Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Effect of Physical Exercise on MRI-Assessed Brain Perfusion in Chemotherapy-Treated Breast Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking. PURPOSE: Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes relate to memory function. STUDY TYPE: Prospective. POPULATION: A total of 181 chemotherapy-treated stage I-III breast cancer patients with cognitive problems and relatively low physical activity levels (≤150 minutes moderate to vigorous physical activity per week), divided into an exercise (N = 91) or control group (N = 90). FIELD STRENGTH/SEQUENCE: Two-dimensional echo planar pseudo-continuous arterial spin labeling CBF sequence at 3 T. ASSESSMENT: The 6-month long intervention consisted of (supervised) aerobic and strength training, 4 × 1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after 6 months included gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Physical fitness and memory function were also assessed. Subgroup analyses were performed in patients with high fatigue levels at baseline. STATISTICAL TESTS: Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS: There was a significant improvement in physical fitness (VO2peak in mL/minute/kg) in the intervention group (N = 53) compared to controls (N = 51, ß = 1.47 mL/minute/kg, 95% CI: 0.44-2.50). However, no intervention effects on CBF were found (eg, whole brain: P = 0.565). Highly fatigued patients showed larger but insignificant treatment effects on CBF (eg, whole brain: P = 0.098). Additionally, irrespective of group, a change in physical fitness was positively associated with changes in CBF (eg, whole brain: ß = 0.75, 95% CI: 0.07-1.43). There was no significant relation between CBF changes and changes in memory performance. DATA CONCLUSION: The exercise intervention did not affect CBF of cognitively affected breast cancer patients. A change in physical fitness was associated with changes in CBF, but changes in CBF were not associated with memory functioning. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 5.

Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

Instability Severity Index Score predicts recurrent shoulder instability after arthroscopic Bankart repair.

PURPOSE: The Instability Severity Index (ISI) Score was developed to preoperatively assess the risk of recurrent shoulder instability after an arthroscopic Bankart repair. This study aims to validate the use of ISI Score for predicting the risk of recurrence after an arthroscopic Bankart repair in a heterogeneous population and proposes an appropriate cut-off point for treating patients with an arthroscopic Bankart repair or otherwise. METHODS: This study analysed 99 shoulders after a traumatic dislocation that underwent arthroscopic Bankart repair with at least 3 years follow-up. Patients were divided into subcategories based on their respective ISI Score. Recurrence includes either a postoperative dislocation or perceived instability. RESULTS: The overall recurrence rate was found to be 26.3%. A significant correlation was identified between ISI Score and the recurrence rate (odds ratio [OR]: 1.545, 95% confidence interval [CI]: 1.231-1.939, p < 0.001). Furthermore, ISI Score 4-6 (OR: 4.498, 95% CI: 1.866-10.842, p < 0.001) and ISI Score > 6 (OR: 7.076, 95% CI: 2.393-20.924, p < 0.001) both had a significantly higher risk of recurrence compared to ISI Score 0-3. In ISI Score subcategories 0-3, 4-6 and >6, the recurrence rate was, respectively, 15.4%, 40.7% and 71.4%. CONCLUSION: ISI Score has predictive value in determining the recurrence risk of shoulder instability following an arthroscopic Bankart repair in a heterogeneous population. Based on the findings of this study, we recommend using arthroscopic Bankart repair in patients with ISI Score 0-3. Clinical and shared decision-making are essential in the group with ISI Score 4-6, since the recurrence rate is significantly higher than in patients with ISI Score 0-3. Arthroscopic Bankart repair is not suitable for patients with ISI Score > 6. LEVEL OF EVIDENCE: Level III.

Routine transthoracic echocardiography in ischaemic stroke or transient ischaemic attack of undetermined cause: a prospective multicentre study.

