Post-COVID-19 recovery and geriatric rehabilitation care: a European inter-country comparative study.

PURPOSE: There is variation in organization of geriatric rehabilitation across Europe. The purpose of this study was to describe the selection criteria for referral to geriatric rehabilitation, care provided, and recovery trajectories of post-COVID-19 patients referred to geriatric rehabilitation in Europe. METHODS: This observational cohort study included 723 patients in 59 care facilities for geriatric rehabilitation across 10 countries. Patient data were collected from medical records on admission to geriatric rehabilitation (between September 2020 and October 2021), discharge, 6 weeks and 6 months follow-up. The primary and secondary outcomes were recovery in daily functioning (Barthel Index) and Quality of Life (EQ-5D-5L) from admission to discharge. These were examined using linear mixed models with two levels (measurements nested in patients) and country as an independent variable. Random intercept and random linear slope parameters were added when they improved model fit. A survey about organization of geriatric rehabilitation for post-COVID-19 patients was filled out by country coordinators and data were analyzed using descriptive statistics and inductive coding of answers to open questions. RESULTS: Patients had a mean age of 75.7 years old and 52.4% were male. Many countries used various combinations of the selection criteria, such as functional status, age, frailty, Comprehensive Geriatric Assessment, comorbidities, and cognitive impairments. Most patients received physiotherapy (88.8%) and occupational therapy (69.7%), but there was substantial variance between countries in the percentages of patients that received protein or calorie enriched diets, oxygen therapy, and other treatment components. In all countries, patients showed recovery in daily functioning and quality of life, although there was variation in between countries in rate of recovery. Daily functioning seemed to increase most rapidly in the Czech Republic, Germany, and Russia. The steepest increases in quality of life were seen in the Czech Republic, Germany, and Spain. CONCLUSION: Post-COVID-19 patients showed recovery during geriatric rehabilitation, albeit at variable rates. The observed variation may be explained by the heterogeneity in selection criteria and care provided. This study highlights the need for harmonization of measurements in geriatric rehabilitation order to perform explanatory research and optimize geriatric rehabilitation throughout Europe to ensure optimal patient recovery.

Long-term outcomes of older adults with acute COVID-19 following inpatient geriatric rehabilitation: a prospective cohort study from the Republic of Ireland.

BACKGROUND: There is a paucity of research reporting the long-term outcomes of older adults who have completed geriatric rehabilitation following COVID-19. AIM: The primary aim of this study is to describe the long-term functional outcomes of a cohort of older adults with acute COVID-19 who have completed inpatient geriatric rehabilitation. METHODS: This is a subgroup analysis of Irish data from a pan-European prospective cohort study. Functional ability, patient reported symptoms, and quality of life were measured using the Barthel index, the COVID-19 Yorkshire Rehabilitation Screen, and the EQ-5D-5L, respectively. RESULTS: Thirty patients enrolled in the study. The rate of mortality was 23.3% at 6 months after discharge from rehabilitation. Patients achieved a return to pre-admission functional ability but reported a significant increase in patient reported symptoms and their quality of life did not return to pre-admission levels when assessed at 6 months after discharge from rehabilitation. CONCLUSIONS: Multidisciplinary rehabilitation for older adults with acute COVID-19 infection can assist patients to return to their premorbid functional ability. On discharge from rehabilitation, ongoing follow-up of older adults is recommended to assist them to negotiate and manage ongoing symptomatology such as breathlessness or fatigue.

Post-COVID-19 patients in geriatric rehabilitation substantially recover in daily functioning and quality of life.

BACKGROUND: After an acute infection, older persons may benefit from geriatric rehabilitation (GR). OBJECTIVES: This study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery. DESIGN: Multicentre prospective cohort study. SETTING: 59 GR facilities in 10 European countries. PARTICIPANTS: Post-COVID-19 patients admitted to GR between October 2020 and October 2021. METHODS: Patients' characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL. RESULTS: 723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0-7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: -0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: -0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients. CONCLUSIONS: Post-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR.

Core requirements of frailty screening in the emergency department: an international Delphi consensus study.

