Different Subset Of Patients Research Articles

Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping.

A validation study of the high acuity readmission risk pediatric screen (HARRPS) tool©: Predicting readmission risk within the pediatric population

BackgroundThe initial research study of the High Acuity Readmission Risk Pediatric Screen (HARRPS) Tool © focused on using retrospective data to apply weighted values to the questions within the tool, identify overall risk score, and attribute risk categories (low, moderate, high risk) to the overall risk score. This study focused on validating the data from the initial study, as well as cross examining the need to include admission diagnosis within the tool. MethodStudy was a single-centered, retrospective chart review study using a different subset of patients from the initial study. Pediatric patients with thirty-day readmissions were compared to pediatric patients without a thirty-day readmission over a twelve-month period. Utilized same statistical software and methodology from initial study to identify if readmission risk probability could be replicated with a different population. ResultsThe initial study performed in 2018 demonstrated a c-statistic score/ area under the curve (AUC) of 0.68 [95% CI: 0.67, 0.69]. In addition, the initial study demonstrated as risk score increases, the probability of readmission gradually increased until a patient had a risk score of seven or greater, at which point readmission risk plateaued. This resulted in low, moderate, and high readmission risk categories. The current study performed using data from 2019 demonstrated an improved c-statistic score / AUC of 0.83 [95% CI: 0.80, 0.87] with admission diagnosis included, and a c-statistic score / AUC of 0.80 [95% CI: 0.76, 0.83] without the admission diagnosis included. The analysis of overall risk score demonstrated a substantial difference in how to interpret final readmission risk scores. Both the initial study and validation study were consistent in demonstrating a risk score of three or less was associated with low readmission risk. However, in the validation study, there was no substantial difference between moderate or high risk, leading to updating the tool from 3 risk categories into 2 risk categories of low risk and at risk of readmission. ConclusionBased on the finding from the validation study, the admission diagnosis was removed from the HARRPS Tool© as the difference in c-statistic score was nominal, and the risk categories were changed from three categories (low, moderate, high risk) to two categories of low risk (score 0–2) and at risk of readmission for a score of 3+. The ability of the HARRPS Tool© to predict readmission risk preforms best with a c-statistic = 0.80, outperforming the following tools: LACE (0.65), LACE -SDH (0.67), LACE + (0.61), Epic's readmission risk model (0.69), and SQLAPE ® (0.71) (Ryan, et al., 2021; Hwang, et al., 2021).

Graft Patency and Determinants of Outcome in Infrainguinal Bypasses - A Retrospective Study

Context: Chronic lower limb ischemia, an important marker of atherosclerosis, is a common clinical problem prevalent in all socioeconomic groups in our country and across the globe. Infrainguinal bypass is mandated in a subset of patients with critical limb ischemia to provide immediate limb salvage as well as excellent long-term results. Aim: The purpose of our retrospective study is to elucidate the effect of various known factors on the long term patency of infrainguinal bypass grafts performed in our patient population at a tertiary referral hospital. Methods: We retrospectively reviewed follow up data of 110 patients who had undergone infrainguinal bypass grafting over a period of ten years in our Institutional vascular registry. Graft patency rates and factors affecting thereof over this period were studied and the data statistically analysed. Overall cumulative patency rates were calculated by the life table survival method and compared with that of the patency rates of above-knee bypass procedures in the world literature. Patency rates in a different subset of patients were calculated and compared using the Wilcoxon (Gehan) test and Fisher's exact test to assess the influence of various factors in the long term outcome of the procedure. Results: Cumulative patency in terms of graft survival probabilities based on the life table analysis was 0.84, 0.80, and 0.64 at 30, 60, and 90 months respectively. Grafts in patients who had continued to smoke post-operatively had failed when compared with those who did not smoke (P = 0.01). Cumulative patency rates of non- diabetics were higher as compared to non-diabetics (0.70 vs 0.44; P = 0.04). Conclusion: Our study shows that continued smoking and diabetes are the determinant factors associated with graft occlusion. Strict avoidance of smoking and optimal control of diabetes is likely to improve graft function and long-term patency in patients undergoing infra-inguinal bypass grafting.

