Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute ...coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
Guidelines have provided positive recommendations for pulmonary rehabilitation after exacerbations of chronic obstructive pulmonary disease (COPD), but recent studies indicate that postexacerbation ...rehabilitation may not always be effective in patients with unstable COPD.
To assess effects of pulmonary rehabilitation after COPD exacerbations on hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life (HRQL) and exercise capacity).
We identified studies through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro (Physiotherapy Evidence Database) and the Cochrane Airways Review Group Register of Trials. Searches were current as of 20 October 2015, and handsearches were run up to 5 April 2016.
Randomised controlled trials (RCTs) comparing pulmonary rehabilitation of any duration after exacerbation of COPD versus conventional care. Pulmonary rehabilitation programmes had to include at least physical exercise (endurance or strength exercise, or both). We did not apply a criterion for the minimum number of exercise sessions a rehabilitation programme had to offer to be included in the review. Control groups received conventional community care without rehabilitation.
We expected substantial heterogeneity across trials in terms of how extensive rehabilitation programmes were (i.e. in terms of number of completed exercise sessions; type, intensity and supervision of exercise training; and patient education), duration of follow-up (< 3 months vs ≥ 3 months) and risk of bias (generation of random sequence, concealment of random allocation and blinding); therefore, we performed subgroup analyses that were defined before we carried them out. We used standard methods expected by Cochrane in preparing this update, and we used GRADE for assessing the quality of evidence.
For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self-management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive.Eight studies involving 810 participants contributed data on hospital readmissions. Moderate-quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I
= 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta-analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I
= 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies.High-quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health-related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) -7.80, 95% CI -12.12 to -3.47; I
= 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High-quality evidence shows that six-minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I
= 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health-related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review.Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event.
Overall, evidence of high quality shows moderate to large effects of rehabilitation on health-related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self-management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality.
To develop and validate a comprehensive complication index (CCI) that integrates all events with their respective severity.
Reporting of surgical complications is inconsistent and often incomplete. ...Most studies fail to provide information about the severity of complications, or inform only on the most severe event, ignoring events of lesser severity.
We used an established classification of complications, adopting methods from operation risk index analysis in marketing research to develop a formula that considers all complications that may occur in a patient. The weights of each grade of complication, defined as median reference values, were obtained from 472 participants, who rated 30 different complications. Validation to assess sensitivity to treatment effects and validity of the CCI was performed by 4 different approaches, based on 1299 patients.
The CCI is calculated as the sum of all complications that are weighted for their severity (multiplication of the median reference values from patients and physicians). The final formula yields a continuous scale to rank the severity of any combination of complications from 0 to 100 in a single patient. The CCI was highly sensitive in detecting treatment effect differences in the context of a randomized trial (effect size detected by CCI vs conventional standardized morbidity outcomes). It also showed a negative correlation with postoperative health status (r = -0.24, P = 0.002), and high correlation with the results of patient-rated single and multiple complications on conjoint analysis (r = 0.94, P < 0.001).
The CCI summarizes all postoperative complications and is more sensitive than existing morbidity endpoints. It may serve as a standardized and widely applicable primary endpoint in surgical trials and other interventional fields of medicine. The CCI can be readily computed on the basis of tabulated complications according to the Clavien-Dindo classification (available at www.assessurgery.com).
Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. This study aimed to evaluate the prevalence and severity of post COVID-19 condition ...(PCC) with novel SARS-CoV-2 variants and after prior vaccination.
We used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses.
We found strong evidence that vaccinated individuals infected with Omicron had reduced odds of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The odds among non-vaccinated individuals were similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants.
The risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies.
The COVID-19 pandemic challenges societies in unknown ways, and individuals experience a substantial change in their daily lives and activities. Our study aims to describe these changes using ...population-based self-reported data about social and health behavior in a random sample of the Swiss population during the COVID-19 pandemic. The aim of the present article is two-fold: First, we want to describe the study methodology. Second, we want to report participant characteristics and study findings of the first survey wave to provide some baseline results for our study.
Our study design is a longitudinal online panel of a random sample of the Swiss population. We measure outcome indicators covering general well-being, physical and mental health, social support, healthcare use and working state over multiple survey waves.
From 8,174 contacted individuals, 2,026 individuals participated in the first survey wave which corresponds to a response rate of 24.8%. Most survey participants reported a good to very good general life satisfaction (93.3%). 41.4% of the participants reported a worsened quality of life compared to before the COVID-19 emergency and 9.8% feelings of loneliness.
