Outcome prognostication in traumatic brain injury (TBI) is important but challenging due to heterogeneity of the disease. The aim of this systematic review is to present the current state-of-the-art ...on prognostic models for outcome after moderate and severe TBI and evidence on their validity. We searched for studies reporting on the development, validation or extension of prognostic models for functional outcome after TBI with Glasgow Coma Scale (GCS) ≤12 published between 2006-2018. Studies with patients age ≥14 years and evaluating a multi-variable prognostic model based on admission characteristics were included. Model discrimination was expressed with the area under the receiver operating characteristic curve (AUC), and model calibration with calibration slope and intercept. We included 58 studies describing 67 different prognostic models, comprising the development of 42 models, 149 external validations of 31 models, and 12 model extensions. The most common predictors were GCS (motor) score (
= 55), age (
= 54), and pupillary reactivity (
= 48). Model discrimination varied substantially between studies. The International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) models were developed on the largest cohorts (8509 and 10,008 patients, respectively) and were most often externally validated (
= 91), yielding AUCs ranging between 0.65-0.90 and 0.66-1.00, respectively. Model calibration was reported with a calibration intercept and slope for seven models in 53 validations, and was highly variable. In conclusion, the discriminatory validity of the IMPACT and CRASH prognostic models is supported across a range of settings. The variation in calibration, reflecting heterogeneity in reliability of predictions, motivates continuous validation and updating if clinical implementation is pursued.
Objective To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease ...control in patients with rheumatoid arthritis compared with usual care.Design Randomised controlled, open label, non-inferiority strategy trial.Setting Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014.Participants 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care.Interventions Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated.Main outcome measures Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events.Results Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval −12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care.Conclusions A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.Trial registration Dutch trial register (www.trialregister.nl), NTR 3216.
Background:
Some children born SGA show advanced bone age (BA) during GH treatment. ACAN-gene mutations have been described in children with idiopathic short stature and advanced BA.
Objective:
To ...determine presence of ACAN-gene mutations in short SGA children with advanced BA and to assess the response to GH treatment.
Methods:
BA assessment in 290 GH-treated SGA children and ACAN-sequencing in 29 children with advanced BA of ≥0.5 years compared to calendar age.
Results:
ACAN-gene mutations were found in 4/29SGA children with advanced BA (13.8%). Mutations were related to the characteristics: midface hypoplasia(P=0.003), joint problems(P=0.010), broad great toes(P=0.003). Children with advanced BA having ≤1 additional characteristic had no ACAN-gene mutation. Of children with advanced BA and 2 additional characteristics, 50% had an ACAN-gene mutation. Of children with advanced BA and 3 of these characteristics, 100% had an ACAN-gene mutation. All GH-treated children with ACAN-gene mutations received additional GnRHa treatment for 2 years from onset of puberty. At adult height, 1 girl was 5 cm taller than her mother and 1 boy was 8 cm taller than his father with the same ACAN-gene mutation. In boys, bone maturation was delayed by aromatase inhibitor treatment.
Conclusion:
This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have ACAN-gene mutations. ACAN-gene sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems or broad great toes. Our findings suggest that children with ACAN-gene mutations benefit from GH treatment with 2 years of GnRHa.
We use longitudinal social network data from the Framingham Heart Study to examine the extent to which alcohol consumption is influenced by the network structure. We assess the spread of alcohol use ...in a three-state SIS-type model, classifying individuals as abstainers, moderate drinkers, and heavy drinkers. We find that the use of three-states improves on the more canonical two-state classification, as the data show that all three states are highly stable and have different social dynamics. We show that when modelling the spread of alcohol use, it is important to model the topology of social interactions by incorporating the network structure. The population is not homogeneously mixed, and clustering is high with abstainers and heavy drinkers. We find that both abstainers and heavy drinkers have a strong influence on their social environment; for every heavy drinker and abstainer connection, the probability of a moderate drinker adopting their drinking behaviour increases by Formula: see text and Formula: see text, respectively. We also find that abstinent connections have a significant positive effect on heavy drinkers quitting drinking. Using simulations, we find that while both are effective, increasing the influence of abstainers appears to be the more effective intervention compared to reducing the influence of heavy drinkers.
Purpose
Previous studies found higher levels of pain severity and disability to be associated with higher costs and lower health-related quality of life. However, these findings were based on ...cross-sectional data and little is known about the longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients. This study aims to cover this knowledge gap by exploring these longitudinal relationships in a consecutive cohort.
Methods
Data of 6316 chronic low back pain patients were used. Measurements took place at 3, 6, 9, and 12 months. Pain severity (Numeric pain rating scale; range: 0–100), disability (Oswestry disability index; range: 0–100), health-related quality of life (EQ-5D-3L: range: 0–1), societal and healthcare costs (cost questionnaire) were measured. Using linear generalized estimating equation analyses, longitudinal relationships were explored between: (1) pain severity and health-related quality of life, (2) disability and health-related quality of life, (3) pain severity and societal costs, (4) disability and societal costs, (5) pain severity and healthcare costs, and (6) disability and healthcare costs.