Outcomes of Anatomic Lung Resection for Cancer Are Better When Performed by Cardiothoracic Surgeons

Anatomic lung resection (ALR) outcomes are superior for cardiothoracic surgeons (CTSs) by analysis of Medicare; National Inpatient Sample; South Carolina Office of Research and Statistics; and Surveillance, Epidemiology, and End Results databases. Similar findings have been reported for all noncardiac thoracic procedures using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Our aim was to further delineate outcome differences between CTSs and general surgeons (GSs) specifically for ALR. A retrospective analysis of 15,574 nonemergent, nonpediatric ALR for lung cancer was conducted using the ACS-NSQIP 2013 to 2017 database. Included procedures were all ALR for lung cancer. Surgeons were classified as CTSs or GSs. Other specialties were excluded. Preoperative characteristics and 30-day outcomes were compared by bivariate (chi-square test) and multivariate analysis. Multivariate analysis was conducted by multiple logistic regression. CTSs performed 14,172 (91.0%) of included procedures, and GSs performed 1402 (9.0%). A thoracoscopic approach was utilized at a similar rate (49.08% for CTSs vs 49.71% for GSs; P= .747). The extent of resection differed in a statistically, but not clinically, significant fashion. CTS patients had a higher rate of preoperative dyspnea (22.66% for CTSs vs 17.62% for GSs; P< .001). Procedures performed by CTSs had a lower risk-adjusted odds ratio of overall morbidity, pulmonary morbidity, sepsis or septic shock, bleeding requiring transfusion, and length of stay greater than the median (5 days). ALR outcomes are superior for CTSs when compared with GSs. This is consistent with prior studies looking at this specific subset of patients and studies looking at a different subset of patients using the ACS-NSQIP database.

Effect of hepatogenous jaundice on liver stiffness measurement in patients with chronic hepatitis B

Objective To evaluate the impact of intrahepatic cholestasis on liver stiffness measurement(LSM) of two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B. Methods Between June 2011 and December 2016, total of 1 188 patients with chronic hepatitis B infection were enrolled to collect clinical, 2D-SWE, biochemical variables and histological (METAVIR scoring system) datas. LSM was compared between normal total bilirubin group(TB<23.9 μmol/L) versus abnormal TB group(≥23.9 μmol/L). Correlation of TB with LSMs was assessed. Results Nine hundred and seventy-three patients with effective LSM in the study were analyzed. Within the same fibrosis stage (F1-F4), LSM showed significantly higher value in abnormal TB group than those of normal TB group (r=0.328, 0.247, 0.495, 0.435, all P<0.001). Increased LSM for abnormal TB group was generally found within different subset of patients[fibrosis stage≤F2, ALT≥2×upper limit of normal (ULN); fibrosis stage≤F2, METAVIR activity grade ≤A1 or ≥A2], with r=0.266, 0.210, 0.243 (all P<0.001), respectively.Increased LSM for abnormal TB group was also found within different subset of patients [fibrosis stage≥F3, ALT<2×ULN, ≥2×ULN; fibrosis stage≥F3, METAVIR activity grade≥A2, with r=0.671, 0.200, 0.468 (all P<0.05)]. Conclusions Hepatogenous jaundice induced to intrahepatic cholestasis shows slight positive correlation with LSMs in patients with chronic hepatitis B. Key words: Shear wave elastography; Jaundice, hepatogenous; Hepatitis B; Elastic modulus

Counter-regulation of regulatory T cells by autoreactive CD8+ T cells in rheumatoid arthritis

The mechanisms whereby autoreactive T cells escape peripheral tolerance establishing thus autoimmune diseases in humans remain an unresolved question. Here, we demonstrate that autoreactive polyfunctional CD8+ T cells recognizing self-antigens (i.e., vimentin, actin cytoplasmic 1, or non-muscle myosin heavy chain 9 epitopes) with high avidity, counter-regulate Tregs by killing them, in a consistent percentage of rheumatoid arthritis (RA) patients. Indeed, these CD8+ T cells express a phenotype and gene profile of effector (eff) cells and, upon antigen-specific activation, kill Tregs indirectly in an NKG2D-dependent bystander fashion in vitro. This data provides a mechanistic basis for the finding showing that AE-specific (CD107a+) CD8+ T killer cells correlate, directly with the disease activity score, and inversely with the percentage of activated Tregs, in both steady state and follow-up studies in vivo. In addition, multiplex immunofluorescence imaging analyses of inflamed synovial tissues in vivo show that a remarkable number of CD8+ T cells express granzyme-B and selectively contact FOXP3+ Tregs, some of which are in an apoptotic state, validating hence the possibility that CD8+ Teff cells can counteract neighboring Tregs within inflamed tissues, by killing them. Alternatively, the disease activity score of a different subset of patients is correlated with the expansion of a peculiar subpopulation of autoreactive low avidity, partially-activated (pa)CD8+ T cells that, despite they conserve the conventional naïve (N) phenotype, produce high levels of tumor necrosis factor (TNF)-α and exhibit a gene expression signature of a progressive activation state. Tregs directly correlate with the expansion of this autoreactive (low avidity) paCD8+ TN cell subset in vivo, and efficiently control their differentiation rather their proliferation in vitro. Interestingly, autoreactive high avidity CD8+ Teff cells or low avidity paCD8+ TN cells are significantly expanded in RA patients who would become non-responders or patients who would become responders to TNF-α inhibitor therapy, respectively. These data provide evidence of a previously undescribed role of such mechanisms in the progression and therapy of RA.

