Patients' evaluation of aftercare following hospitalization for COVID-19: satisfaction and unmet needs.

BACKGROUND: Patient experiences with COVID-19 aftercare remain largely unknown. We evaluated COVID-19 aftercare from a patient perspective one year after hospitalization, assessing satisfaction and its associated factors, and unmet needs. METHODS: The Satisfaction with COVID-19 Aftercare Questionnaire (SCAQ) was developed as part of a multicenter prospective cohort study and administered one year after hospital discharge. The SCAQ assesses (1) patient satisfaction, comprising information provision, rehabilitation, follow-up by hospitals and general practitioners (GPs), the most important aftercare topics, and overall satisfaction, and (2) unmet needs. RESULTS: 487/561 (87%) COVID-19 patients completed the SCAQ, all had been discharged from the hospital between March 2020 and May 2021. Among responders, the median age of patients was 60 (IQR 54-67) years, 338 (69%) were male, and the median length of stay in the hospital was 13 (6-27) days. Patients were least satisfied with information on who could be contacted with questions when health problems arise (59% satisfied or very satisfied). Many patients (75%) received rehabilitation, most frequently community-based (70%). Across the different community-based therapies, ≥ 60% of patients were satisfied with shared-decision making and ≥ 70% with the received therapy; a majority (≥ 79%) indicated a preference for receiving the same therapy again if needed. Regarding follow-up by hospitals, 86% of patients received this follow-up, most frequently visiting a pulmonologist (96%), being generally satisfied with the received aftercare. Aftercare from GPs was received by 39% of patients, with 88% being satisfied with the GP's availability and 79% with referral to appropriate aftercare providers. Patients (> 50%) considered information-related items most important in aftercare. Overall, patients rated their satisfaction with aftercare 8/10 (7-9) points. Those who received medical rehabilitation (versus no rehabilitation, adjusted beta 0.61 [95%CI 0.11 to 1.11], p = 0.02) or aftercare by a hospital medical specialist (1.1 [0.46 to 1.64], p < 0.001) or GP (0.39 [0.053 to 0.72], p = 0.023) reported significantly higher satisfaction than those without such aftercare. Unmet needs were reported by 35% of patients, with lack of information (20%) and lack of additional aftercare and/or involvement of their GP (19%) being the most frequently reported. CONCLUSION: Despite the forced quick development of COVID-19 aftercare, patients were generally satisfied. Follow-up by healthcare professionals and information provision is important to meet patients' aftercare needs.

Acute COVID-19 treatment is not associated with health problems 2 years after hospitalization.

OBJECTIVES: Various mechanisms, such as immune dysregulation, viral reservoir, and auto-immunity, are hypothesized to underlie the pathogenesis of long-term health problems after hospitalization for COVID-19. We aimed to assess the effect of in-hospital COVID-19 treatments on prominent long-term health problems. METHODS: In this prospective multicenter cohort study, we enrolled patients (age ≥18 years) who had been hospitalized for COVID-19 in the Netherlands between July 2020 and October 2021. We retrospectively collected data on in-hospital COVID-19 treatments, including steroid, anti-inflammatory, and antiviral treatments. Patients completed questionnaires on self-reported recovery, dyspnea, fatigue, cognitive failures, and health-related quality of life and performed the 6-minute walk test at the 2-year follow-up visit. RESULTS: Five hundred two patients with COVID-19 were included, all were discharged from the hospital between March 2020 and June 2021. The median age at admission was 60.0 (IQR 53.0-68.0) years and 350 (69.7%) patients were male. At hospital admission, 5/405 (1.2%) of the patients had been vaccinated against SARS-CoV-2. Among all 502 patients, the majority (248 [49.4%]) received steroids only, 57 (11.4%) anti-inflammatory treatment, 78 (15.5%) antiviral treatment, and 119 (23.7%) none during hospitalization. Long-term health problems were common in all groups. We found that in-hospital treatments were not significantly associated with health problems at 2 years after hospital discharge, nor after adjusting for confounders. CONCLUSION: Many patients with COVID-19 suffer from long-term health problems 2 years after hospital discharge. Acute treatment for COVID-19 is not associated with long-term health problems.

Daily patterns of fatigue after subarachnoid haemorrhage: an ecological momentary assessment study.