INTRODUCTION: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study. METHODS: A two-round electronic Delphi involving 37 participants from 10 countries was undertaken. Statements were generated from a prior systematic review examining frailty screening instruments in ED (logistic, psychometric and clinimetric properties). Reflexive thematic analysis generated a list of 56 statements for Round 1 (August-September 2021). Four main themes identified were: (i) principles of frailty screening, (ii) practicalities and logistics, (iii) frailty domains and (iv) frailty risk factors. RESULTS: In Round 1, 13/56 statements (23%) were accepted. Following feedback, 22 new statements were created and 35 were re-circulated in Round 2 (October 2021). Of these, 19 (54%) were finally accepted. It was agreed that ideal frailty screens should be short (<5 min), multidimensional and well-calibrated across the spectrum of frailty, reflecting baseline status 2-4 weeks before presentation. Screening should ideally be routine, prompt (<4 h after arrival) and completed at first contact in ED. Functional ability, mobility, cognition, medication use and social factors were identified as the most important variables to include. CONCLUSIONS: Although a clear consensus was reached on important requirements of frailty screening in ED, and variables to include in an ideal screen, more research is required to operationalise screening in clinical practice.

Call to action: a five nations consensus on the use of intravenous zoledronate after hip fracture.

Currently in the UK and Ireland, after a hip fracture most patients do not receive bone protection medication to reduce the risk of refracture. Yet randomised controlled trial data specifically examining patients with hip fracture have shown that intravenous zoledronate reduces refracture risk by a third. Despite this evidence, use of intravenous zoledronate is highly variable following a hip fracture; many hospitals are providing this treatment, whilst most are currently not. A range of clinical uncertainties, doubts over the evidence base and practical concerns are cited as reasons. This paper discusses these concerns and provides guidance from expert consensus, aiming to assist orthogeriatricians, pharmacists and health services managers establish local protocols to deliver this highly clinically and cost-effective treatment to patients before they leave hospital, in order to reduce costly re-fractures in this frail population.

eHealth in Geriatric Rehabilitation: An International Survey of the Experiences and Needs of Healthcare Professionals.

While eHealth can help improve outcomes for older patients receiving geriatric rehabilitation, the implementation and integration of eHealth is often complex and time-consuming. To use eHealth effectively in geriatric rehabilitation, it is essential to understand the experiences and needs of healthcare professionals. In this international multicentre cross-sectional study, we used a web-based survey to explore the use, benefits, feasibility and usability of eHealth in geriatric rehabilitation settings, together with the needs of working healthcare professionals. Descriptive statistics were used to summarize quantitative findings. The survey was completed by 513 healthcare professionals from 16 countries. Over half had experience with eHealth, although very few (52 of 263 = 20%) integrated eHealth into daily practice. Important barriers to the use or implementation of eHealth included insufficient resources, lack of an organization-wide implementation strategy and lack of knowledge. Professionals felt that eHealth is more complex for patients than for themselves, and also expressed a need for reliable information concerning available eHealth interventions and their applications. While eHealth has clear benefits, important barriers hinder successful implementation and integration into healthcare. Tailored implementation strategies and reliable information on effective eHealth applications are needed to overcome these barriers.

Multidisciplinary inpatient rehabilitation for older adults with COVID-19: a systematic review and meta-analysis of clinical and process outcomes.

BACKGROUND: Older adults are at increased risk for disease severity and poorer prognosis following COVID-19 infection. The aim of this systematic review and meta-analysis is to explore the impact of multidisciplinary rehabilitation in the acute or post-acute hospital setting for older adults with COVID-19. METHODS: The Cochrane library, EMBASE, Cinahl and Medline (via EBSCO), PubMed, and Web of Science were systematically searched in June 2022 and a repeat search was completed in March 2023. Screening, data extraction and quality appraisal were conducted independently by two reviewers. Studies reporting outcomes for older adults following multidisciplinary rehabilitation (provided by two or more Health and Social Care Professionals) were included. Both observational and experimental study designs were included. The primary outcome was functional ability. Secondary outcomes included discharge disposition, acute hospital and rehabilitation unit length of stay, mortality, primary and secondary healthcare utilisation, and long-term effects of COVID-19. RESULTS: Twelve studies met the inclusion criteria, comprising a total of 570 older adults. Where reported, older adults stayed in the acute hospital for a mean of 18 days (95%CI, 13.35- 23.13 days) and in rehabilitation units for 19 days (95%CI, 15.88-21.79 days). There was a significant improvement in functional ability among older adults with COVID-19 who received multidisciplinary rehabilitation (REM, SMD = 1.46, 95% CI 0.94 to 1.98). The proportion of older adults who were discharged directly home following rehabilitation ranged from 62 to 97%. Two studies reported a 2% inpatient mortality rate of older persons during rehabilitative care. No study followed up patients after the point of discharge and no study reported on long term effects of COVID-19. CONCLUSIONS: Multidisciplinary rehabilitation may result in improved functional outcomes on discharge from rehabilitation units/centres for older adults with COVID-19. Findings also highlight the need for further research into the long-term effect of rehabilitation for older adults following COVID-19. Future research should comprehensively describe multidisciplinary rehabilitation in terms of disciplines involved and the intervention provided.