Towards an overarching model for electronic medical-record systems, including problem-oriented, goal-oriented, and other approaches

There is no consensus among health professionals on how to structure medical records to serve clinical decision-making. Three approaches co-exist (source-oriented, problem-oriented, goal-oriented), each suiting a different subset of patients. In primary care, the problem-oriented approach is dominant, but for patients with multiple conditions (multimorbidity) the goal-oriented approach seems more appropriate. There is a need to combine different approaches in one medical-record system. In this article, we explain some misconceptions about ‘problems’ and ‘goals’ that hinder the way to consensus. When putting the approaches into historical perspective, it becomes evident that each relates to a different definition of health. Each approach has its specific merits that should be preserved even when health definitions change. Hence, we combine the merits of each approach into one overarching model, as to show the way to a new generation of electronic medical-record systems that can serve all patients. This model has three levels: a level of problems, diseases, and patient goals, a level of (shared) objectives, and a level of action plans and results.

Using Ventilator-Associated Pneumonia Rates as a Health Care Quality Indicator: A Contentious Concept.

Pneumonia is a leading cause of hospital-acquired infections, although reported rates of ventilator-associated pneumonia (VAP) have been declining in recent years. A multifaceted infection prevention approach, using a “ventilator bundle,” has been shown to reduce the frequency of VAP, while improving other patient outcomes. Because of difficulties in defining VAP, the Center for Medicare and Medicaid Service introduced a new streamlined ventilator-associated event (VAE) definition in 2013 for the surveillance of complications in mechanically ventilated patients. VAE measures are increasingly being measured by institutions in the United States in place of VAP rates and as a potential measure of the quality of intensive care unit (ICU) care. However, there is increased recognition that the streamlined definitions identify a different subset of patients than those identified by traditional VAP surveillance and that VAP prevention strategies may not impact all the causes of VAE. Also, VAP and VAE rates may not always reflect the quality of care in a given ICU, especially since patient factors, beyond the control of the hospital, may impact the rates of VAP and VAE. In this review, we discuss the issues related to VAP as a quality measure and the areas of uncertainty related to the new VAE definitions.

Androgen-deprivation therapy plus docetaxel-based chemotherapy in metastatic hormone-sensitive prostate cancer. A meta-analysis of randomized clinical trials.

188 Background: Androgen-deprivation therapy (ADT) is the standard of treatment for patients with newly diagnosed metastatic prostatic cancer. Nevertheless, recent trials have suggested a role for chemotherapy in these patients. We performed a systematic review and meta-analysis to assess the efficacy and safety of docetaxel-based chemotherapy in combination with ADT for patients with hormone-sensitive metastatic prostate cancer. Methods: Randomized clinical trials (RCT) were identified after systematic searching of electronic databases (MEDLINE, OVID and The Cochrane Central Register of Controlled Trials), as well as ASCO conference proceedings from 2010 to 2015. We included only RCT comparing ADT versus the combination of ADT plus docetaxel-based chemotherapy in patients with newly diagnosed metastatic prostate cancer. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes: overall survival (OS) and clinical progression-free survival (PFS), according to the inverse-variance method. Heterogeneity was measured using the Q and I2statistics. Results: Three RCT (n = 2 262), were included in our meta-analysis (E3805, GETUG-AFU 15 and the M1 subgroup from STAMPEDE Trial). Docetaxel-based chemotherapy plus ADT was associated with improved OS (HR: 0.74; 95% CI: 0.60-0.90; p = 0.003). The heterogeneity of these trials was moderate (Tau2: 0.02; I2: 51%; p = 0.13). Clinical PFS was also significantly better in patients receiving docetaxel-based chemotherapy (HR: 0.67; 95% CI 0.55-0.82; p = 0.0001), with moderate between-study heterogeneity detected (Tau2: 0.01; I2: 42%; p = 0.19). Different subset of patients in these trials can explain the aforementioned heterogeneity. Regarding adverse drug reactions grade 3 or higher, neutropenia was reported in a range from 36% in the GETUG-AFU 15 Trial to 12% in the STAMPEDE trial and febrile neutropenia was reported from 6.1% in the E3805 Trial to 12% in the STAMPEDE Trial. Conclusions: The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS. New trials are needed to determine which patients benefit the most from this intervention.