OBJECTIVE: To examine the daily course of, and factors associated with, momentary fatigue after subarachnoid haemorrhage, and to explore subgroups of patients with distinct diurnal patterns of fatigue. DESIGN: Observational study using ecological momentary assessment. SUBJECTS: A total of 41 participants with subarachnoid haemorrhage. METHODS: Patients with fatigue were included within one year post-onset. Momentary fatigue (scale 1-7) was assessed with repeated measurements (10-11 times/day) during 7 consecutive days. Multilevel-mixed-model analyses and latent-class trajectory modelling were conducted. RESULTS: Mean (standard deviation; SD) age of the group was 53.9 (13.0) years, 56% female, and mean (SD) time post-subarachnoid haemorrhage onset was 9.3 (3.2) months. Mean (SD) momentary fatigue over all days was 3.22 (1.47). Fatigue increased significantly (p < 0.001) over the day, and experiencing more burden of fatigue and day type (working day vs weekend day) were significantly (p < 0.05) associated with higher momentary fatigue. Three subgroups could be distinguished based on diurnal patterns of fatigue. The largest group (n = 17, 41.5%) showed an increasing daily pattern of fatigue. CONCLUSION: Momentary fatigue in patients with subarachnoid haemorrhage increases over the day, and diurnal patterns of fatigue differ between  participants. In addition to conventional measures, momentary measures of fatigue might provide valuable information for physicians to optimize personalized management of fatigue after subarachnoid haemorrhage.

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity.

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs). Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge. Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts. Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study.

BACKGROUND: Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e. a single fatigue score or average PA levels), thereby assuming that fatigue and PA do not fluctuate over time. However, levels of fatigue and PA may not be stable and may interrelate dynamically in daily life. Insight in direct relationships between fatigue and PA in daily life, could add to the development of personalized rehabilitation strategies. Therefore we aimed to examine bidirectional relationships between momentary fatigue and PA in people with SAH. METHODS: People (n = 38) with SAH who suffer from chronic fatigue were included in an observational study using Ecological Momentary Assessment (EMA) and accelerometry. Momentary fatigue was assessed on a scale from 1 to 7 (no to extreme fatigue), assessed with 10-11 prompts per day for 7 consecutive days using EMA with a mobile phone. PA was continuously measured during this 7-day period with a thigh-worn Activ8 accelerometer and expressed as total minutes of standing, walking, running and cycling in a period of 45 min before and after a momentary fatigue prompt. Multilevel mixed model analyses including random effects were conducted. RESULTS: Mean age was 53.2 years (SD = 13.4), 58% female, and mean time post SAH onset was 9.5 months (SD = 2.1). Multilevel analyses with only time effects to predict fatigue and PA revealed that fatigue significantly (p < 0.001) increased over the day and PA significantly (p < 0.001) decreased. In addition, more PA was significantly associated with higher subsequent fatigue (ß = 0.004, p < 0.05) and higher fatigue was significantly associated with less subsequent PA (ß=-0.736, p < 0.05). Moreover, these associations significantly differed between participants (p < 0.001). CONCLUSIONS: By combining EMA measures of fatigue with accelerometer-based PA we found that fatigue and PA are bidirectionally associated. In addition, these associations differ among participants. Given these different bidirectional associations, rehabilitation aimed at reducing fatigue should comprise personalized strategies to improve both fatigue and PA simultaneously, for example by combining exercise therapy with cognitive behavioral and/or energy management therapy.

Early surgery versus conservative treatment in patients with traumatic intracerebral hematoma: a CENTER-TBI study.