BACKGROUND: Guidelines recommend routine transthoracic echocardiography (TTE) after ischaemic stroke or transient ischaemic attack of undetermined cause; yet, only limited scientific evidence exists. Therefore, we aimed to determine in these patients the prevalence of TTE-detected major cardiac sources of embolism (CSE), which are abnormalities leading to therapeutic changes. METHODS: Six Dutch hospitals conducted a prospective observational study that enrolled patients with ischaemic stroke or transient ischaemic attack of undetermined cause. Patients underwent TTE after comprehensive diagnostic evaluation on stroke units, including blood chemistry, 12-lead electrocardiogram (ECG), ≥ 24 h continuous ECG monitoring, brain imaging and cervical artery imaging. Primary outcome measure was the proportion of patients with TTE-detected major CSE. RESULTS: From March 2018 to October 2020, 1084 patients, aged 66.6 ± 12.5 years, were enrolled; 456 (42.1%) patients were female and 869 (80.2%) had ischaemic stroke. TTE detected major CSE in only 11 (1.0%) patients. Ten (90.9%) of these patients also had major ECG abnormalities (previous infarction, major repolarisation abnormalities, or previously unknown left bundle branch block) that would have warranted TTE assessment regardless of stroke evaluation. Such ECG abnormalities were present in 11.1% of the total study population. A single patient (0.1%) showed a major CSE despite having no ECG abnormality. CONCLUSIONS: This multicentre cross-sectional study in patients who-after workup on contemporary stroke units-were diagnosed with ischaemic stroke or transient ischaemic attack of undetermined cause found TTE-detected major CSE in only 1% of all patients. Most of these patients also had major ECG abnormalities. These findings question the value of routine TTE assessment in this clinical setting.

A retrospective analysis of the association of effort-independent cardiopulmonary exercise test variables with postoperative complications in patients who underwent elective colorectal surgery.

PURPOSE: This study aimed to investigate the association of effort-independent variables derived from the preoperative cardiopulmonary exercise test (CPET) with 30-day postoperative complications after elective colorectal surgery. METHODS: A multicenter (n=4) retrospective explorative study was performed using data of patients who completed a preoperative CPET and underwent elective colorectal surgery. The preoperative slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2-slope) and the oxygen uptake efficiency slope (OUES), as well as 30-day postoperative complications, were assessed. Multivariable logistic regression analyses and receiver operating characteristic (ROC) curves were used to investigate the prognostic value of the relationship between these preoperative CPET-derived effort-independent variables and postoperative complications. RESULTS: Data from 102 patients (60.1% males) with a median age of 72.0 (interquartile range 67.8-77.4) years were analyzed. Forty-four patients (43.1%) had one or more postoperative complications (of which 52.3% general and 77.3% surgical complications). Merely 10 (9.8%) patients had a general complication only. In multivariate analysis adjusted for surgical approach (open versus minimally invasive surgery), the VE/VCO2-slope (odds ratio (OR) 1.08, confidence interval (CI) 1.02-1.16) and OUES (OR 0.94, CI 0.89-1.00) were statistically significant associated with the occurrence of 30-day postoperative complications. CONCLUSION: The effort-independent VE/VCO2-slope and OUES might be used to assist in future preoperative risk assessment and could especially be of added value in patients who are unable or unwilling to deliver a maximal cardiorespiratory effort. Future research should reveal the predictive value of these variables individually and/or in combination with other prognostic (CPET-derived) variables for postoperative complications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05331196.

Evaluation of Exacerbation and Symptom-Free Time in Patients with COPD.