Assessment of a scoring system for Basal Cell Carcinoma with multi-beam optical coherence tomography.

Multi-beam optical coherence tomography (OCT) is a novel method of non-invasive skin imaging allowing the evaluation of tissue at high level of lateral and axial resolution. It permits the horizontal and vertical evaluation of the extent of diseases. Herein, we aimed to validate diagnosing basal cell carcinoma (BCC) by OCT using a newly developed scoring system ('Berlin Score'-BS). This was based on the predetermined criteria such as dark border underneath the tumour and ovoid structures. Their frequency and distribution in subtypes of BCC were evaluated. The study was conducted in two phases, in which the experience of examiner differed. A total of 127 BCC and 50 other skin diseases were examined. In phase one, students performed the evaluation of skin lesions using the BS, while in phase two an expert performed the scoring in a different subset of patients. Application of BS by students revealed sensitivity and specificity of 92.8% (95% CI 85.4-96.8) and 24.1% (95% CI 11.0-43.4) when reaching the lower threshold BS≥8. The most common BCC subtypes were superficial (28.7%) and nodular (22.6%) BCC. Second phase was carried out to verify collected data by a dermatological specialist and expert in using OCT. Increased sensitivity and specificity for OCT amounted to 96.6% (95% CI 80.4-99.8) and 75.2% (95% CI 52.5-90.9). Thereby 88% of all diagnoses were correctly classified confirmed by histopathology. Multi-beam optical coherence tomography revealed to be a fast and promising device for assessing lesions by means of BS. Both students, who benefit from practice in handling OCT, and experts are able to perform this procedure. However, experience and training in the interpretation markedly increased sensitivity and specificity of the BS in our study. Moreover, redefinition and refining of the criteria seems necessary and may further increase the diagnostic value of OCT for NMSC.

Early NK Cell Proliferation After Umbilical Cord Blood Transplantation Is Associated With Superior Disease-Free Survival Due To Reduced Leukemia Relapse

