Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients.

BACKGROUND: Ferritin is an established biomarker in the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH), which is diagnosed by the HLH-2004 criteria. Among these criteria, detection of hemophagocytosis through invasive procedures may delay early life saving treatment. Our aim was to investigate the value of hemophagocytosis in diagnosing HLH in critically ill patients. METHODS: In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 µg/L) and underwent bone marrow biopsy during their ICU course. RESULTS: Two hundred fifty-two patients were included, of whom 31 (12.3%) showed hemophagocytosis. In multivariable logistic regression analysis, maximum ferritin was independently associated with hemophagocytosis. By removing hemophagocytosis from HLH-2004 criteria and HScore, prediction accuracy for HLH diagnosis was only marginally decreased compared to the original scores. CONCLUSIONS: Our results strengthen the diagnostic value of ferritin and underline the importance of considering HLH diagnosis in patients with high ferritin but only four fulfilled HLH-2004 criteria, when hemophagocytosis was not assessed or not detectable. Proof of hemophagocytosis is not required for a reliable HLH diagnosis.

The role of habitual learning in premotor attention allocation.

Dual-task studies have demonstrated that goal-directed actions are typically preceded by a premotor shift of visual attention toward the movement goal location. This finding is often taken as evidence for an obligatory coupling between attention and motor preparation. Here, we examined whether this coupling entails a habitual component relating to an expectation of spatial congruence between visual and motor targets. In two experiments, participants had to identify a visual discrimination target (DT) while preparing variably delayed pointing movements to a motor target (MT). To induce distinct expectations regarding the DT position, different groups of participants performed a training phase in which the DT either always appeared at MT, opposite to MT, or at an unpredictable position. In a subsequent test phase, the DT position was randomized to assess the impact of learned expectancy on premotor attention allocation. Although we applied individually determined DT presentation times in the test phase of Experiment 1, a fixed DT presentation time was used in Experiment 2. Both experiments yielded evidence for attentional enhancement at the expected DT position. Although interpretability of this effect was limited in Experiment 1 because of between-group differences in DT presentation time, results of Experiment 2 were much clearer. Specifically, a marked discrimination benefit was observed at the position opposite to MT in participants anticipating the DT at this position, whereas no statistically significant benefit was found at MT. Crucially, this was observed at short movement delays, demonstrating that expectation of spatial incongruence between visual and motor targets allows for decoupling of attentional resources from ongoing motor preparation. Based on our findings, we suggest that premotor attention shifts entail a considerable habitual component rather than being the sole result of motor programming.

[Clinical examination of spatial neglect and other disorders of spatial cognition]. / Klinische Untersuchung des unilateralen Neglects und weiterer Störungen der Raumkognition.

Neglect occurring after stroke, neoplasms or degenerative processes can lead to considerable disability in everyday life as can other disorders of spatial orientation. Therefore, a dedicated examination and early diagnostic classification are obligatory. Behavioral tests are helpful in this respect, enabling the clinician to obtain an initial overview of the existing deficits even at the patient's bedside. The clinical (bedside) examination of spatial neglect as well as the corresponding differential diagnostic procedure for the clarification of (possibly additionally or exclusively existing) hemianopia and extinction, as well as the examination of disorders of visuospatial perception, visuoconstructive disorders, topographic disorders, Bálint's syndrome, simultanagnosia, and optic ataxia are presented. The presentation is based on the newly revised (year 2023) guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) on this subject area.

Temporal order judgments and presaccadic shifts of attention: What can prior entry teach us about the premotor theory?

