocation rate and effect on postoperative pain of these catheters in vivo has yet to be determined and were the subjects of this investigation. METHODS: After ethics committee approval 140 patients undergoing elective distal lower limb surgery were enrolled in this prospective randomized controlled trial. Preoperatively, patients were randomly assigned and received either the conventional (n = 70) or self-coiling catheter (n = 70) for ultrasound-guided popliteal sciatic nerve block in short axis view and by the in-plane approach from lateral to medial. The primary outcome was pain intensity after surgery and on the following three postoperative days. Secondary outcomes investigated were dislocation rate in situ determined by sonography, catheter movement visible from outside, opioid consumption as well as leakage at the puncture site. RESULTS: All catheters were successfully inserted. The study population of self-coiling catheters had significantly lower mean numeric rating scale values than the reference cohort on the first (p = 0.01) and second postoperative days (p < 0.01). Sonographic evaluation demonstrated, 42 standard catheters (60%) and 10 self-coiling catheters (14.3%) were dislocated in situ within the first three postoperative days. The externally visible movement of the catheters at insertion site did not differ significantly between groups through the third postoperative day. The opioid consumption was significantly lower in the self-coiling catheter group on the day of surgery and on the second and third postoperative days (p = 0.04, p = 0.03 and p = 0.04, respectively). CONCLUSION: The self-coiling catheter offers a better postoperative pain control and a lower dislocation rate within the tissue when blocking the popliteal sciatic nerve compared to a conventional catheter. Further trials in large patient cohorts are warranted to investigate the potential beneficial effects of self-coiling catheters for other localisations and other application techniques. TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (DRKS) on 08/04/2020 ( DRKS00020938 , retrospectively registered).

Prolonged Catheter Use and Infection in Regional Anesthesia: A Retrospective Registry Analysis.

BACKGROUND: Prolonged catheter use is controversial because of the risk of catheter-related infection, but the extent to which the risk increases over time remains unknown. We thus assessed the time-dependence of catheter-related infection risk up to 15 days. METHODS: Our analysis was based on the German Network for Regional Anesthesia, which includes 25 centers. We considered 44,555 patients who had surgery between 2007 and 2014 and had continuous regional anesthesia as well as complete covariable details. Cox regression analysis was performed and adjusted for confounding covariables to examine the relationship between catheter duration and probability of infection-free catheter use. RESULTS: After adjustment for confounding factors, the probability of infection-free catheter use decreases with each day of peripheral and epidural catheter use. In peripheral catheters, it was 99% at day 4 of catheter duration, 96% at day 7, and 73% at day 15. In epidural catheters, it was 99% at day 4 of catheter duration, 95% at day 7, and 73% at day 15. Only 31 patients (0.07%) had severe infections that prompted surgical intervention. Among these were five catheters that initially had only mild or moderate signs of infection and were left in situ; all progressed to severe infections. CONCLUSIONS: Infection risk in catheter use increases over time, especially after four days. Infected catheters should be removed as soon as practical. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B683.

Risks and Benefits of Ultrasound, Nerve Stimulation, and Their Combination for Guiding Peripheral Nerve Blocks: A Retrospective Registry Analysis.