Compared to traditional chemotherapy, allogeneic hematopoietic cell transplantation (allo-HCT) has the potential of triggering graft vs. leukemia (GVL) reactions that make this procedure uniquely curative. Despite this, relapse remains the most common cause of treatment failure. Early after allo-HCT the donor immune system reconstitutes within the host and natural killer (NK) cells are the earliest lymphocyte population to recover. Previous studies by us and other investigators have linked rapid lymphocyte recovery and/or high NK cell numbers early after transplant with less relapse. Mechanistically, the reasons for this are unknown. We hypothesized that NK cell proliferation would be associated with allo-HCT outcomes. In a large data set with short-term follow-up we compared stem cell source to NK cell proliferation at Day 28 after transplantation (using Ki67+ staining). In patients undergoing autologous (n=117), sibling (n=57), single umbilical cord blood (sUCB) (n=62) or double umbilical cord blood (dUCB) (n=50) transplantation there were significant differences in the median NK cell proliferation (2.1%, 3.3%, 3.8%, and 19.2%, respectively, p&lt;0.0001). These results suggest that NK cell proliferation is increased when patients are transplanted with stem cell sources that have an increased number of HLA mismatches (dUCB). We next examined factors extrinsic to the NK cells to determine whether differences in the four patient groups were due to these factors. Regulatory T cells (Tregs) are known to negatively regulate the proliferation and activation of a variety of cell types, including NK cells. We utilized the percentage and absolute number of Tregs (defined as CD4+CD25highFoxP3+CD127low) at Day 28 (available for a subset of the above patient samples) and correlated it with the percentage of proliferating NK cells at Day 28 after allogeneic transplant (n=212). The median percentage of Tregs within the lymphocyte fraction was 1.49%. In patients with higher than 1.49% Tregs, the mean NK cell proliferation was 10.8% +/-16.4. In contrast, patients with lower than 1.49% Tregs had a mean NK cell proliferation of 21.2% +/-24.3 (p=0.0004). A nearly identical trend was observed for the absolute numbers of Tregs, suggesting that Tregs may play an extrinsic role in NK cell proliferation after allo-HCT. To further address differences in lymphocyte proliferation and clinical outcomes, we used Ki67 staining to assess T cell (CD4+ and CD8+) and NK cell (CD3-CD56+) proliferation at Day 28 in a different subset of patients undergoing dUCB transplant with acute leukemia or MDS (80%) or other malignant disorders using either myeloablative (42%) or reduced intensity conditioning (58%) and a median of one year follow-up (n=53). There was no association of transplant outcomes with T cell (CD4 or CD8) proliferation. In the NK cell compartment there was a wide range in the percentage of proliferating NK cells (0-86%), with a median of 20%. Patients were segregated into high (&gt;20%) and low (&lt;20%) NK cell proliferating groups and assessed for cytokine levels and transplant outcomes. At Day 28 soluble IL15 levels were not different between high and low NK cell proliferating patients. There was no significant association between NK cell proliferation and the probability or time to neutrophil recovery (p=0.15) or treatment related mortality (p=0.88). Excluding the 14 patients who developed aGVHD prior to day of NK cell assessment (Day 28), the high NK proliferating group had a trend toward a higher cumulative incidence of aGVHD (46% vs. 25%, p=0.17). Using multivariable analysis to control for a variety of patient and disease-associated variables, patients with high NK cell proliferation had significantly better disease-free survival (HR=0.29, 95%CI=0.12-0.71, p=0.01) (Figure 1). Strikingly, patients with high NK cell proliferation were 4-times less likely to relapse (HR=0.24, 95%CI=0.08-0.77, p=0.02). Collectively, these studies show that early NK cell proliferation is associated with superior outcomes after dUCB transplantation, due to reduced relapse, and that this is partly modulated by Tregs. Prospective strategies to increase NK cell proliferation may be of therapeutic benefit to improve transplant outcomes.Figure 1Disease Free Survival for patients undergoing dUCB transplant (n=53) based on low (blue) vs high (red) NK cell proliferation at Day 28 post transplant.Figure 1. Disease Free Survival for patients undergoing dUCB transplant (n=53) based on low (blue) vs high (red) NK cell proliferation at Day 28 post transplant. Disclosures: Wagner: Novartis: Research Funding. Miller:Coronado Biosciences: Scientific Advisory Board Other.

Peri‐operative oxygen use – the anaesthetist's perspective

The recent editorial by Decalmer & O'Driscoll 1 raised several issues that merit discussion. A significant proportion of the editorial presents data from studies reporting the harmful effects of excess oxygen. Although now accepted that careful titration of oxygen therapy in certain groups of patients can improve outcome, they represent a very different sub-set of patients to the majority undergoing anaesthesia and surgery. Therefore, the comparisons drawn may not be valid. No evidence is presented to support the claim that supplementary oxygen is likely to be of no benefit for the majority of patients in the immediate postoperative period. Furthermore, it is unknown whether avoiding supplementary oxygen at this time would actually lead to an increase in adverse events and patient harm. The 4th National Audit Project (NAP4) 2 and Difficult Airway Society guidelines 3 both highlight the potential for airway and breathing problems during the ‘immediate postoperative period’. Anaesthetists rely on an oxygen-rich functional residual capacity to allow time to deal safely with such problems. Doubtless, many patients' lives have been saved in this way. In addition, during this period, supplementary oxygen can be vital in preventing hypoxaemia due to hypoventilation induced by the respiratory depressant effects of anaesthetic drugs. In-line with the British Thoracic Society (BTS) guidelines 4, Decalmer & O'Driscoll's editorial focuses predominantly on targeting peripheral oxygen saturations (SpO2). This fails to highlight the importance of patient assessment in the postoperative period to determine the cause of hypoxaemia and commence appropriate treatment. A postoperative patient with a SpO2 of 94% would be acceptable according to BTS guidelines, but if this requires a FIO2 of 60% further assessment and intervention are required. Furthermore, if this patient has a haemoglobin of 6.0 g.dl−1, a SpO2 of 94% probably represents inadequate tissue oxygen delivery, which should be corrected by red cell transfusion. The editorial gives the impression that many postoperative patients are being harmed through excessive use of oxygen and that the focus should be on targeting SpO2. I do not believe that this is evidence-based.

