Introduction
The Glasgow Coma Scale (GCS) provides a structured method for assessment of the level of consciousness. Its derived sum score is applied in research and adopted in intensive care unit ...scoring systems. Controversy exists on the reliability of the GCS. The aim of this systematic review was to summarize evidence on the reliability of the GCS.
Methods
A literature search was undertaken in MEDLINE, EMBASE and CINAHL. Observational studies that assessed the reliability of the GCS, expressed by a statistical measure, were included. Methodological quality was evaluated with the consensus-based standards for the selection of health measurement instruments checklist and its influence on results considered. Reliability estimates were synthesized narratively.
Results
We identified 52 relevant studies that showed significant heterogeneity in the type of reliability estimates used, patients studied, setting and characteristics of observers. Methodological quality was good (
n
= 7), fair (
n
= 18) or poor (
n
= 27). In good quality studies, kappa values were ≥0.6 in 85 %, and all intraclass correlation coefficients indicated excellent reliability. Poor quality studies showed lower reliability estimates. Reliability for the GCS components was higher than for the sum score. Factors that may influence reliability include education and training, the level of consciousness and type of stimuli used.
Conclusions
Only 13 % of studies were of good quality and inconsistency in reported reliability estimates was found. Although the reliability was adequate in good quality studies, further improvement is desirable. From a methodological perspective, the quality of reliability studies needs to be improved. From a clinical perspective, a renewed focus on training/education and standardization of assessment is required.
Measuring the performance of models that predict individualized treatment effect is challenging because the outcomes of two alternative treatments are inherently unobservable in one patient. The ...C-for-benefit was proposed to measure discriminative ability. However, measures of calibration and overall performance are still lacking. We aimed to propose metrics of calibration and overall performance for models predicting treatment effect in randomized clinical trials (RCTs).
Similar to the previously proposed C-for-benefit, we defined observed pairwise treatment effect as the difference between outcomes in pairs of matched patients with different treatment assignment. We match each untreated patient with the nearest treated patient based on the Mahalanobis distance between patient characteristics. Then, we define the E
-for-benefit, E
-for-benefit, and E
-for-benefit as the average, median, and 90
quantile of the absolute distance between the predicted pairwise treatment effects and local-regression-smoothed observed pairwise treatment effects. Furthermore, we define the cross-entropy-for-benefit and Brier-for-benefit as the logarithmic and average squared distance between predicted and observed pairwise treatment effects. In a simulation study, the metric values of deliberately "perturbed models" were compared to those of the data-generating model, i.e., "optimal model". To illustrate these performance metrics, different modeling approaches for predicting treatment effect are applied to the data of the Diabetes Prevention Program: 1) a risk modelling approach with restricted cubic splines; 2) an effect modelling approach including penalized treatment interactions; and 3) the causal forest.
As desired, performance metric values of "perturbed models" were consistently worse than those of the "optimal model" (E
-for-benefit ≥ 0.043 versus 0.002, E
-for-benefit ≥ 0.032 versus 0.001, E
-for-benefit ≥ 0.084 versus 0.004, cross-entropy-for-benefit ≥ 0.765 versus 0.750, Brier-for-benefit ≥ 0.220 versus 0.218). Calibration, discriminative ability, and overall performance of three different models were similar in the case study. The proposed metrics were implemented in a publicly available R-package "HTEPredictionMetrics".
The proposed metrics are useful to assess the calibration and overall performance of models predicting treatment effect in RCTs.
Abstract This study aimed to identify risk factors for long-term sexual dysfunction (SD) after rectal cancer treatment. Patients with resectable rectal cancer were randomised to total mesorectal ...excision with or without preoperative radiotherapy (PRT). Preoperatively and at 3, 6, 12, 18 and 24 months postoperatively, SD scores were filled out in questionnaires. Possible risk factors for postoperative deterioration of sexual functioning, including patients’ demographics, tumour-specific factors and treatment-related variables, were investigated with univariate and multivariable regression analyses. Increase in general SD, erectile dysfunction and ejaculatory problems were reported by 76.4, 79.8 and 72.2 percent of the male patients, respectively. Risk factors were nerve damage, blood loss, anastomotic leakage, PRT and the presence of a stoma. In female patients, increase in general SD, dyspareunia and vaginal dryness were reported by 61.5, 59.1 and 56.6 percent, respectively. This was associated with PRT and the presence of a stoma. SD occurs frequently after rectal cancer treatment and is caused by surgical (nerve) damage with an additional effect of PRT. Patients should be informed preoperatively, and education of surgeons in neuroanatomy may provide the key to the improvement of functional outcome.
The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as ...defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage.
Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve AUC) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia).
The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3–7·8) in the development cohort and 5·0 years (2·2–8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0–75·1) and 5-year melanoma-specific survival was 86·5% (85·3–87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6–67·7) and 83·3% (82·0–84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78–0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79–0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71–0·75) and 0·76 (0·74–0·78), respectively.
Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas.
Erasmus Medical Centre Cancer Institute.
Summary
Studies on the conditional life expectancy of patients with chronic myeloid leukaemia (CML) are lacking. Using data from the Netherlands Cancer Registry, we examined the life expectancy of ...patients with CML in the Netherlands diagnosed during 1989–2018. As of the early 2010s, the life expectancy of patients with CML who survived several years after diagnosis came narrowly close to the general population’s life expectancy, regardless of age. This finding can essentially be ascribed to the introduction and broader application of tyrosine kinase inhibitors (TKIs) and provide optimism to patients with CML who can look forward to a near‐normal life expectancy in a modern TKI era.
Objective
There currently is no disease-modifying therapy for spinocerebellar ataxia type 1 (SCA1). Genetic interventions, such as RNA-based therapies, are being developed but those currently ...available are very expensive. Early evaluation of costs and benefits is, therefore, crucial. By developing a health economic model, we aimed to provide first insights into the potential cost-effectiveness of RNA-based therapies for SCA1 in the Netherlands.
Methods
We simulated disease progression of individuals with SCA1 using a patient-level state-transition model. Five hypothetical treatment strategies with different start and endpoints and level of effectiveness (5–50% reduction in disease progression) were evaluated. Consequences of each strategy were measured in terms of quality-adjusted life years (QALYs), survival, healthcare costs, and maximum costs to be cost effective.
Results
Most QALYs (6.68) are gained when therapy starts during the pre-ataxic stage and continues during the entire disease course. Incremental costs are lowest (− €14,048) if therapy is stopped when the severe ataxia stage is reached. The maximum costs per year to be cost-effective are €19,630 in the “stop after moderate ataxia stage” strategy at 50% effectiveness.
Discussion
Our model indicates that the maximum price for a hypothetical therapy to be cost-effective is considerably lower than currently available RNA-based therapies. Most value for money can be gained by slowing progression in the early and moderate stages of SCA1 and by stopping therapy upon entering the severe ataxia stage. To allow for such a strategy, it is crucial to identify individuals in early stages of disease, preferably just before symptom onset.
Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and ...pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities.
Objectives To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with ...controlled ovarian hyperstimulation in terms of a healthy child.Design Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial.Setting 17 centres in the Netherlands.Participants Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility.Interventions Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation.Main outcome measures The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortalityResults 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation).Conclusions In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates.Trial registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.
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