While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of ...beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients.
Abstract Objectives Regardless of the proportion of missing values, complete-case analysis is most frequently applied, although advanced techniques such as multiple imputation (MI) are available. The ...objective of this study was to explore the performance of simple and more advanced methods for handling missing data in cases when some, many, or all item scores are missing in a multi-item instrument. Study Design and Setting Real-life missing data situations were simulated in a multi-item variable used as a covariate in a linear regression model. Various missing data mechanisms were simulated with an increasing percentage of missing data. Subsequently, several techniques to handle missing data were applied to decide on the most optimal technique for each scenario. Fitted regression coefficients were compared using the bias and coverage as performance parameters. Results Mean imputation caused biased estimates in every missing data scenario when data are missing for more than 10% of the subjects. Furthermore, when a large percentage of subjects had missing items (>25%), MI methods applied to the items outperformed methods applied to the total score. Conclusion We recommend applying MI to the item scores to get the most accurate regression model estimates. Moreover, we advise not to use any form of mean imputation to handle missing data.
Several disease-specific questionnaires to measure pain and disability in patients with neck pain have been translated. However, a simple translation of the original version doesn't guarantee similar ...measurement properties. The objective of this study is to critically appraise the quality of the translation process, cross-cultural validation and the measurement properties of translated versions of neck-specific questionnaires.
Bibliographic databases were searched for articles concerning the translation or evaluation of the measurement properties of a translated version of a neck-specific questionnaire. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist and criteria for measurement properties.
The search strategy resulted in a total of 3641 unique hits, of which 27 articles, evaluating 6 different questionnaires in 15 different languages, were included in this study. Generally the methodological quality of the translation process is poor and none of the included studies performed a cross-cultural adaptation. A substantial amount of information regarding the measurement properties of translated versions of the different neck-specific questionnaires is lacking. Moreover, the evidence for the quality of measurement properties of the translated versions is mostly limited or assessed in studies of poor methodological quality.
Until results from high quality studies are available, we advise to use the Catalan, Dutch, English, Iranian, Korean, Spanish and Turkish version of the NDI, the Chinese version of the NPQ, and the Finnish, German and Italian version of the NPDS. The Greek NDI needs cross-cultural validation and there is no methodologically sound information for the Swedish NDI. For all other languages we advise to translate the original version of the NDI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Platinum-based CRT for HPV-neg HNSCC has unique treatment course and outcome pattern.•CRT is often too toxic, in ∼35% of patients the cisplatin-dose plan needed changes.•Switching to carboplatin ...when cisplatin is too toxic seems not beneficial for OS (HR 1.49 vs HR 1.59).•Development of DM was strongly associated with boosting method (SEQ vs SIB; OR 1.91).
Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques.
Retrospective data were collected from a multicenter cohort of 513 patients treated with definitive concurrent platinum-based CRT with curative intent between January 2009 and August 2017. Only patients with HPV-negative advanced stage (III-IV) HNSCC were included. A prognostic model for outcome was developed based on clinical parameters and compared to TNM.
Nearly half of the 513 patients (49%) had an oropharyngeal tumor, often locally advanced (73.3% T3-T4b) and with involvement of the regional lymph nodes (84%). Most patients (84%) received cisplatin as single agent. In total 66% received the planned number of cycles and 75% reached a cumulative cisplatin dose of ≥200 mg/m2. Locoregional control was achieved in 324 (63%) patients during follow-up, and no association with tumor sites was observed (p = 0.48). Overall survival at 5 year follow-up was 47%, with a better survival for laryngeal cancer (p = 0.02) compared to other sites. A model with clinical variables (gender, high pre-treatment weight loss, N2c/N3-stage and <200 mg/m2 dose of cisplatin) provided a noticeably stronger association with overall survival than TNM-staging (C- index 0.68 vs 0.55). Simultaneous Integrated Boosting (SIB) significantly outperformed Sequential Boosting (SEQ) to reduce the development of distant metastasis (SEQ vs SIB: OR 1.91 (1.11–3.26; p = 0.02).