In clinical practice, clinicians mainly focus on Chronic Obstructive Pulmonary Disease (COPD) exacerbations and symptoms, while patients may prefer to evaluate periods free of COPD exacerbations and deteriorated symptoms. The latter would suit the positive health approach that centralizes people and their beliefs. We aimed to identify patient characteristics and health outcomes relating to: 1) COPD exacerbation-free days; 2) days with no more symptoms than usual; and 3) combined COPD exacerbation and comorbid flare-up-free days (i.e. chronic heart failure, anxiety, depression flare-ups) using negative binomial regression analyzes. Data were obtained from two self-management intervention trials including COPD patients with and without comorbidities. 313 patients (mean age 66.0 years, 63.6% male, 68.7% comorbidity) were included. Better baseline chronic respiratory questionnaire (CRQ) fatigue (incidence rate ratio (IRR) = 1.03 (95% CI 1.01-1.05), p = 0.02) and mastery scores (IRR = 1.03 (95% CI 1.00-1.06), p = 0.04) and fewer courses of antibiotics (IRR = 0.95 (95% CI 0.94-0.96), p < 0.01) were related to more COPD exacerbation-free days. Additionally, better baseline CRQ fatigue (IRR = 1.05 (95% CI 1.00-1.10), p = 0.04) and mastery scores (IRR = 1.06 (95% CI 1.00-1.12), p = 0.04), fewer courses of antibiotics (IRR = 0.94 (95% CI 0.91-0.96), p < 0.01), and improved CRQ dyspnea scores over 12 months of follow-up (IRR = 1.07 (95% CI 1.01-1.12), p < 0.01) were correlated to more days free of deteriorated symptoms. Less baseline dyspnea (modified Medical Research Council score) (IRR = 0.95 (95% CI 0.92-0.98), p < 0.01) and fewer courses of antibiotics (IRR = 0.94 (95% CI 0.93-0.95), p < 0.01) were associated with more combined COPD exacerbation and comorbid flare-up-free days. Healthcare professionals should be aware that less fatigue and better mastering of COPD relate to more exacerbation and symptom-free time in COPD patients.

Atrial fibrillation detected with outpatient cardiac rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause.

OBJECTIVES: Guidelines advise cardiac rhythm monitoring for 3 up to 30 days for detecting atrial fibrillation (AF) in patients with ischemic stroke of undetermined cause. However, the optimal monitoring duration is unknown. We aimed to determine the AF detection rate during 7-day outpatient cardiac rhythm monitoring in this patient group. METHODS: Participants from a large tertiary hospital in a prospective observational study (ATTEST) underwent outpatient cardiac rhythm monitoring after a negative standard diagnostic evaluation (i.e., 12-lead electrocardiogram and in-hospital telemetry). Primary outcome was the rate of newly detected AF. RESULTS: We examined 373 patients [age: 67.8±11.6 years; women: 166(44.5%); stroke: 278(74.5%)]. Median monitoring duration was 7 days (Inter Quartile Range (IQR) 7-7), performed after median of 36 days (IQR 27-47). AF was newly detected in 17(4.6%) patients, 5.4% of patients with ischemic stroke and 2.1% of patients with TIA. 53% of AF was detected on day-1, after day-3 73% of new AF was found. First AF episodes were detected up to day-7. Diabetes and increasing age were independent predictors of new AF. CONCLUSION: After ischemic stroke or TIA of undetermined cause, 7-day outpatient cardiac rhythm monitoring detected new AF in 4.6%. Patients with AF had significantly more cardiovascular risk factors. Although about 50% of first AF episodes occurred during the first day of monitoring, new AF was detected up to day-7, implying that the recommended minimum of 3 days cardiac rhythm monitoring after ischemic stroke of undetermined cause is insufficient. Subsequent long-term rhythm monitoring should be considered in selected patients.

Effects of Community-based Exercise Prehabilitation for Patients Scheduled for Colorectal Surgery With High Risk for Postoperative Complications: Results of a Randomized Clinical Trial.

OBJECTIVE: To assess the effects of a 3-week community-based exercise program on 30-day postoperative complications in high-risk patients scheduled for elective colorectal resection for (pre)malignancy. SUMMARY BACKGROUND DATA: Patients with a low preoperative aerobic fitness undergoing colorectal surgery have an increased risk of postoperative complications. It remains, however, to be demonstrated whether prehabilitation in these patients reduces postoperative complications. METHODS: This 2-center, prospective, single-blinded randomized clinical trial was carried out in 2 large teaching hospitals in the Netherlands. Patients (≥60 years) with colorectal (pre)malignancy scheduled for elective colorectal resection and with a score ≤7 metabolic equivalents on the veterans-specific activity questionnaire were randomly assigned to the prehabilitation group or the usual care group by using block-stratified randomization. An oxygen uptake at the ventilatory anaerobic threshold <11 mL/kg/min at the baseline cardiopulmonary exercise test was the final inclusion criterion. Inclusion was based on a power analysis. Patients in the prehabilitation group participated in a personalized 3-week (3 sessions per week, nine sessions in total) supervised exercise program given in community physical therapy practices before colorectal resection. Patients in the reference group received usual care. The primary outcome was the number of patients with one or more complications within 30 days of surgery, graded according to the Clavien-Dindo classification. Data were analyzed on an intention-to-treat basis. RESULTS: Between February 2014 and December 2018, 57 patients [30 males and 27 females; mean age 73.6 years (standard deviation 6.1), range 61-88 years] were randomized to either prehabilitation (n = 28) or usual care (n = 29). The rate of postoperative complications was lower in the prehabilitation group (n = 12, 42.9%) than in the usual care group (n = 21, 72.4%, relative risk 0.59, 95% confidence interval 0.37-0.96, P = 0.024). CONCLUSIONS: Exercise prehabilitation reduced postoperative complications in high-risk patients scheduled to undergo elective colon resection for (pre)malignancy. Prehabilitation should be considered as usual care in high-risk patients scheduled for elective colon, and probably also rectal, surgery.

