Effects of knee compartment, concomitant surgery and smoking on medium-term outcome of microfracture

PurposeThe aim of this study was to determine the effect of compartment location, concomitant arthroscopic surgery and smoking on the medium-term outcome of knee microfracture.MethodsFrom a database of all 396 patients treated with microfracture for cartilage lesions in our Unit, details were taken of the 316 patients who met our inclusion criteria. Outcome was assessed by a self-administered postal questionnaire containing a general satisfaction question and a battery of four functional assessment scores. The rank sum of the four assessment scores was used as a single global functional outcome.ResultsAfter two rounds of questionnaires 196 patients responded. Their average follow up was 37 months. In all, 72% of the patients were satisfied with their outcome and 19% were not. Patients with an affected lateral or patellofemoral compartment improved 1.5 SD, significantly more than those with an affected medial compartment who improved 1 SD. However, their satisfaction rates did not differ significantly. Having concomitant knee surgery did not significantly affect the functional outcome or satisfaction rate. Significantly fewer smokers than non-smokers were satisfied (54 vs 76%) and more dissatisfied (34 vs 15%), but differences in functional outcome were small and non-significant.ConclusionsPatients with a lesion in the patellofemoral or lateral compartment have a significantly larger improvement than those with a medial compartment lesion. Satisfaction rates among these patients groups are however similar. Having concomitant arthroscopic knee surgery, in particular partial meniscectomies and ACL reconstruction, hardly affects the outcome of microfracture. Smoking is associated with a lower satisfaction rate although it has only a small effect on functional outcome. Finally, younger patients fare better than older patients although a cut-off point is hard to define. This information should help surgeons counsel patients better regarding prognosis and expectations after surgery.     

High-sensitivity tandem mass spectrometry assay for serum estrone and estradiol

High-sensitivity measurement of serum estrogens is important in adult and pediatric endocrinology and oncology. We developed a high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of estrone (E1) and estradiol (E2). Aliquots of 200 muL of serum were spiked with internal standard, extracted, derivatized with dansyl chloride, and analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total imprecision for the method was less than 11%; the limit of quantitation was 1 pg/mL. Reference intervals were established with samples from more than 900 healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens in children reached adult levels by Tanner stage 3. In men and postmenopausal women, the median concentrations of total estrogens (E1 + E2) were 39 and 22 pg/mL, and the median E2/E1 ratios were 0.98 and 0.55, respectively. The method requires a small sample volume and has adequate sensitivity and specificity for analyzing estrogens in samples from postmenopausal women, men, and children.     

Auditory evoked fields predict language ability and impairment in children.

Recent evidence suggests that a subgroup of children with autism show similarities to children with Specific Language Impairment (SLI) in the pattern of their linguistic impairments, but the source of this overlap is unclear. We examined the ability of auditory evoked magnetic fields to predict language and other developmental abilities in children and adolescents. Following standardized assessment of language ability, nonverbal IQ, and autism-associated behaviors, 110 trails of a tone were binaurally presented to 45 7-18 year olds who had typical development, autism (with LI), Asperger Syndrome (i.e., without LI), or SLI. Using a 151-channel MEG system, latency of left hemisphere (LH) and right hemisphere (RH) auditory M50 and M100 peaks was recorded. RH M50 latency (and to a lesser extent, RH M100 latency) predicted overall oral language ability, accounting for 36% of the variance. Nonverbal IQ and autism behavior ratings were not predicted by any of the evoked fields. Latency of the RH M50 was the best predictor of clinical LI (i.e., irrespective of autism diagnosis), and demonstrated 82% accuracy in predicting Receptive LI; a cutoff of 84.6 ms achieved 92% specificity and 70% sensitivity in classifying children with and without Receptive LI. Auditory evoked responses appear to reflect language functioning and impairment rather than non-specific brain (dys)function (e.g., IQ, behavior). RH M50 latency proved to be a relatively useful indicator of impaired language comprehension, suggesting that delayed auditory perceptual processing in the RH may be a key neural dysfunction underlying the overlap between subgroups of children with autism and SLI.     

Classification of normal and pathological tremors using a multidimensional electromagnetic system

A new multidimensional movement analysis system was used to record limb tremor over six degrees-of-freedom, and signal processing techniques were explored to develop a suitable classification method to distinguish between different types of tremor. The specific aims were to investigate the ability of the system to screen for differences between normal subjects and a group of neurological patients, and then to differentiate between three diagnostic groups of patients.

Postural tremor at the hand was recorded in normal subjects (n=24) and patients with essential tremor (n=21), multiple sclerosis (n=17) and parkinsonism (n=19). Data were collected using a 3Space Fastrak^® (Polhemus, Inc.) over six degrees-of-freedom (three translational directions and three rotations). Spectral estimates produced measures of tremor frequency and amplitude. Mathematical models of the data, using autoregressive modelling and K-nearest neighbour classification, produced parameters used to classify, (1) the normal subjects and 24 patients (using the three rotational movements), and (2) the three patient groups (using all six movement directions). Results were given in terms of the probability of each subject belonging to the groups being classified.

Tremor frequency and amplitude showed large overlap between the groups. The screening classification produced high probabilities of correctly classifying normal subjects (>70%) and patients (>70%). The diagnostic classification produced clear differences between the patient groups (60% for essential tremor, 80% for multiple sclerosis and 60% for parkinsonism).