Despite advances in clinical management, more than a third of patients with HPV-negative HNSCC do not complete CRT treatment protocols due to cisplatin toxicity. A model that consists of clinical variables and treatment parameters including cisplatin dose provided the strongest association with overall survival. Since cisplatin toxicity is a major obstacle in completing definitive CRT, the development of alternative and less toxic radiosensitizers is therefore warranted to improve treatment results. The association of RT-boost technique with distant metastasis is an important finding and requires further study.
We aimed to develop a Service Capacity Index for Substance Use Disorders (SCI-SUD) that would reflect the capacity of national health systems to provide treatment for alcohol and drug use disorders, ...in terms of the proportion of available service elements in a given country from a theoretical maximum.
Data were collected through the WHO Global Survey on Progress with Sustainable Development Goals (SDG) Health Target 3.5, conducted between December 2019 and July 2020 to produce the SCI-SUD, based on 378 variables overall.
The SCI-SUD was directly derived for 145 countries. We used multiple imputation to produce comparable SCI-SUD estimates for countries that did not submit data (40 countries) or had very high level of missingness (9 countries). The final SCI-SUD demonstrates considerable consistency and internal stability and is strongly associated with the macro-level economic, healthcare-related and epidemiologic (such as prevalence rates) variables.
The presented methodology represents a step forward in monitoring the global situation in regard to the development of treatment systems for SU disorders, however, further work is warranted to improve the external validity of the measure (e.g., in-depth data generation in countries) and ensure its feasibility for regular reporting (e.g., reducing the number of variables).
The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients ...with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (
= 8 in glioblastoma and
= 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.
Aim
Clinical prediction models need to be validated. In this study, we used simulation data to compare various internal and external validation approaches to validate models.
Methods
Data of 500 ...patients were simulated using distributions of metabolic tumor volume, standardized uptake value, the maximal distance between the largest lesion and another lesion, WHO performance status and age of 296 diffuse large B cell lymphoma patients. These data were used to predict progression after 2 years based on an existing logistic regression model. Using the simulated data, we applied cross-validation, bootstrapping and holdout (
n
= 100). We simulated new external datasets (
n
= 100,
n
= 200,
n
= 500) and simulated stage-specific external datasets (1), varied the cut-off for high-risk patients (2) and the false positive and false negative rates (3) and simulated a dataset with EARL2 characteristics (4). All internal and external simulations were repeated 100 times. Model performance was expressed as the cross-validated area under the curve (CV-AUC ± SD) and calibration slope.
Results
The cross-validation (0.71 ± 0.06) and holdout (0.70 ± 0.07) resulted in comparable model performances, but the model had a higher uncertainty using a holdout set. Bootstrapping resulted in a CV-AUC of 0.67 ± 0.02. The calibration slope was comparable for these internal validation approaches. Increasing the size of the test set resulted in more precise CV-AUC estimates and smaller SD for the calibration slope. For test datasets with different stages, the CV-AUC increased as Ann Arbor stages increased. As expected, changing the cut-off for high risk and false positive- and negative rates influenced the model performance, which is clearly shown by the low calibration slope. The EARL2 dataset resulted in similar model performance and precision, but calibration slope indicated overfitting.
Conclusion
In case of small datasets, it is not advisable to use a holdout or a very small external dataset with similar characteristics. A single small testing dataset suffers from a large uncertainty. Therefore, repeated CV using the full training dataset is preferred instead. Our simulations also demonstrated that it is important to consider the impact of differences in patient population between training and test data, which may ask for adjustment or stratification of relevant variables.