Can Point-of-Care Urine LAM Strip Testing for Tuberculosis Add Value to Clinical Decision Making in Hospitalised HIV-Infected Persons?

BackgroundThe urine lipoarabinomannan (LAM) strip-test (Determine®-TB) can rapidly rule-in TB in HIV-infected persons with advanced immunosuppression. However, given high rates of empiric treatment amongst hospitalised patients in high-burden settings (∼50%) it is unclear whether LAM can add any value to clinical decision making, or identify a subset of patients with unfavourable outcomes that would otherwise have been missed by empiric treatment.Methods281 HIV-infected hospitalised patients with suspected TB received urine LAM strip testing, and were categorised as definite (culture-positive), probable-, or non-TB. Both the proportion and morbidity of TB cases identified by LAM testing, early empiric treatment (initiated prior to test result availability) and a set of clinical predictors were compared across groups.Results187/281 patients had either definite- (n = 116) or probable-TB (n = 71). As a rule-in test for definite and probable-TB, LAM identified a similar proportion of TB cases compared to early empiric treatment (85/187 vs. 93/187, p = 0.4), but a greater proportion than classified by a set of clinical predictors alone (19/187; p<0.001). Thirty-nine of the 187 (21%) LAM-positive patients who had either definite- or probable-TB were missed by early empiric treatment, and of these 25/39 (64%) would also have been missed by smear microscopy. Thus, 25/187 (8%) of definite- or probable-TB patients with otherwise delayed initiation of TB treatment could be detected by the LAM strip test. LAM-positive patients missed by early empiric treatment had a lower median CD4 count (p = 0.008), a higher median illness severity score (p = 0.001) and increased urea levels (p = 0.002) compared to LAM-negative patients given early empiric treatment.ConclusionsLAM strip testing outperformed TB diagnosis based on clinical criteria but in day-to-day practice identified a similar proportion of patients compared to early empiric treatment. However, compared to empiric treatment, LAM identified a different subset of patients with more advanced immunosuppression and greater disease severity.

Data mining in the Life Sciences with Random Forest: a walk in the park or lost in the jungle?

In the Life Sciences ‘omics’ data is increasingly generated by different high-throughput technologies. Often only the integration of these data allows uncovering biological insights that can be experimentally validated or mechanistically modelled, i.e. sophisticated computational approaches are required to extract the complex non-linear trends present in omics data. Classification techniques allow training a model based on variables (e.g. SNPs in genetic association studies) to separate different classes (e.g. healthy subjects versus patients). Random Forest (RF) is a versatile classification algorithm suited for the analysis of these large data sets. In the Life Sciences, RF is popular because RF classification models have a high-prediction accuracy and provide information on importance of variables for classification. For omics data, variables or conditional relations between variables are typically important for a subset of samples of the same class. For example: within a class of cancer patients certain SNP combinations may be important for a subset of patients that have a specific subtype of cancer, but not important for a different subset of patients. These conditional relationships can in principle be uncovered from the data with RF as these are implicitly taken into account by the algorithm during the creation of the classification model. This review details some of the to the best of our knowledge rarely or never used RF properties that allow maximizing the biological insights that can be extracted from complex omics data sets using RF.

Tertiary Pediatric Emergency Department Admission Rates Fall as Waiting Times Increase

To examine whether children in the same triage category presenting to a tertiary paediatric emergency department are more likely to be admitted to hospital if their wait is longer. Retrospectively during a 7-year period, we determined the admission rate of children with lower acuity triage scores and compared 3 groups; those seen in their recommended triage time (group A), those seen under twice their recommended time (group B), and those seen in over twice their recommended time (group C). Patients in groups B and C were less likely to be admitted for both triage categories 3 and 4 compared with group A (P < 0.005 for all admission rate comparisons). This held true in individual diagnostic groups. Predictably, but reassuringly, those patients waiting longer than the recommended category time are no more likely to get admitted and do not represent a grossly different subset of patients in terms of age and diagnosis. Further work is needed to identify, at the point of triage, the characteristics of children who are unlikely to deteriorate during their wait.