PURPOSE: Evidence regarding the effect of surgery in traumatic intracerebral hematoma (t-ICH) is limited and relies on the STITCH(Trauma) trial. This study is aimed at comparing the effectiveness of early surgery to conservative treatment in patients with a t-ICH. METHODS: In a prospective cohort, we included patients with a large t-ICH (< 48 h of injury). Primary outcome was the Glasgow Outcome Scale Extended (GOSE) at 6 months, analyzed with multivariable proportional odds logistic regression. Subgroups included injury severity and isolated vs. non-isolated t-ICH. RESULTS: A total of 367 patients with a large t-ICH were included, of whom 160 received early surgery and 207 received conservative treatment. Patients receiving early surgery were younger (median age 54 vs. 58 years) and more severely injured (median Glasgow Coma Scale 7 vs. 10) compared to those treated conservatively. In the overall cohort, early surgery was not associated with better functional outcome (adjusted odds ratio (AOR) 1.1, (95% CI, 0.6-1.7)) compared to conservative treatment. Early surgery was associated with better outcome for patients with moderate TBI and isolated t-ICH (AOR 1.5 (95% CI, 1.1-2.0); P value for interaction 0.71, and AOR 1.8 (95% CI, 1.3-2.5); P value for interaction 0.004). Conversely, in mild TBI and those with a smaller t-ICH (< 33 cc), conservative treatment was associated with better outcome (AOR 0.6 (95% CI, 0.4-0.9); P value for interaction 0.71, and AOR 0.8 (95% CI, 0.5-1.0); P value for interaction 0.32). CONCLUSIONS: Early surgery in t-ICH might benefit those with moderate TBI and isolated t-ICH, comparable with results of the STITCH(Trauma) trial.

Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort study.

Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014-2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12-26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7-1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0-3.4), n = 200]). Interpretation: We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling. Funding: Hersenstichting Nederland for the Dutch NeuroTraumatology Quality Registry and the European Union Seventh Framework Program.

Cognitive and psychological recovery patterns across different care pathways 12 months after hospitalization for COVID-19: A multicenter cohort study (CO-FLOW).

BACKGROUND: The comparison of recovery patterns for different care pathways following COVID-19 is necessary for optimizing rehabilitation strategies. OBJECTIVES: To evaluate cognitive and psychological outcomes across different care pathways up to 12 months after hospitalization for COVID-19. METHODS: CO-FLOW is an ongoing multicenter prospective cohort study with assessments at 3, 6, and 12 months after hospitalization for COVID-19. The main outcomes are cognitive deficits (Montreal Cognitive Assessment, score <26), cognitive failure (Cognitive Failure Questionnaire, score >43), posttraumatic stress disorder (PTSD; Impact of Event Scale-Revised, score ≥33), and anxiety and depression (Hospital Anxiety and Depression Scale, subscale score ≥11). RESULTS: In total, data from 617 participants were analyzed. Mean age was 59.7 (SD 11.4) years and 188 (31%) were female. Significant recovery occurred within the first 6 months post-discharge (p ≤ 0.001). Cognitive deficits persisted in 21% (101/474), and psychological problems in 15% (74/482) of people at 12 months. Significantly improved cognition scores were reported for people who did not receive rehabilitation ('No-rehab'; 124/617, 20%; mean difference, MD 2.32, 95% CI 1.47 to 3.17; p<0.001), those who received community-based rehabilitation ('Com-rehab'; 327/617, 53%; MD 1.27, 95% CI 0.77 to 1.78; p<0.001), and those who received medical rehabilitation ('Med-rehab'; 86/617, 14%; MD 1.63, 95% CI 0.17 to 3.10; p = 0.029). Med-rehab participants experienced more cognitive failure from 3 to 6 months (MD 4.24, 95% 1.63 to 6.84; p = 0.001). Com-rehab showed recovery for PTSD (MD -2.43, 95% -3.50 to -1.37; p<0.001), anxiety (MD -0.67, 95% -1.02 to -0.32; p<0.001), and depression (MD -0.60, 95% -0.96 to -0.25; p<0.001), but symptoms persisted at 12 months. CONCLUSIONS: Survivors of COVID-19 showed cognitive and psychological recovery, especially within the first 6 months after hospitalization. Most persistent problems were related to cognitive functioning at 12 months. Recovery differed rehabilitation settings. Additional cognitive or psychological support might be warranted in people who medical or community-based rehabilitation.

Physical fitness and its association with fatigue in patients with low-grade glioma.

