Chronic subdural hematoma (CSDH) is characterized by an "old" encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura). Recognized risk ...factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data, but lasso regression revealed an association with inflammatory and angiogenic biomarkers in hematoma fluid. We thus suggest that lasso regression should be a recommended statistical method in research on biological processes in CSDH patients.
Chronic subdural hematoma (CSDH) is a relatively common disorder in neurosurgery on elderly patients, though the mechanism that causes the disease remains unclear. Studies have suggested that local ...anticoagulation and inflammatory changes may be important in its pathogenesis. Most studies have used a basic bivariate statistical analysis to assess complex immunological responses in patients with this disorder, hence a more sophisticated multivariate statistical approach might be warranted. Our objective was to assess the association and correlation between the pro- and anti-inflammatory responses in a cohort of patients with chronic subdural hematoma (n=57) using an exploratory and confirmatory factor analysis. Thirteen assigned pro-inflammatory (TNF-α, IL-1β, IL-2, IL-2R, IL-6, IL-7, IL-12, IL-15, IL-17, CCL2, CXCL8, CXCL9 and CXCL10) and five assigned anti-inflammatory (IL-1RA, IL-4, IL-5, IL-10 and IL-13) cytokines from blood and hematoma fluid samples were examined. Exploratory factor analysis indicated two major underlying immunological processes expressed by the cytokines in both blood and hematoma fluid, but with a different pattern and particularly regarding the cytokines IL-13, IL-6, IL-4 and TNF-α. Scores from confirmatory factor analysis models exhibited a higher correlation between pro- and anti-inflammatory activities in blood (r=0.98) than in hematoma fluid samples (r=0.92). However, correlations of inflammatory processes between blood and hematoma fluid samples were lower and non-significant. A structural equation model showed a significant association between increased anti-inflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH.
Although current recommendations suggest that hip hemiarthroplasties performed for femoral neck fractures be implanted with bone cement, it is known to cause cardiorespiratory and hemodynamic ...reactions that in some patients can be fatal. Older patients may be at particular risk of this complication, but because of its relative infrequency, large studies-perhaps even larger than can be achieved in the context of single-country national registries-are needed to get reasonably precise estimates as to its frequency. Pooling results from national registries reporting on death within 48 hours of cement exposure in this setting may therefore be helpful.
In a systematic review of studies based on large national registries, we asked: Does the risk of death within 48 hours of hip hemiarthroplasty differ between patients treated with cemented and cementless implants?
MEDLINE and Embase data sources were searched for cohort studies on patients with hip fractures treated with cement or cementless hip hemiprostheses based on results from national registries that tracked perioperative deaths within 48 hours of surgery, from 2010 or later (to include only studies that used contemporary cement techniques). We excluded registry research on elective THAs for other indications (such as degenerative joint disease), mixed populations (registries that combined patients having arthroplasty for fracture and for other diagnoses like osteoarthritis, such that we could not separate them), and overlapping data from the same registers (to avoid double and triple publications of similar data). Five studies met our inclusion criteria. The cohorts ranged from about 11,000 to about 25,000 patients. About 31% of the patients were in the cementless group. Two studies reported the age ranges of participating patients, and three studies communicated mean ages (which were 82 years for both sexes). Twice as many females as males were present in both the cemented and cementless group. When reported, more than 50% in both groups were in the American Society of Anesthesiologists physical status classification 3 or 4. Study quality was deemed good according to the Newcastle-Ottawa Scale. Publication bias was assessed using a funnel plot and the Egger test, and study heterogeneity was evaluated using the I2 heterogeneity statistic and Cochran Q heterogeneity test. There was some heterogeneity between the studies, with a Cochran Q statistics of 8.13 (degrees of freedom = 4; p = 0.08) and an I2 statistic of 50.8%. There was evidence for a small amount of publication bias (Egger test; p = 0.02). The pooled risk ratio (RR) from a random-effects model is presented with 95% confidence intervals. The primary endpoint was the occurrence of any fatalities within 48 hours of hip fracture treatment with cementless compared with cemented prostheses. We performed a sensitivity analysis to assess the needed association of a potential unmeasured or uncontrolled confounding, and we made an estimate of the amount of unmeasured confounding that would need to be present in order to change the direction of the result. We summarized this using a parameter known as the "E-value." Based on that sensitivity analysis, we found it unlikely that an unmeasured hypothetical confounder could explain the significant association between cemented and cementless implants and risk of death within 48 hours of hip hemiarthroplasty.
Compared with the cementless group, mortality was increased in the cemented group (RR 1.63 95% CI 1.31 to 2.02; p < 0.001). The number needed to harm from the pooled data was 1 of 183 operated patients; that is, for every 183 patients treated with cemented implants, one death would be expected.