Older adolescents and young adults with cancer: a different subset of patients?

Older adolescents and young adults with cancer: a different subset of patients?

The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer

Objective. To evaluate the effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. Methods. All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington between January 1990 and January 2000 were eligible; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). Results. Age was <45 years in 15% of patients, between 46 and 64 years in 47% of patients, and >65 years in 38% of patients. Younger patients were statistically more obese than older patients (Body Mass Index of 40.3 kg/m 2 vs. 35.3 kg/m 2 vs. 31.0 kg/m 2, P < 0.001). Intraoperatively, there were no differences between the three groups in the percentage of patients with lymph node sampling, operative time, blood loss, or complications. Postoperatively, older patients had more wound infections ( P = 0.002), more cardiac events ( P = 0.001), and more episodes of ileus ( P = 0.025). Evaluation of pathology revealed that patients <45 years old were statistically more likely to have endometrioid histology, grade I tumors, and stage IA disease. Women over age 65 were significantly more likely to have papillary serous histology, grade 3 tumors, and stage IC as compared to the younger patients. A subset analysis of patients >75 years of age showed an increase in the percentage of patients with papillary serous histology (22% vs. 3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease (21% vs. 3%, P = 0.001) when compared to patients <45 years old. Evaluation of endometrioid tumors only revealed a similar pattern of deeper myometrial invasion and higher tumor grade as age increased. Conclusions. Younger patients with endometrial cancer are generally more obese, with lower grade, lower stage disease, and with more favorable histologic cell types. Despite this, approximately a quarter have stage II–IV disease and 9% have positive lymph nodes. The older patients represent a dramatically different subset of patients. They are more likely to have aggressive papillary serous histology, higher grade tumors, and advanced stage disease. Age should be a consideration in appropriate referrals to gynecologic oncologists.

Rate control in atrial fibrillation: choice of treatment and assessment of efficacy.

The clinical relevance and high social costs of atrial fibrillation have boosted interest in rate control as a cost-effective alternative to long-term maintenance of sinus rhythm (i.e. rhythm control). Prospective studies show that rate control (coupled with thromboembolic prophylaxis) is a valuable treatment option for all forms of atrial fibrillation. The rationale for rate control is that high ventricular rates, frequently found in atrial fibrillation, lead to haemodynamic impairment, consisting of a variable combination of loss of atrial kick, irregularity in ventricular response and inappropriately rapid ventricular rate, depending on the type of underlying heart disease. Long-term persistence of tachycardia at a high ventricular rate can lead to various degrees of ventricular dysfunction and even to tachycardiomyopathy-related heart failure. Identification of this reversible and often concealed form of left ventricular dysfunction can permit effective management by rate (or rhythm) control. Although acute rate control (to reduce ventricular rate within hours) is still often based on digoxin administration, for patients without left ventricular dysfunction, calcium channel antagonists or beta-adrenoceptor antagonists (beta-blockers) are generally more appropriate and effective. In chronic atrial fibrillation, long-term rate control (to reduce morbidity/mortality and improve quality of life) must be adapted to patients' individual characteristics to grant control during daily activities, including exercise. According to current guidelines, the clinical target of rate control should be a ventricular rate below 80-90 bpm at rest. However, in many patients, assessment of the appropriateness of different drugs should include exercise testing and 24h-Holter monitoring, for which specific guidelines are needed. In practice, rate control is considered a valid alternative to rhythm control. Recent prospective trials (e.g. the Pharmacological Intervention in Atrial Fibrillation [PIAF] and the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] trials) have shown that in selected patients, rate control provides similar benefits, more economically, in terms of quality of life and long-term mortality. The choice of a rate control medication (digoxin, beta-blockers, calcium channel antagonists or possibly amiodarone) or a non-pharmacological approach (mainly atrioventricular node ablation coupled with pacing) must currently be based on clinical assessment, which includes assessing the presence of underlying heart disease and haemodynamic impairment. Definite guidelines are required for each different subset of patients. Rate control is particularly tricky in patients with heart failure, for whom non-pharmacological options can also be considered. The preferred pharmacological options are beta-blockers for stabilised heart failure and digoxin for unstabilised forms.