The clinical relevance of various methods of classifying ipsilateral breast tumour recurrence as either true local recurrence or new primary.

PURPOSE: Describes the relevance of -various classification methods for ipsilateral breast tumour recurrence (IBTR) as either true recurrence (TR) or new primary (NP) on both disease-specific survival (DSS) and distant metastasis-free survival (DMFS). METHOD: Two hundred and thirty-four of 4359 women undergoing breast-conserving therapy experienced IBTR. We compared the impact of four known classification methods and two newly created classification methods. RESULTS: For three of the methods, a better DSS was observed for NP compared to TR with the hazard ratio (HR) ranging from 0.5 to 0.6. The new Twente method classification, comprising all classification criteria of three known methods, and the new Morphology method, using only morphological criteria, had the best HR and confidence interval with a HR 0.5 (95% CI 0.2-1.0) and a HR 0.5 (95% CI 0.3-1.1), respectively. For DMFS, the HR for NP compared to TR ranged from 0.6 to 0.9 for all six methods. The new Morphology method and the Twente method noted the best HR and confidence intervals with a HR 0.6 (95% CI 0.3-1.1) and a HR 0.6 (95% CI 0.4-1.2), respectively. CONCLUSION: IBTR classified as TR or NP has a prognostic value for both DSS and DMFS, but depends on the classification method used. Developing and validating a generally accepted form of classification are imperative for using TR and NP in clinical practice.

Clinical relevance of the timing of radiotherapy after breast-conserving surgery : Results of a large, single-centre, population-based cohort study.

PURPOSE: To investigate the effect of the timing of radiation therapy after breast-conserving surgery in relation to distant metastasis-free survival and disease-specific survival. METHODS: The analysis was performed in relation to 4189 women all undergoing breast-conserving therapy (BCT). Three groups were defined with respect to lymph node status and the use of adjuvant systemic therapy (AST). Patients were categorized into time intervals: < 37 days, 37-53 days, 54-112 days and > 112 days. RESULTS: For women without lymph node metastases and with favourable characteristics aged > 55 years, an improved treatment efficacy was noted when starting radiotherapy with a time interval of < 37 days. The same was observed for women with lymph nodes metastases receiving AST aged ≤ 50 years. Finally, for women aged > 50 years with negative lymph node status but with unfavourable characteristics and receiving AST, an improved treatment efficacy was noted when starting radiotherapy after a time interval of ≥ 37 days. CONCLUSION: The results of our study further support the hypothesis that the timing of radiotherapy may have an impact on treatment efficacy and that further studies (preferably randomized trials) are indicated.

Can the response to a single dose of beclomethasone dipropionate predict the outcome of long-term treatment in childhood exercise-induced bronchoconstriction?