Bone cement is associated with a higher risk of fatalities within 48 hours of surgery compared with cementless prostheses. However, numerous prior studies have found a higher risk of serious complications resulting in additional surgical procedures associated with cementless devices in this population; those complications, as well, may result in death. Based on our study alone, we cannot recommend cementless implants in this setting. Large, national registries should evaluate fixation choice in older patients with hip fractures, and those studies should consider both early death and the potential for later harms.
Level III, therapeutic study.
Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a ...cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.
Background:
Identification of factors predictive of outcome and change is important to improve treatment for patellofemoral pain (PFP). Few studies have examined the predictive value of psychological ...factors in PFP, although they have been reported to be important predictors in other musculoskeletal pain conditions.
Purpose:
To evaluate predictors of pain, function, and change 1 year after an exercise-based intervention in PFP.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
In sum, 112 patients were recruited to a randomized controlled trial; 98 attended 1-year follow-up. There were no between-group differences in the trial; thus, the material was analyzed as 1 cohort. Nine baseline factors—sex, bilateral pain, worst pain, pain duration, Anterior Knee Pain Scale (AKPS), kinesiophobia, anxiety and depression, self-efficacy, and number of pain sites throughout the body—were investigated for their predictive ability on outcome at 1 year (AKPS, worst pain) and for change at 1 year (global change score, change in AKPS, and change in worst pain). Multivariable linear regression models with stepwise backward removal method were used to find predictors of poor outcome.
Results:
Number of pain sites at baseline was a significant predictor of worse outcome for AKPS (B = −2.7; 95% CI, –4.0 to −1.3; P < .01), worst pain (B = 0.5; 95% CI, 0.2-0.8; P < .01), global change (B = −0.8; 95% CI, –1.2 to −0.5; P < .01), change in AKPS (B = −2.7; 95% CI, –4.0 to −1.3; P < .01), and change in worst pain (B = 0.5, 95% CI, 0.2-0.8; P < .01) at 1 year. Baseline scores for AKPS and worst pain predicted respective 1-year levels and change scores (P < .01). Lower self-efficacy and male sex predicted less global change (P < .01). Longer pain duration predicted final score and change score for worst pain (P < .01). The predictive models had reasonable fit with adjusted R2 from 0.22 to 0.35.
Conclusion:
Higher number of pain sites throughout the body was a consistent predictor of poor outcome and less change at 1 year. Baseline levels for AKPS and worst pain predicted respective final scores and change scores.
Registration:
NCT02114294 (ClinicalTrials.gov identifier).
To explore the long-term drug effectiveness and survival of reference rituximab (ref-RTX)-treated rheumatoid arthritis (RA) patients in an ordinary outpatient clinic. Second, we explored baseline ...predictors of drug effectiveness and survival, and third, we clarified reasons for stopping treatment. RA patients treated with ref-RTX between 2006 and 2020 in Norway were examined and monitored using recommended measures for disease activity and patient-reported outcomes (PROs). Drug effectiveness was assessed with random intercept linear mixed models; drug survival was assessed with Kaplan-Meier survival analysis. Reasons for discontinuation were ascertained. Baseline predictors of drug effectiveness and survival were estimated. Among 246 RA patients, at baseline, 17.1% were biologic disease-modifying anti-rheumatic drugs (bDMARDs) naïve, and 51.6% were currently using conventional synthetic DMARDs (csDMARDs). During the five-year follow-up, all disease activity and PRO measures improved significantly (p < 0.01), with more substantial changes noted in the second year. Drug survival was 83% after one year and declined to 34% after five years. The two most frequently reported reasons for discontinuation were the doctor's decision (36.2%) and lack or loss of effectiveness (19.2%). No significant difference was found between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs when analysing drug effectiveness and survival. Our real-life data show that ref-RTX-treated RA patients had satisfactory treatment responses; drug survival declined linearly over time. There was no significant difference between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs, both for drug effectiveness and survival.
Age-related changes and losses may lead to loneliness. However, some people do not become lonelier, even after negative life events. This study examines the development of loneliness based on ...Norwegian panel data (N = 2,315), age 40–80 years at baseline, and the impacts of partnership and health measured in 2002, 2007, and 2017. We ask: How does loneliness develop over time, and who resists becoming lonely? In the total group, loneliness decreased from 2002 to 2007 and then leveled off. In the eldest age group, 70–80 years at baseline, loneliness increased but only in the last period, from 2007 to 2017. In all age groups and at all three times, those who were not lonely more often had a partner and were more often in good health compared to those who were lonely. Period effects, cohort, and age-related changes influencing the development in loneliness over time are discussed.
PDF