A temporal order judgment (TOJ) 2-alternative forced choice design was used to examine presaccadic shifts of attention. Prior work on the premotor theory of attention (PTA) has predominantly focused on single-target discrimination tasks as a tool to measure accuracy and shifts of attention. It is important to demonstrate that the PTA is effective across attentional tasks that have been shown to be reliable in other contexts. Therefore, it was decided to use a perceptual task that probes multiple locations simultaneously and can equally be used to examine spatial spread of attention in more detail. In typical TOJ studies, prior entry is the metric used to measure an attentional effect. Prior entry is the biasing of temporal perception toward an attentionally cued location. This generally manifests as observers processing events at the cued location more rapidly, altering their perspective of temporal order. Participants were required to prepare saccades toward one of four targets, two of which would light up either synchronously or sequentially after a GO signal but before saccadic execution. Results demonstrated that in conditions with critical stimulus onset asynchronies, saccade preparation had a significant effect on performance. Prior entry effects were observed at saccade congruent locations with probes at these locations being typically perceived earlier than probes presented at a neutral location. These effects were not observed in control trials without a saccade. A further spatial effect was demonstrated for the attentional modulation, suggesting that this effect is restricted predominantly to horizontal configurations. Overall, results demonstrated that presaccadic attention is effective at eliciting a prior entry effect in TOJ designs and that such effects are more pronounced when the probes are distributed across the two lateral hemifields.

Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial.

Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial. Patients received a test dose of 10-mg/kg sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later and 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication. No drug-related serious adverse events were observed. Seven of 10 patients with cold agglutinin disease responded with a hemoglobin increase >2 g/dL. Sutimlimab rapidly increased hemoglobin levels by a median of 1.6 g/dL within the first week, and by a median of 3.9 g/dL (interquartile range, 1.3-4.5 g/dL; 95% confidence interval, 2.1-4.5) within 6 weeks (P = .005). Sutimlimab rapidly abrogated extravascular hemolysis, normalizing bilirubin levels within 24 hours in most patients and normalizing haptoglobin levels in 4 patients within 1 week. Hemolytic anemia recurred when drug levels were cleared from the circulation 3 to 4 weeks after the last dose of sutimlimab. Reexposure to sutimlimab in a named patient program recapitulated the control of hemolytic anemia. All 6 previously transfused patients became transfusion-free during treatment. Sutimlimab was safe, well tolerated, and rapidly stopped C1s complement-mediated hemolysis in patients with cold agglutinin disease, significantly increasing hemoglobin levels and precluding the need for transfusions. This trial was registered at www.clinicaltrials.gov as #NCT02502903.

Trait mindfulness is primarily associated with depression and not with fatigue in multiple sclerosis (MS): implications for mindfulness-based interventions.

OBJECTIVES: Persons with MS (PwMS) often display symptoms of depression and fatigue. Mindfulness-based interventions are known to counteract these symptoms. However, to-date the exact relations between trait mindfulness, depression and fatigue remain to be examined. Fatigue is generally regarded as a symptom immanent to the disease and as a direct neurobiological consequence of increased cytokine levels and cortical atrophy. In depression on the other hand, psychosocial factors in the context of adaptation difficulties are probably of higher relevance. Hence, one may argue that mindfulness, as a trait that promotes successful adaption, may show a strong negative association with depression and a relatively minor negative association with fatigue in PwMS. METHODS: In the current study, the association between self-reported trait mindfulness, fatigue and depression was examined in a sample of 69 PwMS. RESULTS: Trait mindfulness showed highly significant negative correlations with both, depression and fatigue. Mediation analyses however, revealed that depression mediated the relation between mindfulness and fatigue. CONCLUSION: It may be concluded that in PwMS, trait mindfulness shows a genuine negative association with depression, but that it is only secondarily associated with fatigue. Implications for mindfulness-based interventions in MS are discussed. Based on the results of the current study, it may be feasible to promote the acceptance of default fatigue symptoms, instead of an actual reduction of fatigue symptoms.

Mindfulness training during brief periods of hospitalization in multiple sclerosis (MS): beneficial alterations in fatigue and the mediating role of depression.