BACKGROUND: Ultrasound, nerve stimulation, and their combination are all considered acceptable ways to guide peripheral nerve blocks. Which approach is most effective and associated with the fewest complications is unknown. We therefore used a large registry to analyze whether there are differences in vascular punctures, multiple skin punctures, and unintended paresthesia. METHODS: Twenty-six thousand seven hundred and thirty-three cases were extracted from the 25-center German Network for Regional Anesthesia registry between 2007 and 2016 and grouped into ultrasound-guided puncture (n = 10,380), ultrasound combined with nerve stimulation (n=8173), and nerve stimulation alone (n = 8180). The primary outcomes of vascular puncture, multiple skin punctures, and unintended paresthesia during insertion were compared with conditional logistic regression after 1:1:1 propensity score matching. Results are presented as odds ratios and 95% CIs. RESULTS: Propensity matching successfully paired 2508 patients with ultrasound alone (24% of 10,380 patients), 2508 patients with a combination of ultrasound/nerve stimulation (31% of 8173 patients), and 2508 patients with nerve stimulation alone (31% of 8180 patients). After matching, no variable was imbalanced (standardized differences <0.1). Compared with ultrasound guidance alone, the odds of multiple skin punctures (2.2 [1.7-2.8]; P < .001) and vascular puncture (2.7 [1.6-4.5]; P < .001) were higher with nerve stimulation alone, and the odds for unintended paresthesia were lower with nerve stimulation alone (0.3 [0.1-0.7]; P = .03). The combined use of ultrasound/nerve stimulation showed higher odds of multiple skin punctures (1.5 [1.2-1.9]; P = .001) and lower odds of unintended paresthesia (0.4 [0.2-0.8]; P = .007) compared with ultrasound alone. Comparing the combined use of ultrasound/nerve stimulation with ultrasound alone, the odds for vascular puncture (1.3 [0.7-2.2]; P = .4) did not differ significantly. Systemic toxicity of local anesthetics was not observed in any patient with ultrasound guidance alone, in 1 patient with the combined use of ultrasound and nerve stimulation, and in 1 patient with nerve stimulation alone. CONCLUSIONS: Use of ultrasound alone reduced the odds of vascular and multiple skin punctures. However, the sole use of ultrasound increases the odds of paresthesia.

[Prehospital ultrasound in emergency medicine]. / Prähospitaler Ultraschall in der Notfallmedizin.

Small, portable hand-held ultrasound devices nowadays enable a widespread use of prehospital point-of-care ultrasound (pPOCUS), which has so far only been used hesitantly, especially in ground-based emergency services. Many critical or even life-threatening conditions or internal injuries can often be better diagnosed or ruled out using pPOCUS, which can enable faster and more suitable goal-directed treatment and hospital transport. This article critically discusses relevant data, clinical benefits, limitations and challenges to be overcome when using pPOCUS for the most important life-threatening situations and aims to call for intensifying training and the extensive use of pPOCUS.

Bleeding management in patients with direct oral anticoagulants.

Bleeding events in patients under direct oral anticoagulation (DOAC) can be life-threating but are commonly not related to drug overdose. However, a relevant DOAC plasma concentration impairs the hemostasis and should therefore be ruled out immediately after hospital admission. The effect of DOAC is typically not visible in standard coagulation tests such as activated partial thrombin time or thromboplastin time. Specific anti-Xa or anti-IIa assays allow a specific drug monitoring, but they are too time-consuming in critical bleeding events and typically not available 24 h/7 d in routine care. Recent advantages in point-of-care (POC) testing might improve patient care by early exclusion of relevant DOAC levels, but sufficient validation is still lacking. POC urine analysis help to exclude DOAC in emergency patients, but does not provide a quantitative information about plasma concentration. POC viscoelastic testing (VET) can determine the DOAC effect on clotting time and helps further to reveal other concomitant bleeding disorders in emergency, e.g., factor deficiency or hyperfibrinolysis. If a relevant plasma concentration of the DOAC is assumed or was proven by either laboratory assays or POC testing, restoration of factor IIa or factor IIa activity is key for effective hemostasis. Limited evidence suggests that specific reversals for DOAC, e.g., idarucizumab for dabigatran and andexanet alfa for apixaban or rivaroxaban, might be superior to increasing thrombin generation by administration of prothrombin complex concentrates. To determinate, if DOAC reversal is indicated or not, time from last intake, anti-Xa/dTT values or results from POC tests can be considered. This experts' opinion provides a feasible decision algorithm for clinical practice.

Point of care coagulation management in anesthesiology and critical care.