PURPOSE: To evaluate physical fitness and its association with fatigue in patients with low grade glioma (LGG). METHODS: Cross-sectional study. Muscle strength was measured with a digital dynamometer, cardiorespiratory fitness (peak oxygen uptake (VO2peak), maximal workload (MWL)) by cardiopulmonary-exercise-testing, and fatigue by using the Multidimensional Fatigue Inventory. RESULTS: Thirty patients were included, mean age of 44.1 (SD11.2) years, and 67% were men, 31.2 (SD18) months post-diagnosis. Muscle strength (p < 0.01), and cardiorespiratory fitness (VO2peak, MWL) (p < 0.01) were significantly decreased compared to predicted values based on age and gender. Thirty percent of the patients experienced severe physical fatigue, and severe mental fatigue was reported in 57% of the patients. Cardiorespiratory fitness showed weak to moderate (r - 0.46 to r - 0.52) but significant (p < 0.01) correlations with physical fatigue, not with mental and general fatigue. Muscle strength was not associated with fatigue. A lower VO2peak was independently associated with a higher level of physical fatigue, adjusted for Karnofsky Performance Status (R2 0.40). CONCLUSIONS: Physical fitness (muscle strength, cardiorespiratory fitness) is reduced in patients with LLG, and a lower level of cardiorespiratory fitness (VO2peak) is independently associated with a higher level of experienced physical fatigue. Trials to explore the benefit of exercise programs to improve cardiorespiratory fitness and, consequently, fatigue are warranted.Implications for rehabilitationPhysical fitness (muscle strength and cardiorespiratory fitness) is reduced in patients with low-grade glioma.Patients with low-grade glioma should be screened for fatigue with the multidimensional fatigue inventory, to differentiate between mental and physical fatigue.Patients with low-grade glioma with severe physical fatigue should be screened for reduced physical fitness, especially cardiorespiratory fitness by objective cardiopulmonary-exercise-testing.Rehabilitation exercise programs to improve cardiorespiratory fitness and, consequently, (physical) fatigue could be warranted in patients with low-grade glioma.

Symptoms persisting after hospitalisation for COVID-19: 12 months interim results of the CO-FLOW study.

Introduction: A large proportion of patients experience a wide range of sequelae after acute COVID-19, especially after severe illness. The long-term health sequelae need to be assessed. Our objective was to longitudinally assess persistence of symptoms and clusters of symptoms up to 12 months after hospitalisation for COVID-19 and to assess determinants of the main persistent symptoms. Methods: In this multicenter prospective cohort study patients with COVID-19 are followed up for 2 years with measurements at 3, 6, 12 and 24 months after hospital discharge. Here, we present interim results regarding persistent symptoms up to 12 months. Results: We included 492 patients; mean±sd age was 60.2±10.7 years, 335 (68.1%) were males, median length of hospital stay was 11 (6.0-27.0) days. At 3 months after discharge 97.0% of the patients had at least one persisting symptom, this declined to 95.5% and 92.0% at 6 and 12 months, respectively (p=0.010). Muscle weakness, exertional dyspnoea, fatigue, and memory and concentration problems were the most prevalent symptoms with rates over 50% during follow-up. Over time, muscle weakness, hair loss and exertional dyspnoea decreased significantly (p<0.001), while other symptoms such as fatigue, concentration and memory problems, anosmia and ageusia persisted. Symptoms from the physical and respiratory cluster declined significantly over time, in contrast to the fatigue and cognitive symptom clusters. Conclusion: The majority of patients experienced COVID-19 sequelae up to 12 months after severe infection. Whereas physical and respiratory symptoms showed slow gradual decline, fatigue and cognitive symptoms did not evidently resolve over time.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Physical recovery across care pathways up to 12 months after hospitalization for COVID-19: A multicenter prospective cohort study (CO-FLOW).