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is a frequent and highly specific symptom of childhood asthma. Inhaled corticosteroids (ICS) are the mainstay of controller therapy for EIB and asthma; however, a proportion of asthmatic children and adolescents is less responsive to ICS. We hypothesized that a single dose response to ICS could function as a predictor for individual long-term efficacy of ICS. OBJECTIVE: To assess the predictive value of the bronchoprotective effect of a single-dose beclomethasone dipropionate (BDP) against EIB for the bronchoprotective effect of 4 weeks of treatment, using an exercise challenge test (ECT). METHODS: Thirty-two steroid-naïve children and adolescents aged 6 to 18 years with EIB were included in this prospective cohort study. They performed an ECT at baseline, after a single-dose BDP (200µg) and after 4 weeks of BDP treatment (100 µg twice daily) to assess EIB severity. RESULTS: The response to a single-dose BDP on exercise-induced fall in FEV1 showed a significant correlation with the response on exercise-induced fall in FEV1 after 4 weeks of BDP treatment (r = .38, p = .004). A reduction in post-exercise fall in FEV1 of more than 8% after a single-dose BDP could predict BDP efficacy against EIB after 4 weeks of treatment with a positive predictive value of 100% (CI: 86.1-100%) and a negative predictive value of 29.4% (CI: 11.7%-53.7%). CONCLUSION: We found that the individual response to a single-dose BDP against EIB has a predictive value for the efficacy of long-term treatment with BDP. This could support clinicians in providing personalized management of EIB in childhood asthma.

The association between preoperative body composition and aerobic fitness in patients scheduled for colorectal surgery.

AIM: Although cardiopulmonary exercise testing (CPET) is considered the gold standard, a preoperative abdominal CT scan might also provide information concerning preoperative aerobic fitness for risk assessment. This study aimed to investigate the association between preoperative CT-scan-derived body composition variables and preoperative CPET variables of aerobic fitness in colorectal surgery. METHOD: In this retrospective cohort study, CT images at level L3 were analysed for skeletal muscle mass, skeletal muscle radiation attenuation, visceral adipose tissue (VAT) mass and subcutaneous adipose tissue mass. Regression analyses were performed to investigate the relation between CT-scan-derived body composition variables, CPET-derived aerobic fitness and other preoperative patient-related variables. Logistic regression analysis was performed to predict a preoperative anaerobic threshold (AT) ≤ 11.1 ml/kg/min as cut-off for having a high risk for postoperative complications. RESULTS: Data from 78 patients (45 men; mean [SD] age 74.5 [6.4 years]) were analysed. A correlation coefficient of 0.55 was observed between absolute AT and skeletal muscle mass index. Absolute AT (R2 of 51.1%) was lower in patients with a lower skeletal muscle mass index, together with higher age, lower body mass and higher American Society of Anesthesiologists (ASA) score. Higher ASA score (odds ratio 5.64; P = 0.033) and higher VAT mass (odds ratio 1.02; P = 0.036) were associated with an increased risk of an AT ≤ 11.1 ml/kg/min. CONCLUSION: Body composition variables from the preoperative CT scan were moderately associated with preoperative CPET-derived aerobic fitness. Higher ASA score and higher VAT mass were associated with an increased risk of an AT ≤ 11.1 ml/kg/min.

Self-management interventions for people with chronic obstructive pulmonary disease.