Background The relationship between numerous risk factors and perioperative mortality after cardiovascular surgery has been studied extensively. While improved perioperative survival and fewer ...cardiovascular events have been related to statin therapy, its effect on long-term survival after aneurysm repair remains to be elucidated. The aim of this study is to determine the effect of statin therapy on long-term survival after open and endovascular aneurysm repair and to identify other cardiovascular and patient-related risk factors in this respect. Methods A post-hoc analysis of a randomized trial comparing open and endovascular abdominal aortic aneurysm repair was performed. In this multicenter trial, 351 patients were randomly assigned to undergo either open abdominal aortic aneurysm repair or endovascular repair. Patients who were on lipid-lowering medication at their inclusion in the trial (n = 135) were compared with those who were not (n = 216). Results During 6 years of follow-up, 118 (33.6%) patients died after randomization. Statin therapy, baseline characteristics, Society for Vascular Surgery/International Society for Cardiovascular Surgery risk factors, aneurysm size, reinterventions, antiplatelet or anticoagulant agents, and β-blockers were used to identify prognostic factors influencing survival. After identification of significant factors in a Kaplan-Meier analysis, a multivariable Cox regression analysis was applied. Statin therapy at inclusion in the trial was independently associated with better overall survival after open or endovascular aneurysm repair (hazard ratio HR, 0.5; 95% confidence interval CI, 0.3-0.8; P = .004). Statins were especially associated with fewer cardiovascular deaths (HR, 0.4; 95% CI, 0.2-0.9; P = .025). Several risk factors were associated with poor survival after open and endovascular aneurysm repair: age >70 (HR, 3.4; 95% CI, 2.2-5.0; P < .001), a history of cardiac disease at baseline (HR, 1.9; 95% CI, 1.3-2.8; P = .001), and moderate/severe tobacco use (HR, 1.7; 95% CI, 1.2-2.5; P = .004). Gender, aneurysm size, the need for reintervention, pulmonary disease, renal disease, carotid disease, hypertension, diabetes mellitus, antiplatelet or anticoagulant agents, and β-blockers were not significantly associated with impaired long-term survival ( P > .05). Conclusions Despite the limitations of a post-hoc analysis of a prospectively maintained trial, we conclude that statin therapy at the beginning of the trial is independently associated with improved long-term survival after open or endovascular aneurysm repair, while age above 70 years, a history of cardiovascular disease, and tobacco use are associated with decreased long-term survival.
Background: The objectives of this systematic review are to examine how researchers report missing data in questionnaires and to provide an overview of current methods for dealing with missing data. ...Methods: We included 262 studies published in 2010 in 3 leading epidemiologic journals. Information was extracted on how missing data were reported, types of missing, and methods for dealing with missing data. Results: Seventy-eight percent of the studies lacked clear information about the measurement instruments. Missing data in multi-item instruments were not handled differently from other missing data. Complete-case analysis was most frequently reported (81% of the studies), and the selectivity of missing data was seldom examined. Conclusions: Although there are specific methods for handling missing data in item scores and in total scores of multi-item instruments, these are seldom applied. Researchers mainly use complete-case analysis for both types of missing, which may seriously bias the study results.
Depression and anxiety are common in visually impaired and blind adults, but often remain untreated in those who receive support from low vision service (LVS) organizations. This study aims to ...determine factors associated with discussing mental health by LVS workers.
A self-administered cross-sectional survey in one hundred LVS workers was performed. Data on current practice, symptom attribution, and determinants of the Integrated Change Model (i.e. predisposing and environmental factors, awareness, attitude, self-efficacy, social influence, confidence and barriers) were investigated. Multivariable logistic regression analysis was performed to determine predictors of discussing mental health problems in this population. Subsequently, internal validation was conducted using a bootstrapping method.
Around 80% of the participants often discussed mental health with clients. Five factors were found to predict discussion of mental health: female gender (OR = 4.51; 95% confidence interval (CI) 0.98 to 21.61), higher education (OR = 3.39; CI 1.19 to 9.66), intention to discuss mental health problems (OR = 3.49; CI 1.20 to 10.15), higher self-efficacy (OR = 1.11; CI 1.02 to 1.20), and higher perceived social influence (OR = 1.15; CI 1.05 to 1.27). Good discrimination after internal validation was reflected by the area under the curve (0.850).
Previous studies indicate clients want healthcare providers to initiate discussions about mental health. However, still 20% of LVS workers do not discuss suspected depression or anxiety. In order to improve this, LVS organizations could address mental health as part of their care and provide training to ensure intention to discuss mental health problems, improve self-efficacy and create a supportive environment between colleagues.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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