Backgroud: The sudden COVID-19 pandemic forced quick development of care pathways for patients with different needs. Trajectories of physical recovery in hospitalized patients for COVID-19 following different care pathways are unknown. We aimed to assess trajectories of physical recovery and levels of physical function reached within the different care pathways. Additionally, we assessed differences in physical function across care pathways at follow-up visits. Methods: This multicenter prospective cohort study of adults who had been hospitalized for COVID-19 was performed in 10 centers, including 7 hospitals (1 academic and 6 regional hospitals) and 3 rehabilitation centers (1 medical rehabilitation center and 2 skilled nursing facilities), located in the Netherlands. Study visits were performed at 3, 6, and 12 months post-hospital discharge and included assessment of cardiorespiratory fitness (6 min walk test [6MWT], 1 min sit-to-stand test [1MSTST]), muscle strength (maximum handgrip strength [HGS]) and mobility (de Morton Mobility Index [DEMMI]). Findings: We report findings for 582 patients who had been discharged from hospital between March 24, 2020 and June 17, 2021. Patients had a median age of 60·0 years, 68·9% (401/582) were male, 94·6% (561/582) had received oxygen therapy, and 35·2% (205/582) mechanical ventilation. We followed patients across four different rehabilitation settings: no rehabilitation (No-rehab, 19·6% [114/582]), community-based rehabilitation (Com-rehab, 54·1% [315/582]), medical rehabilitation (Med-rehab, 13·7% [80/582]), and rehabilitation in a skilled nursing facility (SNF-rehab, 12·5% [73/582]). Overall, outcomes in 6MWT (14·9 meters [95% CI 7·4 to 22·4]), 1MSTST (2·2 repetitions [1·5 to 2·8]), and HGS (3·5 kg [2·9 to 4·0]) improved significantly (p<0·001) from 3 to 6 months and only HGS from 6 to 12 months (2·5 kg [1·8 to 3·1]; p<0·001). DEMMI scores did not significantly improve over time. At 3 months, percentage of normative values reached in 1MSTST differed significantly (p<0.001) across care pathways, with largest impairments in Med- and SNF-rehab groups. At 12 months these differences were no longer significant, reaching, overall, 90·5% on 6MWD, 75·4% on 1MSTST, and 106·9% on HGS. Interpretation: Overall, physical function improved after hospitalization for COVID-19, with largest improvement within 6 months post-discharge. Patients with rehabilitation after hospital discharge improved in more than one component of physical function, whereas patients without rehabilitation improved solely in muscle strength. Patients who received rehabilitation, and particularly patients with Med- and SNF-rehab, had more severe impairment in physical function at 3 months, but reached equal levels at 12 months compared to patients without follow-up treatment. Our findings indicate the importance of rehabilitation. Funding: ZonMw, Rijndam Rehabilitation, Laurens (The Netherlands).

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021.

Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery. Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study.

BACKGROUND: Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. METHODS: We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). FINDINGS: Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77-1·09). INTERPRETATION: Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. FUNDING: The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).

HIGH-VOLUME AND HIGH-INTENSITY FUNCTIONAL TRAINING IN PATIENTS WITH MULTIPLE SCLEROSIS: A PILOT STUDY ON FEASIBILITY AND FUNCTIONAL CAPACITY.

Objective: To evaluate the feasibility of a high-volume and high-intensity functional training programme in patients with multiple sclerosis (MS), and to explore whether functional capacity improves. A further objective was to explore changes in muscle strength and aerobic capacity. Methods: This pilot study comprised a 12-week intervention, with an 8-week follow-up period. The intervention consisted of 3 weekly 3-h training sessions, comprising functional resistance-, endurance-, and skills training. Feasibility (questionnaire), functional capacity (Timed Up and Go Test, 10-Meter Walk Test, and 6-Minute Walk Test), aerobic capacity (cardiopulmonary exercise test) and muscle strength (1 repetition maximum (RM) leg press) were evaluated. Results: Seven patients completed the study. Patients attended a mean of 93% of the training sessions. One adverse event was reported, which was not related to the training programme. Patients scored positive or very positive on 86% of the feasibility aspects and scored an overall grade of 8.9 on a scale of 1-10 regarding satisfaction with the training programme. Functional capacity, aerobic capacity, and muscle strength seemed to be improved after the training programme, but the improvements were not always sustained. Conclusion: This new high-volume and high-intensity functional training programme appeared to be feasible in patients with MS, and may improve their functional capacity, aerobic capacity and muscle strength. A large-scale controlled trial over a longer period of time is required to evaluate the added value of the training programme.

Fatigue is Associated with Reduced Participation and Health-Related Quality of Life Five Years After Perimesencephalic Subarachnoid Haemorrhage: A Multicentre Cross-Sectional Study.