BACKGROUND: Self-management interventions help people with chronic obstructive pulmonary disease (COPD) to acquire and practise the skills they need to carry out disease-specific medical regimens, guide changes in health behaviour and provide emotional support to enable them to control their disease. Since the 2014 update of this review, several studies have been published. OBJECTIVES: Primary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of health-related quality of life (HRQoL) and respiratory-related hospital admissions. To evaluate the safety of COPD self-management interventions compared to usual care in terms of respiratory-related mortality and all-cause mortality. Secondary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of other health outcomes and healthcare utilisation. To evaluate effective characteristics of COPD self-management interventions. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, EMBASE, trials registries and the reference lists of included studies up until January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-randomised trials (CRTs) published since 1995. To be eligible for inclusion, self-management interventions had to include at least two intervention components and include an iterative process between participant and healthcare provider(s) in which goals were formulated and feedback was given on self-management actions by the participant. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. We contacted study authors to obtain additional information and missing outcome data where possible. Primary outcomes were health-related quality of life (HRQoL), number of respiratory-related hospital admissions, respiratory-related mortality, and all-cause mortality. When appropriate, we pooled study results using random-effects modelling meta-analyses. MAIN RESULTS: We included 27 studies involving 6008 participants with COPD. The follow-up time ranged from two-and-a-half to 24 months and the content of the interventions was diverse. Participants' mean age ranged from 57 to 74 years, and the proportion of male participants ranged from 33% to 98%. The post-bronchodilator forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of participants ranged from 33.6% to 57.0%. The FEV1/FVC ratio is a measure used to diagnose COPD and to determine the severity of the disease. Studies were conducted on four different continents (Europe (n = 15), North America (n = 8), Asia (n = 1), and Oceania (n = 4); with one study conducted in both Europe and Oceania). Self-management interventions likely improve HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score (lower score represents better HRQoL) with a mean difference (MD) from usual care of -2.86 points (95% confidence interval (CI) -4.87 to -0.85; 14 studies, 2778 participants; low-quality evidence). The pooled MD of -2.86 did not reach the SGRQ minimal clinically important difference (MCID) of four points. Self-management intervention participants were also at a slightly lower risk for at least one respiratory-related hospital admission (odds ratio (OR) 0.75, 95% CI 0.57 to 0.98; 15 studies, 3263 participants; very low-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over a mean of 9.75 months' follow-up was 15 (95% CI 8 to 399) for participants with high baseline risk and 26 (95% CI 15 to 677) for participants with low baseline risk. No differences were observed in respiratory-related mortality (risk difference (RD) 0.01, 95% CI -0.02 to 0.04; 8 studies, 1572 participants ; low-quality evidence) and all-cause mortality (RD -0.01, 95% CI -0.03 to 0.01; 24 studies, 5719 participants; low-quality evidence). We graded the evidence to be of 'moderate' to 'very low' quality according to GRADE. All studies had a substantial risk of bias, because of lack of blinding of participants and personnel to the interventions, which is inherently impossible in a self-management intervention. In addition, risk of bias was noticeably increased because of insufficient information regarding a) non-protocol interventions, and b) analyses to estimate the effect of adhering to interventions. Consequently, the highest GRADE evidence score that could be obtained by studies was 'moderate'. AUTHORS' CONCLUSIONS: Self-management interventions for people with COPD are associated with improvements in HRQoL, as measured with the SGRQ, and a lower probability of respiratory-related hospital admissions. No excess respiratory-related and all-cause mortality risks were observed, which strengthens the view that COPD self-management interventions are unlikely to cause harm. By using stricter inclusion criteria, we decreased heterogeneity in studies, but also reduced the number of included studies and therefore our capacity to conduct subgroup analyses. Data were therefore still insufficient to reach clear conclusions about effective (intervention) characteristics of COPD self-management interventions. As tailoring of COPD self-management interventions to individuals is desirable, heterogeneity is and will likely remain present in self-management interventions. For future studies, we would urge using only COPD self-management interventions that include iterative interactions between participants and healthcare professionals who are competent using behavioural change techniques (BCTs) to elicit participants' motivation, confidence and competence to positively adapt their health behaviour(s) and develop skills to better manage their disease. In addition, to inform further subgroup and meta-regression analyses and to provide stronger conclusions regarding effective COPD self-management interventions, there is a need for more homogeneity in outcome measures. More attention should be paid to behavioural outcome measures and to providing more detailed, uniform and transparently reported data on self-management intervention components and BCTs. Assessment of outcomes over the long term is also recommended to capture changes in people's behaviour. Finally, information regarding non-protocol interventions as well as analyses to estimate the effect of adhering to interventions should be included to increase the quality of evidence.

Impaired Visual Emotion Recognition After Minor Ischemic Stroke.

OBJECTIVE: To assess the prevalence of impaired visual emotion recognition in patients who have experienced a minor ischemic stroke in the subacute phase and to determine associated factors of impaired visual emotion recognition. DESIGN: A prospective observational study. SETTING: Stroke unit of a teaching hospital. PARTICIPANTS: Patients with minor ischemic stroke (N=112). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients with minor stroke underwent a neuropsychological assessment in the subacute phase for visual emotion recognition by the Ekman 60 Faces Test and for general cognition. Univariable linear regression analyses were performed to identify associated factors of emotion recognition impairment. RESULTS: In 112 minor stroke patients, we found a prevalence of 25% of impaired visual emotion recognition. This was significantly correlated with impaired general cognition. Nevertheless, 10.9% of patients with normal general cognition still had impaired emotion recognition. Mood was negatively associated. Stroke localization, hemisphere side, and sex were not associated. CONCLUSION: Impaired visual emotion recognition is found in about one-quarter of patients with minor ischemic stroke.