Management of post-acute COVID-19 patients in geriatric rehabilitation: EuGMS guidance.

PURPOSE: To describe a guidance on the management of post-acute COVID 19 patients in geriatric rehabilitation. METHODS: The guidance is based on guidelines for post-acute COVID-19 geriatric rehabilitation developed in the Netherlands, updated with recent insights from literature, related guidance from other countries and disciplines, and combined with experiences from experts in countries participating in the Geriatric Rehabilitation Special Interest Group of the European Geriatric Medicine Society. RESULTS: This guidance for post-acute COVID-19 rehabilitation is divided into a section addressing general recommendations for geriatric rehabilitation and a section addressing specific processes and procedures. The Sect. "General recommendations for geriatric rehabilitation" addresses: (1) general requirements for post-acute COVID-19 rehabilitation and (2) critical aspects for quality assurance during COVID-19 pandemic. The Sect. "Specific processes and procedures", addresses the following topics: (1) patient selection; (2) admission; (3) treatment; (4) discharge; and (5) follow-up and monitoring. CONCLUSION: Providing tailored geriatric rehabilitation treatment to post-acute COVID-19 patients is a challenge for which the guidance is designed to provide support. There is a strong need for additional evidence on COVID-19 geriatric rehabilitation including developing an understanding of risk profiles of older patients living with frailty to develop individualised treatment regimes. The present guidance will be regularly updated based on additional evidence from practice and research.

The ischaemic ECG: is it all in the head?

Acute cerebrovascular events including ischaemic stroke and subarachnoid haemorrhage are known to be associated with left ventricular dysfunction and significant electrocardiographic abnormalities that can mimic cardiac ischaemia. The authors present a case in which an intracerebral haemorrhage was diagnosed during the treatment of pneumonia in a 62-year-old woman, with repolarisation abnormalities on the ECG acting as the key diagnostic clue in the absence of clinical or radiological evidence of ventricular dysfunction. The pneumonia was treated without complication, and there were no long-term respiratory, cardiac or neurological sequelae. Diagnostic cardiac imaging, including angiography at follow-up, confirmed the absence of significant coronary artery disease, suggesting a non-coronary aetiology for these ECG changes. The authors emphasise that when presentation is atypical for acute coronary syndrome, non-specific ECG changes could point to a primary cerebrovascular pathology, even in the absence of neurological or cardiac symptoms.

Red cell distribution width is an independent predictor of mortality in hip fracture.

BACKGROUND: the red cell distribution width (RDW), an automated measure of variability in the red blood cell size on full blood count (FBC) is an independent predictor of mortality in several disease states and in healthy older people. OBJECTIVE: we wanted to determine the prognostic value of RDW in patients following a hip fracture-a condition associated with high mortality. DESIGN: we examined the relationship between admission RDW and mortality in 698 consecutive patients admitted with hip fracture. METHOD: regression analysis was used to examine admission RDW and subsequent mortality, adjusting for admission haemoglobin, mean corpuscular volume, age, gender, pre-morbid residence and independence level, Charlson co-morbidity index and post-operative complications. RESULTS: the mean age was 78 ± 13 years. Unadjusted 1-year mortality was 12, 15, 29 and 36% across quartiles of increasing RDW. Along with age and post-operative complications, RDW remained significantly associated with in-hospital, 120-day and 1-year mortality [adjusted hazard ratios: HR: 1.119, 95% CI: (1.000-1.253), P = 0.05, 1.134 (1.047-1.227), P = 0.004 and 1.131 (1.067-1.199), P < 0.001, respectively]. These relationships remained significant at all three time points on repeat analysis in non-anaemic patients (n = 548). CONCLUSION: RDW, a widely available parameter on FBC, is independently associated with an increased risk of short- and long-term mortality following hip fracture.

Refractory metabolic acidosis in patients with sepsis following hemiarthroplasty for femoral neck fracture: a causative role for paracetamol and flucloxacillin?

The authors report two cases of pyroglutamic acidosis as a result of paracetamol and flucloxacillin therapy in patients with prosthesis infection following hemiarthroplasty for neck of femur fractures. Pyroglutamic acidosis is an important and often unrecognised cause of refractory metabolic acidosis that disproportionately affects older women, and can be caused by drugs such as paracetamol and flucloxacillin in the setting of sepsis, renal failure and malnutrition. Although relatively rare, the widespread use of these drugs in orthopaedic patients confirms the importance of this disorder.