Results
Higher pain and disability levels were statistically significantly related with poorer health-related quality of life (pain intensity: − 0.0041; 95% CI − 0.0043 to − 0.0039; disability: − 0.0096; 95% CI − 0.0099 to − 0.0093), higher societal costs (pain intensity: 7; 95% CI 5 to 8; disability: 23; 95% CI 20 to 27) and higher healthcare costs (pain intensity: 3; 95% CI 2 to 4; disability: 9; 95% CI 7 to 11).
Conclusion
Pain and disability were longitudinally related to health-related quality of life, societal costs, and healthcare costs. Disability had a stronger association with all outcomes compared to pain.
IMPORTANCE: Radiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking. OBJECTIVE: To evaluate the effectiveness of ...radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain. DESIGN, SETTING, AND PARTICIPANTS: Three pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care. INTERVENTIONS: All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-time procedure, but the maximum number of treatments in the trial was 3. MAIN OUTCOMES AND MEASURES: The primary outcome was pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015. RESULTS: Among 681 participants who were randomized (mean age, 52.2 years; 421 women 61.8%, mean baseline pain intensity, 7.1), 599 (88%) completed the 3-month follow-up, and 521 (77%) completed the 12-month follow-up. The mean difference in pain intensity between the radiofrequency denervation and control groups at 3 months was −0.18 (95% CI, −0.76 to 0.40) in the facet joint trial; −0.71 (95% CI, −1.35 to −0.06) in the sacroiliac joint trial; and −0.99 (95% CI, −1.73 to −0.25) in the combination trial. CONCLUSIONS AND RELEVANCE: In 3 randomized clinical trials of participants with chronic low back pain originating in the facet joints, sacroiliac joints, or a combination of facet joints, sacroiliac joints, or intervertebral disks, radiofrequency denervation combined with a standardized exercise program resulted in either no improvement or no clinically important improvement in chronic low back pain compared with a standardized exercise program alone. The findings do not support the use of radiofrequency denervation to treat chronic low back pain from these sources. TRIAL REGISTRATION: trialregister.nl Identifier: NTR3531
Some COVID-19 survivors suffer from persistent pulmonary function impairment, but the extent and associated factors are unclear. This study aimed to characterize pulmonary function impairment three ...to five months after hospital discharge and the association with disease severity. Survivors of COVID-19 after hospitalization to the VieCuri Medical Centre between February and December 2020 were invited for follow-up, three to five months after discharge. Dynamic and static lung volumes, respiratory muscle strength and diffusion capacity were measured. The cohort comprised 257 patients after a moderate (n = 33), severe (n = 151) or critical (n = 73) COVID-19 infection with a median follow-up of 112 days (interquartile range 96-134 days). The main sequelae included reduced diffusion capacity (36%) and reduced maximal expiratory pressure (24%). Critically ill patients were more likely to have reduced diffusion capacity than moderate (OR 8.00, 95% CI 2.46-26.01) and severe cases (OR 3.74, 95% CI 1.88-7.44) and lower forced vital capacity (OR 3.29, 95% CI 1.20-9.06) compared to severe cases. Many COVID-19 survivors, especially after a critical disease course, showed pulmonary function sequelae, mainly DLCO impairments, three to five months after discharge. Monitoring is needed to investigate the persistence of these symptoms and the longer-term implications of the COVID-19 burden.
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.
The definition of an in vivo nodal anatomical baseline is crucial for validation of representative lymph node dissections and accompanying pathology reports of pelvic cancers, as well as for ...assessing a potential therapeutic effect of extended lymph node dissections. Therefore the number, size and distribution of lymph nodes in the pelvis were assessed with high-resolution, large field-of-view, 7 Tesla (T) magnetic resonance imaging (MRI) with frequency-selective excitation. We used 7 T MRI for homogeneous pelvic imaging in 11 young healthy volunteers. Frequency-selective imaging of water and lipids was performed to detect nodal structures in the pelvis. Number and size of detected nodes was measured and size distribution per region was assessed. An average volunteer-normalized nodal size distribution was determined. In total, 564 lymph nodes were detected in six pelvic regions. Mean number was 51.3 with a wide range of 19-91 lymph nodes per volunteer. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% Was 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution. The amount of in vivo visible lymph nodes varies largely between subjects, whereas the normalized size distribution of nodes does not. The presence of many small lymph nodes (less than or equal to2mm) renders representative or complete removal of pelvic lymph nodes to be very difficult. 7T MRI may shift the in vivo detection limits of lymph node metastases in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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