The ability of this assessment technique to distinguish between postural tremor in normal subjects and neurological patients suggests that it could be developed as a screening tool. Classification of tremors between the patients groups, with a high degree of sensitivity, indicates the potential for further development of the system as a diagnostic aid.     

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2-/- neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2-/- bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.     

Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder is the most common child psychiatric disorder with a prevalence rate in an Ontario study of 9% in boys and 3% in girls [Szatmari et al., 1989]. This disorder is characterized by problems in the areas of attention, overactivity, impulse control, and distractibility. Strong evidence for a genetic component has been provided from twin, family, and adoption studies [for review see Levy et al., 1998] and molecular genetic studies are in progress by several groups worldwide. The Catechol-O-Methyltransferase (COMT) gene is an interesting candidate for ADHD as it is involved in the breakdown of dopamine and norepinephrine, neurotransmitters strongly implicated in the etiology of ADHD. In addition, children with velo-cardio-facial syndrome, a deletion syndrome of the chromosomal region 22q11 where the COMT gene has been localized, often have symptoms of ADHD suggesting this gene may have an etiological role in ADHD. In this study, we have tested for linkage in ADHD families using the functional polymorphism at codon 158 that determines COMT activity [Lachman et al., 1996] and analyzed the data with the transmission disequilibrium test (TDT). A total of 77 nuclear families collected from Toronto were genotyped. We find no evidence for linkage of this polymorphism and ADHD in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:710-713, 1999.     

Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue

OBJECTIVES: This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms. METHODS: Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support. RESULTS: After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01-1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96-1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14-5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11-1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75-3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99-1.19, p < .06). CONCLUSIONS: Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.     

Replacing sedentary time with sleep,light, or moderate-to-vigorous physical activity: effects on self-regulation and executive functioning

Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life. However, it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use, which are vital for the long-term maintenance of a health behavior regimen. The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity, moderate-to-vigorous physical activity (MVPA), or sleep in a sample of older adults. This study reports baseline data collected from low-active healthy older adults (N = 247, mean age 65.4 ± 4.6 years) recruited to participate in a 6 month randomized controlled exercise trial examining the effects of various modes of exercise on brain health and function. Each participant completed assessments of physical activity self-regulatory strategy use (i.e., self-monitoring, goal-setting, social support, reinforcement, time management, and relapse prevention) and executive functioning. Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point. Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity, MVPA, or sleep. The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning. Sleep was associated with greater self-monitoring (B = .23, p = .02), goal-setting (B = .32, p < .01), and social support (B = .18, p = .01) behaviors. Substitution of sedentary time with MVPA was associated with higher accuracy on 2-item (B = .03, p = .01) and 3-item (B = .02, p = .04) spatial working memory tasks, and with faster reaction times on single (B = ?23.12, p = .03) and mixed-repeated task-switching blocks (B = ?27.06, p = .04). Substitution of sedentary time with sleep was associated with marginally faster reaction time on mixed-repeated task-switching blocks (B = ?12.20, p = .07) and faster reaction time on mixed-switch blocks (B = 17.21, p = .05), as well as reduced global reaction time switch cost (B = ?16.86, p = .01). Substitution for light intensity physical activity did not produce significant effects. By replacing sedentary time with sleep and MVPA, individuals may bolster several important domains of self-regulatory behavior and executive functioning. This has important implications for the design of long-lasting health behavior interventions. Trial Registration clinicaltrials.gov identifier NCT00438347.     

Factors associated with junior doctors’ decisions to apply for general practice training programmes in the UK: secondary analysis of data from the UKMED project

Background

The UK, like many high-income countries, is experiencing a worsening shortfall of general practitioners (GPs) alongside an increasing demand for their services. At the same time, factors influencing junior doctors’ decisions to apply for GP training are only partially understood and research in this area has been hampered by the difficulties in connecting the datasets that map the journey from student to qualified GP. The UK Medical Education Database (UKMED) has been established to ameliorate this problem by linking institutional data across the spectrum of medical education from school to specialty training. Our study aimed to use UKMED to investigate which demographic and educational factors are associated with junior doctors’ decisions to apply for GP training.

Methods

Study data, provided by the UKMED Development Group and accessed remotely, contained longitudinal educational and sociodemographic information on all doctors who entered UK medical schools in the 2007/2008 academic year and who made first-time specialty training applications in 2015. We used multivariable logistic regression models to investigate two binary outcomes, namely (1) application to GP training, possibly alongside applications to other specialties, and (2) application solely to GP training.

Results

Of 7634 doctors in the sample, 43% applied to GP training possibly alongside other specialities and 26% applied solely to GP training. The odds of applying to GP training were associated with particular demographic factors (being female, non-white or secondary educated in the UK increased the odds of application) and educational factors (non-graduate entry, intercalation and above-median academic performance during medical school all decreased the odds of application). After adjusting for these factors, both the medical school and the foundation school attended were independently associated with the odds of applying to GP training.

Conclusions

Our findings suggest that the supply and demand imbalance in UK primary care might be improved by (1) efforts to attract greater numbers of female, non-white and UK secondary-educated students into medical schools, and (2) targeting resources at medical and foundation schools that deliver doctors likely to fill significant gaps in the workforce. Further research is required to better understand inter-school differences and to develop strategies to improve recruitment of GP trainees.