Effect of androgen suppression compared with androgen receptor blockade on arterial stiffness in men with prostate cancer.

Endogenous testosterone and estradiol are thought to be cardio-protective in men. We wanted to determine the effects of 2 different anti-androgen therapies on arterial stiffness as one suppresses (goserelin--a gonadotrophin-releasing hormone analog) while the other increases (bicalutamide--an androgen receptor blocker) both testosterone and estradiol. We conducted a randomized trial on 43 men (mean age, 71.2 +/- 6.2 years) with localized prostate cancer. They received either goserelin or bicalutamide for 24 weeks. Carotid-femoral (C-F) and carotid-radial (C-R) pulse wave velocities (PWVs) were measured. Twenty age- and disease-matched men with prostate cancer on no active treatment were studied in a similar manner. After 12 weeks of goserelin, radial artery PWV increased significantly from baseline and a nonsignificant increase was observed in femoral PWV (change from baseline radial: +1.4 m/s, P = .002, femoral: +0.9 m/s, P = .127) Both PWV measures increased significantly with bicalutamide (change from baseline radial: +0.8, femoral: +0.9 m/s, P or= .967 at 12 weeks and P >or= .07 at 24 weeks). The untreated men studied in parallel showed no changes at 12 or 24 weeks in either PWV measure. Anti-androgen treatment in men might increase large artery stiffness, an adverse cardiovascular risk factor; however, the effect was not maintained with testosterone receptor blockade, in the longer term, but tended to be sustained with suppression therapy. This could relate to the different sex hormone effects of the 2 therapies.

Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer.

OBJECTIVE: The aim of this study was to determine the effects of anti-androgens on left ventricular (LV) function and levels of N-terminal proB-type natriuretic peptide (NT-proBNP), a sensitive cardiac risk marker, in men with prostate cancer as these are widely used drugs in this condition, and evidence suggests that endogenous androgens are cardioprotective in men. DESIGN AND PATIENTS: Forty-three men (mean age 70.7 +/- 6.2 years) with prostate cancer were randomized to goserelin (an LH-releasing hormone analogue) or bicalutamide (an androgen-receptor blocker) for 6 months; 20 men with a history of prostate cancer on no treatment were studied in parallel. RESULTS: Mean changes in testosterone and oestradiol, respectively, from baseline to 6 months were -88% and -46% with goserelin, +50% and +44% with bicalutamide, and -1% and -9% for the 'no-treatment' group. Bicalutamide significantly increased NT-proBNP from baseline to 3 and 6 months (median value at baseline, 3 and 6 months: 55, 101 and 118 ng/l, respectively). Goserelin caused a significant increase from baseline to 3 months but not to 6 months (median value at baseline, 3 and 6 months: 66, 87 and 72 ng/l, respectively). No significant changes occurred in the 'no-treatment' cohort (median value at baseline 3 and 6 months: 60, 53 and 60 ng/l, respectively). No significant changes in LV function, blood pressure (BP), body mass index or waist-hip ratio occurred to account for the changes in NT-proBNP. CONCLUSION: Androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-pro-BNP in men with prostate cancer. The significance is not clear but could imply an adverse effect on cardiovascular risk following hormonal manipulation.

Increased arterial stiffness in Europeans and African Caribbeans with type 2 diabetes cannot be accounted for by conventional cardiovascular risk factors.