Applying the electronic nose for pre-operative SARS-CoV-2 screening.

BACKGROUND: Infection with SARS-CoV-2 causes corona virus disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19-positive and negative persons based on volatile organic compounds (VOCs) analysis. METHODS: Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, the presence of SARS-CoV-2-specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine learning and used for pattern recognition. The result is a value between - 1 and + 1, indicating the infection probability. RESULTS: 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96. CONCLUSIONS: The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery.

Use and usability of the dr. Bart app and its relation with health care utilisation and clinical outcomes in people with knee and/or hip osteoarthritis.

BACKGROUND: Self-management is of paramount importance in the non-surgical treatment of knee/hip osteoarthritis (OA). Modern technologies offer the possibility of 24/7 self-management support. We developed an e-self-management application (dr. Bart app) for people with knee/hip OA. The aim of this study was to document the use and usability of the dr. Bart app and its relation with health care utilisation and clinical outcomes in people with knee/hip OA. METHODS: For this study we used backend data for the first 26 weeks of use by the intervention group (N = 214) of an RCT examining the effectiveness of the dr. Bart app. A central element of the dr. Bart app is that it proposes a selection of 72 preformulated goals for health behaviours based on the 'tiny habits method' (e.g. after lunch I rise 12 times from my chair to train my leg muscles). The usability of the app was measured using the System Usability Scale questionnaire (SUS), on a scale of 0-100. To assess the association between the intensity of use of the app and health care utilisation (i.e., consultations in primary or secondary health care) and clinical outcomes (i.e., self-management behaviour, physical activity, health-related quality of life, illness perceptions, symptoms, pain, activities of daily living) we calculated Spearman rank correlation coefficients. RESULTS: Of the 214 participants, 171 (80%) logged in at least once with 151 (71%) choosing at least one goal and 114 (53%) completing at least one goal during the 26 weeks. Of those who chose at least one goal, 56 participants (37%) continued to log in for up to 26 weeks, 12 (8%) continued to select new goals from the offered goals and 37 (25%) continued to complete goals. Preformulated goals in the themes of physical activity (e.g., performing an exercise from the exercises library in the app) and nutrition (e.g., 'eat two pieces of fruit today') were found to be most popular with users. The mean usability scores (standard deviation) at the three and six month follow-ups were 65.9 (16.9) and 64.5 (17.5), respectively. The vast majority of associations between the intensity of use of the dr. Bart app and target outcomes were weak at ρ < (-) 0.25. CONCLUSIONS: More than one-third of people with knee/hip OA who started using the app, continued to use it up to 26 weeks, though usability could be improved. Patients appear to have preferences for goals related to physical activity and nutrition, rather than for goals related to vitality and education. We found weak/no associations between the intensity of use of the dr. Bart app and health care utilisation and clinical outcomes. TRIAL REGISTRATION: (21 September 2017): Dutch Trial Register (Trial Number NTR6693/NL6505 ).

Predicting Mortality in COPD with Validated and Sensitive Biomarkers; Fibrinogen and Mid-Range-Proadrenomedullin (MR-proADM).