Point of care (POC) devices are increasingly used in the ICU and in anesthesia. Besides POC-devices for blood gas analysis, several devices are available for coagulation measurements. Although basic principles for thromboelastographic measurements are not novel, some promising developments were made during the last decade improving both user-friendliness and measurement reliability. For instance, POC measurements of activated clotting time (ACT) for heparin monitoring is still regarded as standard-of-care in cardiac interventions and surgery. In the field of anesthesia and intensive care medicine, POC-devices for thromboelastographic and platelet aggregation measurements are widely used. Their impact in case of bleeding and patient blood management for cardiothoracic and trauma surgery is well known. Moreover, there are promising concepts for anticoagulation monitoring including new oral anticoagulant drugs. Coagulation POC-devices may also identify patients at specific risk for thromboembolic events quickly. On the other hand, benefits of POC-devices need to be balanced against limitations, which include technical restrictions and operator related errors, mainly affecting reproducibility and interpretation of results. Therefore, it is recommendable to consider results of POC-coagulation testing in comparison to standard laboratory tests (SLT). Nevertheless, in urgent or emergency situations POC results enable fast decision making to optimize patient care.

Enhancing Anticoagulation Monitoring and Therapy in Patients Undergoing Microvascular Reconstruction in Maxillofacial Surgery: A Prospective Observational Trial.

BACKGROUND: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. OBJECTIVE: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. METHODS/DESIGN: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. DISCUSSION: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.

Influence of Anatomic Conditions on Efficacy and Safety of Combined Intermediate Cervical Plexus Block and Perivascular Infiltration of Internal Carotid Artery in Carotid Endarterectomy: A Prospective Observational Trial.

Ultrasound-guided intermediate cervical plexus blockade with perivascular infiltration of the carotid artery bifurcation perivacular block (PVB) is a reliable technique for regional anesthesia in carotid endarterectomy (CEA). We investigated the effect of the carotid bifurcation level (CBL) on PVB efficacy and safety in patients undergoing CEA. This prospective observational cohort study included 447 consecutive CEA patients who received PVB over a 6-y period. Vascular and neurologic puncture-related complications were recorded. The CBL was localized at the low level (C4 and C5 vertebra, low-level [LL] group) in 381 (85.2%) patients and at the high level (C2 and C3 vertebra, high-level [HL] group) in 66 (14.8%) patients. Local anesthetic supplementation by surgeons was necessary in 64 (14.3%) patients in the LL group and 38 (59.4%) patients in the HL group (p < 0.001) and was associated with a higher rate of central neurologic complications in the HL group (p = 0.031). Therefore, the efficacy of the PVB may be influenced by the CBL.

Precision of traditional approaches for lumbar plexus block: impact and management of interindividual anatomic variability.

BACKGROUND: Traditional methods for approaching the lumbar plexus from the posterior rely on finding the intersection of lines that are drawn based on surface landmarks. These methods may be inaccurate in many cases. The aim of this study was to determine the accuracy of these traditional approaches and determine if modifications could increase their accuracy. METHODS: The lumbar plexus region of 48 cadavers (78 +/- 7 yr; 167 +/- 6 cm; 60 +/- 13 kg; men/women: 29/19) was dissected, and relevant anatomic structures were marked. Needle proximity curves were obtained by triangulation for the five traditional approaches and for vectors from the posterior superior iliac spine directed towards the lumbar spinous processes of L3 and towards L4. RESULTS: Proximity curves (mean +/- SD) showed that except Pandin's approach (13 +/- 5 mm too medial), all others were too lateral: Winnie (17 +/- 8 mm), Chayen (8 +/- 5 mm), Capdevila (6 +/- 4 mm), and Dekrey (17 +/- 6 mm). Further, the curves had a narrow parabolic shape and thus a narrow margin of error. Both diagonal vectors had a significantly higher proximity to the lumbar plexus as compared with traditional approaches with a wide parabola, indicating more error tolerance. Using the vector posterior superior iliac spine-L3 with a length between 1/6-1/3 (= 16-22 mm) of the distance posterior superior iliac spine-L3, a proximity to the lumbar plexus < 5.0 +/- 0.3 mm was reached. CONCLUSION: Improvement of both the proximity and the margin of error is possible by using diagonal landmark vectors. Relying on the position of the posterior superior iliac spine eliminates the sex and sided differences and individual body size, which can be problematic if firm metric distances are used in determining the entry point.

[A German network for regional anaesthesia of the scientific working group regional anaesthesia within DGAI and BDA]. / Das Netzwerk Regionalanästhesie des wissenschaftlichen Arbeitskreises Regionalanästhesie der DGAI und des BDA.