BACKGROUND: The impact of diabetes on vascular target organ damage (TOD) is not wholly explained by conventional risk factors. African Caribbeans have a greater prevalence of diabetes and some aspects of TOD. We hypothesized that arterial stiffness, an independent cardiovascular risk factor, would be more prevalent with diabetes and in African Caribbeans with diabetes than Europeans. METHODS: We measured pulse wave velocity (PWV), a measure of arterial stiffness, in the carotid-to-femoral, carotid-to-radial and femoral-to-dorsalis pedis segments, of men and women aged 40 to 65 years from the general population: 49 and 100 Europeans; 66 and 88 African Caribbeans with and without diabetes, respectively. RESULTS: Carotid-to-femoral PWV was faster (ie, arteries were stiffer) in diabetes and faster in African Caribbeans with diabetes compared with Europeans. These diabetes differences in PWV persisted after adjustment for conventional cardiovascular risk factors; Europeans without diabetes (95% confidence interval [CI]) 11.8 (11.4-12.3) versus with diabetes 13.3 (12.5-14.1) m/sec, P=.005; African Caribbeans without diabetes 12.6 (12.1-13.2) versus 14.0 (13.2-14.9) m/sec with diabetes, P=.008 (all fully adjusted). The ethnic difference in diabetes was largely attenuated by multivariate adjustment (P=.4). In the carotid-to-radial segment there was no ethnic difference in those without diabetes; however, African Caribbeans with diabetes had significantly faster PWV, which was not observed in Europeans (P for diabetes:ethnicity interaction=.001). CONCLUSIONS: Elastic arteries are stiffer in diabetes independent of traditional risk factors. African Caribbeans with diabetes have increased stiffness compared to Europeans, predominantly accounted for by blood pressure differences. Muscular arteries respond differently to diabetes in the two ethnic groups, which may reflect differences in remodeling.

Enhanced external counterpulsation does not alter arterial stiffness in patients with angina.

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive treatment for angina that acutely augments diastolic pressure and reduces cardiac afterload. However, the mechanism of the sustained clinical benefit seen with this therapy is not known. HYPOTHESIS: The study aimed to determine whether EECP leads to an improvement in arterial stiffness. METHODS: In all, 22 men and 1 woman with angina (age 63.6 +/- 6.7 years, mean +/- SD) were studied prior to and after 35 h of EECP therapy over 7 weeks. We measured carotid-radial (C-R) pulse wave velocity (PWV), and aortic augmentation index (AI) was derived from radial and carotid artery waveforms using applanation tonometry. Seventeen patients underwent treadmill exercise testing before and after the 7 weeks of EECP. RESULTS: After EECP therapy, despite a significant improvement in treadmill exercise time and a reduction in systolic and diastolic blood pressures, there was no significant change in any arterial stiffness parameters: Mean C-R PWV was 8.4 +/- 0.8 m/s at baseline and 8.0 +/- 1.2 m/s after 7 weeks of EECP, mean change: -0.4, 95% confidence interval (CI): -1.0, + 0.2, p = 0.17. Mean radial-derived AI was 25.7 +/- 10.4% before and 24.6 +/- 10.8% after, mean change: +1.1%, 95% CI: -2.3, +4.5, p = 0.53. Median AI-carotid was 31.5% before and 28.7% after; median change: -0.5, interquartile range: -9.5, +3.5, p = 0.32. Nineteen patients returned for 6-month recordings; neither blood pressure nor arterial stiffness readings were significantly different from baseline. CONCLUSION: Enhanced external counterpulsation therapy does not significantly alter arterial stiffness. Other than an initial reduction in blood pressure, the sustained clinical benefit seen with this therapy is unlikely to be effected through alterations in arterial wall mechanical properties.

The relationship between androgens and arterial stiffness in older men.

OBJECTIVES: To assess the relationship between endogenous androgen levels and arterial stiffness in older men. DESIGN: A retrospective, cross-sectional study. SETTING: A London hospital-based, clinical research unit for the elderly. PARTICIPANTS: Fifty-five men (mean age+/-standard deviation=71.1+/-8.0). INTERVENTION: Sex hormone-binding globulin (SHBG), testosterone, and dehydroepiandrosterone sulfate (DHEAS) were measured in all subjects who had a stored serum sample drawn the same day as arterial stiffness measures were performed. Free testosterone index (FTI) was calculated ((total testosterone/SHBG) x 100 (%)). The measures of arterial stiffness used were pulse wave velocity (PWV) using the Complior system and systemic arterial compliance (SAC) using the area method. MEASUREMENTS: Relationship between arterial stiffness and serum androgens. RESULTS: : FTI showed a strong positive relationship with SAC (r=0.507, P<.001) and, correspondingly, an inverse relationship with carotid-femoral (C-F) and carotid-radial (C-R) PWV (r=-0.427 and -0.402, respectively, P

Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia.

The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or 'compliance') was measured in 16 men (71+/-9 years, mean+/-S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70+/-7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure ('area method'), and pulse wave velocities (PWVs) were recorded with the 'Complior' system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change+/-S.E.M., -0.26+/-0.09 a.c.u. (arbitrary compliance unit) in the cases versus +0.06+/-0.11 in the controls; P =0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change+/-S.E.M. for aorto-femoral PWV, +0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls; P =0.08). After testosterone suppression, fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l (mean+/-S.D.), total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l; P <0.005 for all. No significant change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.