OBJECTIVES: Persons with MS (PwMS) are frequently affected by fatigue and depression. Mindfulness-based interventions may reduce these symptoms in PwMS and consequently their application has been extended to various settings. Only few efforts have been made to explore effects of short-term mindfulness training during brief periods of hospitalization. In the current study, the feasibility and potential effects of short-term mindfulness training on depression, fatigue, rumination and cognition were explored in PwMS in an acute-care hospital setting. Based on previous work, it was further examined whether the relation between trait mindfulness and fatigue prior to and following the intervention was mediated by depression and whether a mediation effect was also observable throughout the intervention. METHODS: A short-term mindfulness training protocol was developed, tailored to the requirements of the acute-care setting. Subsequently, 30 PwMS were recruited sequentially and received mindfulness training during the routine clinical process (median duration in hospital: eight days, number of sessions: four). Participants completed relevant self-report measures (depression, fatigue, rumination) and a neuropsychological assessment before and after training. RESULTS: Participants reported significantly increased trait mindfulness and decreased depression and fatigue following the intervention. Respective change scores were highly correlated so that increased trait mindfulness was associated with decreased symptoms. In the rumination domain, patients reported a tendency for an increased adaptive ability to engage in distractive behavior during arising negative mood. Other measures of trait rumination and cognition remained relatively stable. Results of the mediation analyses indicated that depression mediated the negative relationship between trait mindfulness and fatigue symptoms at pre and post assessments. With regards to the change scores, an association between mindfulness and cognitive fatigue ceased to be significant when depression was controlled, albeit in this case, the mediation effect did not reach significance. CONCLUSION: Results of the current study indicate that short-term mindfulness training during brief periods of hospitalization may be beneficial for PwMS. They further complement previous work by identifying depression as a potential mediator of the antagonistic relationship between mindfulness and fatigue. Based on the current exploratory study, future trials are warranted to address this mechanism of mindfulness training in more detail.

Living with global amnesia: self-established compensation strategies of a patient with severe memory impairment - a narrative report.

We report the case of C.H., a 48-year-old patient with global amnesia caused by herpes simplex encephalitis at the age of 20 and subsequent extensive bilateral temporal lobe lesions. Neuropsychological examinations performed at various intervals found persistent dense explicit memory impairment and limited vocabulary, yet intact procedural memory. Despite these limitations, C.H. self-developed and acquired a variety of effective strategies. As a result, C.H. achieved a high level of autonomy in everyday life. Her remarkable case is an encouraging and helpful example for successful implementation of creative methods and procedures to compensate and alleviate cognitive limitation, even if extensive.

Hyperferritinemia in Critically Ill Patients.

OBJECTIVE: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. DESIGN: Retrospective observational study. SETTING: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. PATIENTS: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949-0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384-1.665 per log µg/L]; p < 0.001). CONCLUSIONS: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

Treatment and Mortality of Hemophagocytic Lymphohistiocytosis in Adult Critically Ill Patients: A Systematic Review With Pooled Analysis.

OBJECTIVES: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients. DATA SOURCES: MEDLINE database (PubMed) at October 20, 2019. STUDY SELECTION: Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU. DATA EXTRACTION: Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination. DATA SYNTHESIS: In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337-0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702-15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors. CONCLUSIONS: Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.

The Progressive Supranuclear Palsy Clinical Deficits Scale.

BACKGROUND: There is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes. OBJECTIVE: To develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes. METHODS: The Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts). RESULTS: Cognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P < 0.001). Individual Progressive Supranuclear Palsy Clinical Deficits Scale items correlated well with similar constructs in existing scales. Internal consistency (Cronbach's alpha: 0.75), inter-rater reliability (0.96), and test-retest stability (0.99) were acceptable. The PSP-CDS showed significant 12-month change (baseline, 8.6 ± 3.6; follow-up: 10.8 ± 3.6; annualized difference: 3.4 ± 3.4; n = 49; P < 0.0001). Sample sizes required per arm for a two-arm, 1-year follow-up therapeutic trial to detect 50% change in Progressive Supranuclear Palsy Clinical Deficits Scale progression was estimated to be 65 (two-sided, two-sample t test). CONCLUSION: The Progressive Supranuclear Palsy Clinical Deficits Scale is a rapidly completed, clinimetrically sound scale for clinical care and research involving PSP. © 2020 International Parkinson and Movement Disorder Society.

Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. METHODS: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 µg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. RESULTS: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 µg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p <  0.001] were significantly associated with in-hospital mortality. CONCLUSIONS: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. CLINICAL TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

Grasping and perception are both affected by irrelevant information and secondary tasks: new evidence from the Garner paradigm.