OBJECTIVE: To determine whether fatigue is associated with participation and health-related quality of life 5 years after perimesencephalic subarachnoid haemorrhage. DESIGN: Multicentre cross-sectional study. SUBJECTS: Forty-six patients with perimesencephalic subarachnoid haemorrhage. METHODS: Fatigue was assessed with the Fatigue Severity Scale, participation (frequency, restrictions, satisfaction) with the Utrecht Scale for Evaluation of Rehabilitation-Participation, healthrelated quality of life with the Stroke-Specific Quality of Life Scale-12, symptoms of depression and anxiety with the Hospital Anxiety and Depression Scale, and coping with the Coping Inventory for Stressful Situations. RESULTS: A total of 46 patients were included (63% men, mean age 50.4 ± 9.4 years), with a mean time of 4.7 ± 1.6 years after perimesencephalic subarachnoid haemorrhage onset. Fatigued patients (33%) had worse participation (p < 0.01) and health-related quality of life (p < 0.001) than non-fatigued patients, and more often had hypertension, depression, anxiety and emotion-oriented coping (p < 0.05). Fatigue severity was inversely and independently (p < 0.005) associated with participation frequency (B = -3.62), satisfaction (B = -4.54), having restrictions (odds ratio = 2.48, 95% confidence interval 1.079-5.685), and health-related quality of life (B = -0.19), adjusted for depression, anxiety, and/or hypertension. CONCLUSION: Five years after perimesencephalic subarachnoid haemorrhage, one-third of patients still reported fatigue, which was associated with worse participation and health-related quality of life. Future studies should examine whether these patients may benefit from rehabilitation aimed at fatigue.

A delphi procedure on rehabilitation outcome for patients with moderate to severe traumatic brain injury; first phase of the Neurotraumatology Quality Registry (NET-QURE).

OBJECTIVE: To select a set of rehabilitation outcome instruments for a national Neurotrauma Quality Registry (Net-QuRe) among professionals involved in the care of patients with traumatic brain injury. DESIGN: A 3-round online Delphi procedure. SUBJECTS: Eighty professionals from multiple disciplines working in 1 of the 8 participating rehabilitation centres were invited to participate. The response rate varied from 70% to 76% per round. METHODS: For the Delphi procedure, multiple outcome categories were defined based on the International Classification of Functioning, Disability and Health (ICF) with concomitant measurement instruments. For each category we strived for consensus on one instrument of at least 75%. RESULTS: After the first round, consensus was reached for the category subjective cognitive functioning. After the second round for quality of life, pain, general functioning, anxiety and depression, general psychological functioning, communication (impairment), and personal factors. Finally, after the third round, consensus was reached for activities of daily living, participation, self-awareness, and aphasia. No consensus was reached for the categories motor function, cognitive function, comorbidity, fatigue, and employment status. CONCLUSION: Consensus was reached in 12 out of 17 outcome categories. A Delphi procedure seems to be a feasible method to collectively select measurement instruments for a multicentre study.

The relationship between mental fatigue, cognitive functioning, and employment status in patients with low-grade glioma: a cross-sectional single-center study.

PURPOSE: To evaluate fatigue and cognitive functioning in patients with low-grade glioma and to assess whether cognitive functioning and employment status differ between patients with severe and non-severe mental fatigue. METHODS: Cross-sectional study. Fatigue was measured with the multidimensional fatigue inventory, objective cognitive functioning with a neuropsychological test battery, and mood with the Center for Epidemiological Studies Depression Scale. RESULTS: Thirty-one patients, mean age 44 ± 11, mean time post-diagnosis 2.5 ± 1.4 years, participated. Severe mental fatigue was present in 55% and depression in 36% of the patients. Attention deficits were observed in 75% (Stroop's test), memory deficits in 36% (Rey Auditory Verbal Learning Test), and executive functioning deficits in 42% (Stroop's test). Severe mental fatigue patients demonstrated significantly worse scores on Stroop's test-Card-II (p = 0.043), Trail Making Test-B (p = 0.014), Trail Making Test-B/A (p = 0.014), and Digit-Span (p = 0.046), compared to non-severe mental fatigue patients. Severe mental fatigue patients worked significantly less hours per week (p = 0.013) and had more changes in their employment status (p = 0.009) after diagnosis. CONCLUSIONS: Patients with low grade glioma show high rates of fatigue, especially in the mental domain, which might be associated with deficits in cognitive functioning and changes in employment status.Implications for rehabilitationThe majority of patients with low grade glioma suffers from severe mental fatigue and has deficits in cognitive functioning, which may affect employment status.Patients with low grade glioma should be screened for fatigue with the multidimensional fatigue inventory, to differentiate between mental and physical fatigue.Patients with low grade glioma with severe mental fatigue should be screened for problems in cognitive functioning with an objective neuropsychological test battery.Cognitive and vocational rehabilitation programs should aim at coping with severe mental fatigue and attention deficits in patients with low grade glioma.