The COVID-19 Social Monitor is a population-based online survey which informs the public, health authorities, and the scientific community about relevant aspects and potential changes in social and health behavior during the COVID-19 emergency and beyond. Future research will follow up on the described study population focusing on COVID-19 relevant topics such as subgroup differences in the impact of the pandemic on well-being and quality of life or different dynamics of perceived psychological distress.
The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This ...document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.
This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence ...in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: (1) consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, (2) there is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, (3) we should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and (4) in the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe.
•The application of the Grading of Recommendations Assessments, Development, and Evaluation approach to a number of network meta-analyses in the 3 years since the original guidance publication has led to advances that have strengthened the conceptual basis.•We present, discuss, and illustrate four conceptual advances. These are based on two principles: we need to rate the certainty of the evidence of each pairwise comparison within a network separately and that we need to consider both the direct and indirect evidence contributing to each network estimate.•Although maximizing the efficiency of the process is desirable, as illustrated in the conceptual advances, use of these strategies requires careful judgment.
Alternative nicotine products such as electronic nicotine delivery systems (ENDS) and tobacco heating systems have gained worldwide popularity. Findings suggest ENDS to be probably less harmful than ...combustible cigarettes, but evidence on long-term health effects is still lacking. The potential risk reduction by using tobacco heating systems instead of combustible cigarettes has largely been studied by tobacco industry-sponsored research. Evidence on the extent of risk reduction is key for risk-adapted taxation policies, which will be discussed soon in the Swiss parliament. Evidence on the effects of tax policies in the USA shows that the level of taxation of ENDS, tobacco heating systems and combustible cigarettes has an effect on switches between these products. Therefore, excise taxes influencing one another need to be considered. In Switzerland, tobacco heating systems are currently taxed at a level of 12%, whereas ENDS are not subject to tobacco excise taxation as yet, because they do not meet the legal definition of a tobacco product. This article analyses approaches for imposing taxes on tobacco and nicotine products and possible outcomes, depending on the intended public health goals. At least three tax models can be considered. Tax model A would apply a very small tax on ENDS and a higher tax for tobacco products, which could increase incentives for smokers to switch to vaping but comes with risks of increased vaping initiation among the youth and subsequent switch to or dual use of tobacco products. In contrast, model B would levy a moderate tax on ENDS and an increased tax on tobacco products, which could limit initiation among youth, incentivise to switch from smoking to vaping and discourage dual use. In model C, a comparable tax level for ENDS, tobacco heating systems and combustible cigarettes is levied. This could have overall positive effects in reducing tobacco- and nicotine-associated burden of disease by discouraging initiation in youth, overall consumption and dual use, but could discourage switching to less harmful products. When applying these tax models to current sales prices of these products we found that no public health goal, such as protecting youth and reducing tobacco-associated morbidity and mortality can be achieved. The price of tobacco products is too low to achieve any price differentiation that reflects the different risks associated with ENDS and tobacco products. In order to achieve any public health goal with one of these tax models, prices for tobacco products need to be increased substantially.
The population with multiple chronic conditions is growing. Prior studies indicate that patients with comorbidities are frequently excluded from trials but do not address whether information is ...available in trials to draw conclusions about treatment effects for these patients.
We conducted a literature survey of trials from 11 Cochrane Reviews for four chronic diseases (diabetes, heart failure, chronic obstructive pulmonary disease, and stroke). The Cochrane Reviews systematically identified and summarized trials on the effectiveness of diuretics, metformin, anticoagulants, longacting beta-agonists alone or in combination with inhaled corticosteroids, lipid lowering agents, exercise and diet. Eligible studies were reports of trials included in the Cochrane reviews and additional papers that described the methods of these trials. We assessed the exclusion and inclusion of people with comorbidities, the reporting of comorbidities, and whether comorbidities were considered as potential modifiers of treatment effects. Overall, the replicability of both the inclusion criteria (mean standard deviation (SD): 6.0 (2.1), range (min-max): 1-9.5) and exclusion criteria (mean(SD): 5.3 (2.1), range: 1-9.5) was only moderate. Trials excluded patients with many common comorbidities. The proportion of exclusions for comorbidities ranged from 0-42 percent for heart failure, 0-55 percent for COPD, 0-44 percent for diabetes, and 0-39 percent for stroke. Seventy of the 161 trials (43.5%) described the prevalence of any comorbidity among participants with the index disease. The reporting of comorbidities in trials was very limited, in terms of reporting an operational definition and method of ascertainment for the presence of comorbidity and treatments for the comorbidity. It was even less common that the trials assessed whether comorbidities were potential modifiers of treatment effects.
Comorbidities receive little attention in chronic disease trials. Given the public health importance of people with multiple chronic conditions, trials should better report on comorbidities and assess the effect comorbidities have on treatment outcomes.
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