In their Perception-Action Model (PAM), Goodale and Milner (1992) proposed functionally independent and encapsulated processing of visual information for action and perception. In this context, they postulated that visual input for action is processed in an automatized and analytic manner, which renders visuomotor behaviour immune to perceptual interferences or multitasking costs due to sharing of cognitive resources. Here, we investigate the well-known Garner Interference effect under dual- and single-task conditions in its classic perceptual form as well as in grasping. Garner Interference arises when stimuli are classified along a relevant dimension (e.g., their length), while another irrelevant dimension (e.g., their width) has to be ignored. In the present study, participants were presented with differently sized rectangular objects and either grasped them or classified them as long or short via button presses. We found classical Garner Interference effects in perception as expressed in prolonged reaction times when variations occurred also in the irrelevant object dimension. While reaction times during grasping were not susceptible to Garner Interference, effects were observed in a number of measures that reflect grasping accuracy (i.e., poorer adjustment of grip aperture to object size, prolonged adjustment times, and increased variability of the maximum hand opening when irrelevant object dimensions were varied). In addition, multitasking costs occurred in both perception and action tasks. Thus, our findings challenge the assumption of automaticity in visuomotor behaviour as proposed by the PAM.

Transient naming deficits associated with insular lesions in a patient with encephalitis.

We describe a patient with acute herpes simplex encephalitis with left-hemispheric hippocampal, parahippocampal and insular lesions. Although prototypic language areas were unaffected, the patient suffered from an inability to name objects or animals displayed on pictures. This deficit was transient and gradually disappeared 8 weeks after the initial diagnosis. Our findings are in line with a previous report showing similar deficits in a patient with a comparable lesion pattern and support the hypothesis that left insular lesions can produce severe naming deficits. Using FDG-PET we ruled out that functional deactivation in classical language areas account for the observed naming deficits.

The visual guidance of action is not insulated from cognitive interference: A multitasking study on obstacle-avoidance and bisection.

The Perception-Action Model (PAM) considers the visual system to be divided into two streams defined by their specific functions, a ventral stream for vision and a dorsal stream for action. In this study we investigated two behavioral paradigms which according to PAM represent the two contrasting functions of the ventral and dorsal stream, namely bisection and obstacle-avoidance, respectively. It is an assumption of PAM that while ventral stream processing is ultimately linked with processing in other cognitive systems, dorsal stream processing is insulated from cognition. Accordingly it can be expected that a secondary task will interfere with bisection but not with obstacle-avoidance. We tested this prediction using a rapid serial visual presentation task as our secondary task (RSVP). Contrary to expectations we found significant interference for both bisection and obstacle-avoidance. Our findings suggest that dorsal-stream processing is not insulated from cognitive processes.

Cryoballoon vs. open irrigated radiofrequency ablation for paroxysmal atrial fibrillation: long-term FreezeAF outcomes.

BACKGROUND: Effective treatment of paroxysmal atrial fibrillation (AF) is essential for reducing the risk of stroke and heart failure. Cryoballoon (CB) ablation has been developed as an alternative to the use of radiofrequency (RF) energy for electrical isolation of the pulmonary veins. Herein, we provide long-term data regarding the efficacy of CB ablation in comparison to RF. METHODS: FreezeAF was a randomised non-inferiority study comparing CB ablation with RF ablation for the treatment of patients with drug-refractory paroxysmal AF. Procedural success for the long-term follow-up (30 months) was defined as freedom from AF with an absence of persistent complications. RESULTS: Of the 315 patients that were randomised and received catheter ablation, 292 (92.7%) completed the 30-month follow-up (147 in the RF group and 145 in the CB group). The baseline characteristics of the RF and CB groups were similar. Single-procedure success was achieved by 40% of patients in the RF group and 42% of the CB group (p < 0.001 for non-inferiority). When including re-do procedures in the analysis, the multiple procedure success rate was 72% in the RF group and 76% in the CB group. CONCLUSION: The data provide long-term evidence that CB ablation is non-inferior to RF ablation, with high proportions of patients reporting freedom from AF 30 months after the index procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00774566 ; first registered October 16, 2008; first patient included October 20, 2008.