Although fibrinogen is a FDA qualified prognostic biomarker in COPD, it still lacks sufficient resolution to be clinically useful. Next to replication of findings in different cohorts also the combination with other validated biomarkers should be investigated. Therefore, the aim of this study was to confirm in a large well-defined population of COPD patients whether fibrinogen can predict mortality and whether a combination with the biomarker MR-proADM can increase prognostic accuracy. From the COMIC cohort study we included COPD patients with a blood sample obtained in stable state (n = 640) and/or at hospitalization for an acute exacerbation of COPD (n = 262). Risk of death during 3 years of follow up for the separate and combined biomarker models was analyzed with Cox regression. Furthermore, logistic regression models for death after one year were constructed. When both fibrinogen and MR-proADM were included in the survival model, a doubling in fibrinogen and MR-proADM levels gave a 2.2 (95% CI 1.3-3.7) and 2.1 (95% CI 1.5-3.0) fold increased risk of dying, respectively. The prediction model for death after 1 year improved significantly when MR-proADM was added to the model with fibrinogen (AUC increased from 0.78 to 0.83; p = 0.02). However, the combined model was not significantly more adequate than the model with solely MR-proADM (AUC 0.83 vs 0.82; p = 0.34). The study suggests that MR-proADM is more promising than fibrinogen in prediciting mortality. Adding fibrinogen to a model containing MR-proADM does not significantly increase the predictive capacity of the model.

Long-term effectiveness of web-based cognitive behavioral therapy for patients with eating disorders.

PURPOSE: To evaluate the long-term effectiveness of a web-based therapist-delivered cognitive behavioral therapy (CBT) for patients with eating disorders (ED). METHODS: We used follow-up data from a randomized controlled trial that evaluated a web-based CBT on ED psychopathology and related health, compared to a waiting list control (WL) condition. As participants of the WL condition started the intervention after their waiting period, follow-up data included participants from both groups. The primary outcome was change from baseline, at 3, 6, and 12-month intervals in ED psychopathology, analyzed using mixed models for repeated measures. Secondary outcomes included body dissatisfaction, BMI, physical health, mental health, self-esteem, quality of life, and social functioning. RESULTS: The population comprised 212 participants in total, in three subgroups: bulimia nervosa (BN; n = 44), binge eating disorder (BED; n = 83), and ED not otherwise specified (EDNOS; n = 85). Treatment effects were sustained during follow-up, with generally large effect sizes for the reduction of ED psychopathology and body dissatisfaction, and small to moderate effect sizes for physical and mental health, self-esteem, social functioning, and quality of life. Most effects were found for all three subgroups, except for long-term improvements in self-esteem and quality of life among participants with BN and EDNOS. CONCLUSION: This study showed long-term sustainability of treatment effects up to 1-year post-treatment of a web-based therapist-delivered CBT for patients with various ED. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series analysis, with intervention. UNIQUE CLINICAL TRIAL NUMBER: NTR2415-Dutch Trial Registry ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2415 ).

The Mitotic Activity Index in combination with Her2neu: a strong prognosticator in breast cancer.

PURPOSE: The aim of this study is to evaluate the prognostic value of the Mitotic Activity Index (MAI) in combination with the human epidermal growth factor receptor (Her2) for distant metastases-free survival (DMFS) and disease-specific survival (DSS) in breast cancer and compare it with the immunohistochemically (IHC) profile types. METHODS: Analyses were based on 2.923 breast-conserving breast cancer specimens with known MAI, Her2 status, and hormone receptor status, resulting in 2.678 Her2MAI combinations, MAI ≤ 12/Her2negative, MAI > 12/Her2negative, MAI > 12/Her2positive, and MAI ≤ 12/Her2positive, and 2.560 IHC profile types, luminal A, luminal B, triple negative, and non-luminal Her2positive. RESULTS: For DMFS, the MAI > 12/Her2negative combination showed a significantly worse outcome in multivariate analyses compared to the MAI ≤ 12/Her2negative combination. None of the IHC profile types showed significantly different outcomes for DMFS and DSS as compared to luminal A. We performed a separate analysis on age and lymph node status. The significance of MAI > 12/Her2negative seems to be limited to women ≤ 55 years for both DMFS and DSS. However, with respect to DSS, this seems to be limited to node negative cases. The IHC profile types for DSS, luminal B showed a significantly worse outcome for women > 55 years compared to that for luminal A, although it showed rather wide confidence interval. CONCLUSION: The MAI > 12/Her2negative combination seems to be a strong prognosticator for DMFS and DSS, particularly for women ≤ 55 years. However, none of the IHC profile types seems to be a prognosticator in breast cancer.