Regional anaesthesia generally is considered to be safe. However, reports of complications with different severities are also well known. The scientific working group of regional anaesthesia of the DGAI has founded a network in conjunction with the BDA. With the aid of a registry, we are now able to describe risk profiles and associations in case of a complication. Moreover, a benchmark has been implemented in order to continuously improve complication rates.

Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia.

INTRODUCTION: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse. METHODS AND ANALYSIS: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. ETHICS AND DISSEMINATION: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals. TRIAL REGISTRATION NUMBER: DRKS00013644; Pre-results.

Psoas Versus Femoral Blocks: A Registry Analysis of Risks and Benefits.

BACKGROUND AND OBJECTIVES: Psoas blocks are an alternative to femoral nerve blocks and have the potential advantage of blocking the entire lumbar plexus. However, the psoas muscle is located deeply, making psoas blocks more difficult than femoral blocks. In contrast, while femoral blocks are generally easy to perform, the inguinal region is prone to infection. We thus tested the hypothesis that psoas blocks are associated with more insertion-related complications than femoral blocks but have fewer catheter-related infections. METHODS: We extracted 22,434 surgical cases from the German Network for Regional Anesthesia registry (2007-2014) and grouped cases as psoas (n = 7593) and femoral (n = 14,841) blocks. Insertion-related complications (including single-shot blocks and catheter) and infectious complications (including only catheter) in each group were compared with χ tests. The groups were compared with multivariable logistic models, adjusted for potential confounding factors. RESULTS: After adjustment for potential confounding factors, psoas blocks were associated with more complications than femoral blocks including vascular puncture 6.3% versus 1.1%, with an adjusted odds ratio (aOR) of 3.6 (95% confidence interval [CI], 2.9-4.6; P < 0.001), and multiple skin punctures 12.6% versus 7.7%, with an aOR of 2.6 (95% CI, 2.1-3.3; P <0.001). Psoas blocks were also associated with fewer catheter-related infections: 0.3% versus 0.9% (aOR of 0.4; 95% CI, 0.2-0.8; P = 0.016), and with improved patient satisfaction (mean ± SD 0- to 10-point scale score, 9.6 ± 1.2 vs 8.4 ± 2.9; P < 0.001). Results from a propensity-matched sensitivity analysis were similar. CONCLUSIONS: Psoas blocks are associated with more insertion-related complications but fewer infectious complications. CLINICAL TRIAL REGISTRATION: ID NCT02846610.

Misplacement of a psoas compartment catheter in the subarachnoid space.

BACKGROUND AND OBJECTIVES: This case report describes an unusual cause of misplacement of an indwelling catheter in the subarachnoid space after primary psoas compartment block in a patient undergoing total knee arthroplasty. CASE REPORT: A 67-year-old woman presenting for total knee joint replacement received a combination of continuous psoas compartment block and sciatic nerve block. Neurostimulation and additional ultrasound guidance were used for identification of the lumbar plexus. After elicitation of a quadriceps motor response, a negative aspiration test, and an uneventful test dose, 20 mL ropivacaine 0.375% and 20 mL mepivacaine 1% were injected. Despite difficult ultrasound conditions because of intestinal air, local anesthetic spread was observed paravertebrally at the medial border of the psoas muscle as usual. A catheter was then advanced 7 cm through the insulated directional puncture needle. An additional sciatic nerve block was performed by using Labat's approach. Ten minutes after injection unilateral sensory block was noted and surgery was started. After uneventful surgery, bilateral sensory block to the T4 level and complete motor block in both lower limbs was detected. A second aspiration test was negative, and an epidural block was suspected. For verification of the catheter tip location, a computed tomography scan with contrast dye was performed revealing catheter placement in the subarachnoid space. The catheter was removed and showed a kink about 7 cm from the tip. After regression of the neuraxial block, lumbar plexus block persisted for another 2 hours. CONCLUSION: An additional test dose via the catheter is recommended if the indwelling catheter is inserted after injection of the local anesthetics through the puncture needle. If epidural anesthesia occurs, an x-ray of the catheter is advisable because negative aspiration via catheter does not rule out subarachnoid catheter location.