Increased prevalence of posttraumatic stress disorder in patients after transient ischemic attack.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) involves temporary neurological symptoms but leaves a patient symptom-free. Patients are faced with an increased risk for future stroke, and the manifestation of the TIA itself might be experienced as traumatizing. We aimed to investigate the prevalence of posttraumatic stress disorder (PTSD) after TIA and its relation to patients' psychosocial outcome. METHODS: Patients with TIA were prospectively studied, and 3 months after the diagnosis, PTSD, anxiety, depression, quality of life, coping strategies, and medical knowledge were assessed via self-rating instruments. RESULTS: Of 211 patients with TIA, data of 108 patients were complete and only those are reported. Thirty-two (29.6%) patients were classified as having PTSD. This rate is 10× as high as in the general German population. Patients with TIA with PTSD were more likely to show signs of anxiety and depression. PTSD was associated with the use of maladaptive coping strategies, subjectively rated high stroke risk, as well as with younger age. Finally, PTSD and anxiety were associated with decreased mental quality of life. CONCLUSIONS: The experience of TIA increases the risk for PTSD and associated anxiety, depression, and reduced mental quality of life. Because a maladaptive coping style and a subjectively overestimated stroke risk seem to play a crucial role in this adverse progression, the training of adaptive coping strategies and cautious briefing about the realistic stroke risk associated with TIA might be a promising approach. Despite the great loss of patients to follow-up, the results indicate that PTSD after TIA requires increased attention.

Quality of life is associated with physical activity and fitness in cystic fibrosis.

BACKGROUND: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess - among other domains - daily functioning from a patient's perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF. METHODS: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power. RESULTS: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55). CONCLUSIONS: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00231686.

The Subarachnoid Hemorrhage International Trialists (SAHIT) Repository: advancing clinical research in subarachnoid hemorrhage.

Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15 years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuroimaging, and laboratory results and various outcome measures. We have compiled the largest known dataset of patients with SAH. The SAHIT repository may be an important resource for advancing clinical research in SAH and will benefit from contributions of additional datasets.

Diagnosis of spontaneous cervical artery dissection may be associated with increased prevalence of posttraumatic stress disorder.

BACKGROUND: Receiving information that one has a dissected cervical artery, which can cause a stroke at any time, is obviously traumatic, but details about the psychiatric and psychosocial sequelae are not known. We investigated the prevalence of and risk factors for posttraumatic stress disorder (PTSD) in patients with spontaneous cervical artery dissection (CD) and the impact of PTSD on their psychosocial functioning. METHODS: Patients admitted because of CD between 2006 and 2010 were retrospectively examined using a diagnostic PTSD measure (Posttraumatic Diagnostic Scale). Patients between 2011 and 2012 were examined prospectively. To identify potential predictors for PTSD, we examined all patients' stress coping strategies (brief COPE inventory), anxiety and depression (Hospital Anxiety and Depression Scale), impairment by preventive medication, time since diagnosis and their neurologic (modified Rankin Scale) and cognitive status. To identify the psychosocial impact of PTSD, we examined quality of life (Short-Form 36). RESULTS: Data of 47 retrospectively contacted patients and 15 prospectively examined patients were included. Twenty-eight patients (45.2%) met the diagnostic criteria for PTSD. A significantly reduced health-related quality of life (HRQoL) was found in 27 patients (43.5%) for mental health and in 8 patients (12.9%) for physical health. Results of logistic regression analysis revealed that the use of maladaptive coping strategies was predictive of the disorder (P < .0001). Age, sex, mRS score, impairment caused by medication, and time since diagnosis were not predictive for PTSD. The presence of PTSD itself was the only significant predictor for reduced mental HRQol (P = .0004). Age, sex, mRS score, impairment caused by medication, and total Hospital Anxiety and Depression Scale score were not predictive for reduced mental HRQoL. CONCLUSIONS: PTSD seems to occur frequently in patients with CD and is associated with reduced mental HRQoL. Because the presence of a maladaptive coping style is correlated with PTSD, teaching patients better coping skills might be helpful.