How do validated measures of functional outcome compare with commonly used outcomes in administrative database research for lumbar spinal surgery?

Clinical interpretation of health services research based on administrative databases is limited by the lack of patient-reported functional outcome measures. Reoperation, as a surrogate measure for poor outcome, may be biased by preferences of patients and surgeons and may even be planned a priori. Other available administrative data outcomes, such as postoperative cross sectional imaging (PCSI), may better reflect changes in functional outcome. The purpose was to determine if postoperative events captured from administrative databases, namely reoperation and PCSI, reflect outcomes as derived by validated functional outcome measures (short form 36 scores, Oswestry disability index) for patients who underwent discretionary surgery for specific degenerative conditions of the lumbar spine such as disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis. After reviewing the records of all patients surgically treated for disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis at our institution, we recorded the occurrence of PCSI (MRI or CT-myelograms) and reoperations, as well as demographic, surgical, and functional outcome data. We determined how early (within 6 months) and intermediate (within 18 months) term events (PCSI and reoperations) were associated with changes in intermediate (minimum 1 year) and late (minimum 2 years) term functional outcome, respectively. We further evaluated how early (6–12 months) and intermediate (12–24 months) term changes in functional outcome were associated with the subsequent occurrence of intermediate (12–24 months) and late (beyond 24 months) term adverse events, respectively. From 148 surgically treated patients, we found no significant relationship between the occurrence of PCSI or reoperation and subsequent changes in functional outcome at intermediate or late term. Similarly, earlier changes in functional outcome did not have any significant relationship with subsequent occurrences of adverse events at intermediate or late term. Although it may be tempting to consider administrative database outcome measures as proxies for poor functional outcome, we cannot conclude that a significant relationship exists between the occurrence of PCSI or reoperation and changes in functional outcome

Fast-TIPL Occurs for Salient Images without a Memorization Requirement in Men but Not in Women

Recent research of task-irrelevant perceptual learning (TIPL) demonstrates that stimuli that are consistently presented at relevant point in times (e.g. with task-targets or rewards) are learned, even in the absence of attention to these stimuli. However, different research paradigms have observed different results for how salient stimuli are learned; with some studies showing no learning, some studies showing positive learning and others showing negative learning effects. In this paper we focused on how the level of processing of stimuli impacts fast-TIPL. We conducted three different experiments in which the level of processing of the information paired with a target was manipulated. Our results indicated that fast-TIPL occurs when participants have to memorize the information presented with the target, but also when they just have to process this information for a secondary task without an explicit memorization of those stimuli. However, fast-TIPL does not occur when participants have to ignore the target-paired information. This observation is consistent with recent models of TIPL that suggest that attentional signals can either enhance or suppress learning depending on whether those stimuli are distracting or not to the subjects' objectives. Our results also revealed a robust gender effect in fast-TIPL, where male subjects consistently show fast-TIPL, whereas the observation of fast-TIPL is inconsistent in female subjects

WHO-defined ‘myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations

The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with ‘myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age ⩾70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or ⩾2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations

Alpha-Toxin Induces Programmed Cell Death of Human T cells, B cells, and Monocytes during USA300 Infection

This investigation examines the influence of alpha-toxin (Hla) during USA300 infection of human leukocytes. Survival of an USA300 isogenic deletion mutant of hla (USA300Δhla) in human blood was comparable to the parental wild-type strain and polymorphonuclear leukocyte (PMN) plasma membrane permeability caused by USA300 did not require Hla. Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) following infection by USA300, USA300Δhla, and USA300Δhla transformed with a plasmid over-expressing Hla (USA300Δhla Comp) demonstrated this toxin plays a significant role inducing plasma membrane permeability of CD14+, CD3+, and CD19+ PBMCs. Rapid plasma membrane permeability independent of Hla was observed for PMNs, CD14+ and CD19+ PBMCs following intoxication with USA300 supernatant while the majority of CD3+ PBMC plasma membrane permeability induced by USA300 required Hla. Addition of recombinant Hla to USA300Δhla supernatant rescued CD3+ and CD19+ PBMC plasma membrane permeability generated by USA300 supernatant. An observed delay in plasma membrane permeability caused by Hla in conjunction with Annexin V binding and ApoBrdU Tunel assays examining PBMCs intoxicated with recombinant Hla or infected with USA300, USA300Δhla, USA300Δhla Comp, and USA300ΔsaeR/S suggest Hla induces programmed cell death of monocytes, B cells, and T cells that results in plasma membrane permeability. Together these findings underscore the importance of Hla during S. aureus infection of human tissue and specifically demonstrate Hla activity during USA300 infection triggers programmed cell death of human monocytes, T cells and B cells that leads to plasma membrane permeability

Progression to AIDS in South Africa Is Associated with both Reverting and Compensatory Viral Mutations

We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775). Immune responses were measured by γ-interferon ELISPOT assays. HLA-associated viral polymorphisms were determined using phylogenetically corrected techniques, and viral replication capacity (VRC) was measured by comparing the growth rate of gag-protease recombinant viruses against recombinant NL4-3 viruses. We report that in advanced disease (CD4 counts <100 cells/µl), T cell responses narrow, with a relative decline in Gag-directed responses (p<0.0001). This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of “immune relaxation”. The median VRC from patients with CD4 counts <100 cells/µl was higher than from patients with CD4 counts ≥500 cells/µl (91.15% versus 85.19%, p = 0.0004), potentially explaining the rise in viral load associated with disease progression. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). These data provide novel insights into the mechanisms of HIV disease progression in South Africa. Restoration of fitness correlates with loss of viral control in late disease, with evidence for both preserved and relaxed selection pressure across the HIV genome. Interventions that maintain viral fitness costs could potentially slow progression

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study

Background:Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages.Objective:To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI.Methods:Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years.Results:Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher.Conclusions:Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring

Act first, think later: the presence and absence of inferential planning in problem solving.

Planning is fundamental to successful problem solving, yet individuals sometimes fail to plan even one step ahead when it lies within their competence to do so. In this article, we report two experiments in which we explored variants of a ball-weighing puzzle, a problem that has only two steps, yet nonetheless yields performance consistent with a failure to plan. The results fit a computational model in which a solver's attempts are determined by two heuristics: maximization of the apparent progress made toward the problem goal and minimization of the problem space in which attempts are sought. The effectiveness of these heuristics was determined by lookahead, defined operationally as the number of steps evaluated in a planned move. Where move outcomes cannot be visualized but must be inferred, planning is constrained to the point where some individuals apply zero lookahead, which with n-ball problems yields seemingly irrational unequal weighs. Applying general-purpose heuristics with or without lookahead accounts for a range of rational and irrational phenomena found with insight and noninsight problems

Pregnancy and child health outcomes in pediatric and young adult leukemia and lymphoma survivors: a systematic review

As long-term survival is high for children and young adults diagnosed with leukemia and lymphoma, delineating maternal, fetal and offspring health risks is important to their family planning. This systematic review examined data comparing these health risks between leukemia and lymphoma survivors and women without a history of cancer. Following a search of Embase, PubMed, CINAHL, Cochrane, and Web of Science, 142 articles were screened and 18 were included in this review. No higher risks of spontaneous abortion, maternal diabetes and anemia, stillbirth, birth defects, or childhood cancer in offspring were observed in survivors compared to controls. Important to counseling and clinical care, live birth rates were lower, while preterm birth and low birth weight risks were modestly higher in survivors compared to controls. Findings were largely reassuring but highlight the lack of data on maternal cardiopulmonary risks, differential risk by cancer treatment type, and interventions to decrease these risks