Persistent Health Problems beyond Pulmonary Recovery up to 6 Months after Hospitalization for COVID-19: A Longitudinal Study of Respiratory, Physical, and Psychological Outcomes.

Rationale: Data on longitudinal recovery after hospitalization for coronavirus disease (COVID-19) currently remain scarce, just as outcomes beyond 3 months of follow-up do. Objectives: To evaluate the sequelae up to 6 months after hospitalization for COVID-19 by considering 1) recovery as it relates to pulmonary function, radiological abnormalities, physical and mental health status, and health-related quality of life (HR-QoL) and 2) the predictors of the most clinically relevant sequelae. Methods: Patients were evaluated at 6 weeks, 3 months, and 6 months after hospitalization by using pulmonary function testing, radiological evaluation, and online questionnaires on the physical and mental health status and HR-QoL. Outcomes were analyzed using repeated-measurement analyses. Results: Ninety-two patients were included (mean age, 58.2 ± 12.3 yr; 58 [63.0%] men). The estimated percentage of patients with impaired forced vital capacity improved from 25% at 6 weeks to 11% at 6 months; for impaired diffusion capacity, this percentage improved from 63% to 46%. Radiologically, ground-glass opacity decreased but fibrosis persisted. The majority of patients (89.1%) still reported one or more symptoms 6 months after discharge. Fatigue decreased significantly over time (P = 0.006). Nonetheless, fatigue remained in 51% of the patients at 6 months. HR-QoL (nearly) normalized in most domains at 6 months, except for physical role functioning, with persistent fatigue and the length of hospitalization being the most important predictors. Conclusions: During the first 6 months after hospitalization for COVID-19, most patients demonstrated continuing recovery across all health domains, but persistent sequelae were frequent. Fatigue was the most frequent residual and persistent symptom up to 6 months after hospitalization, importantly impacting HR-QoL.

CO-FLOW: COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: study protocol of a multicenter prospective cohort study following patients 2 years after hospital discharge.

BACKGROUND: First studies indicate that up to 6 months after hospital discharge, coronavirus disease 2019 (COVID-19) causes severe physical, cognitive, and psychological impairments, which may affect participation and health-related quality of life (HRQoL). After hospitalization for COVID-19, a number of patients are referred to medical rehabilitation centers or skilled nursing facilities for further treatment, while others go home with or without aftercare. The aftercare paths include 1] community-based rehabilitation; 2] in- and outpatient medical rehabilitation; 3] inpatient rehabilitation in skilled nursing facilities; and 4] sheltered care (inpatient). These aftercare paths and the trajectories of recovery after COVID-19 urgently need long-term in-depth evaluation to optimize and personalize treatment. CO-FLOW aims, by following the outcomes and aftercare paths of all COVID-19 patients after hospital discharge, to systematically study over a 2-year period: 1] trajectories of physical, cognitive, and psychological recovery; 2] patient flows, healthcare utilization, patient satisfaction with aftercare, and barriers/facilitators regarding aftercare as experienced by healthcare professionals; 3] effects of physical, cognitive, and psychological outcomes on participation and HRQoL; and 4] predictors for long-term recovery, health care utilization, and patient satisfaction with aftercare. METHODS: CO-FLOW is a multicenter prospective cohort study in the mid-west of the Netherlands with a 2-year follow-up period. Measurements comprise non-invasive clinical tests and patient reported outcome measures from a combined rehabilitation, pulmonary, and intensive care perspective. Measurements are performed at 3, 6, 12, and 24 months after hospital discharge and, if applicable, at rehabilitation discharge. CO-FLOW aims to include at least 500 patients who survived hospitalization for COVID-19, aged ≥18 years. DISCUSSION: CO-FLOW will provide in-depth knowledge on the long-term sequelae of COVID-19 and the quality of current aftercare paths for patients who survived hospitalization. This knowledge is a prerequisite to facilitate the right care in the right place for COVID-19 and comparable future infectious diseases. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), https://www.trialregister.nl . Registered: 12-06-2020, CO-FLOW trialregister no. NL8710.