Athletes and blood clots: individualized, intermittent anticoagulation management.

Essentials Athletes on anticoagulants are typically prohibited from participation in contact sports. Short-acting anticoagulants allow for reconsideration of this precedent. An individualized pharmacokinetic/pharmacodynamics study can aid patient-specific management. Many challenges and unresolved issues exist regarding such tailored intermittent dosing. SUMMARY: Athletes with venous thromboembolism (VTE) are typically prohibited from participating in contact sports during anticoagulation therapy, but such mandatory removal from competition can cause psychological and financial detriments for athletes and overlooks patient autonomy. The precedent of compulsory removal developed when options for anticoagulation therapy were more limited, but medical advances now allow for rethinking of the management of athletes with VTE. We propose a novel therapeutic approach to the treatment of athletes who participate in contact sports and require anticoagulation. A personalized pharmacokinetic/pharmacodynamics study of a direct oral anticoagulant can be performed for an athlete, which can inform the timing of medication dosing. Managed carefully, this can allow athletic participation when plasma drug concentration is minimal (minimizing bleeding risk) and prompt resumption of treatment after the risk of bleeding sufficiently normalizes (maximizing therapeutic time).

Mitrofanoff continent catheterizable conduits: top down or bottom up?

OBJECTIVE: During augmentation and Mitrofanoff procedures, conduits are usually implanted into the posterior bladder wall. Anatomical considerations may necessitate an anterior conduit. To compare the relative drainage efficiency in patients with posterior and anterior conduits, we studied their rates of bladder stone formation and urinary tract infection (UTI). MATERIALS AND METHODS: A retrospective chart review identified exstrophy patients who underwent augmentation and Mitrofanoff between 1991 and 2003. Patients with 3 years or greater follow-up were included. Fifty-four patients fit this criterion, with a conduit implanted anteriorly (33) or posteriorly (21). We compared rates of bladder stone formation and UTI. Stomal revisions and the status of the bladder neck were also noted. RESULTS: Stone formation and UTI rates were higher in the anterior conduits, although only UTI showed a statistically significant difference. Patient demographics were similar between the two groups, including age and sex. The rates of stomal complications and the bladder neck status were also similar. CONCLUSIONS: Patients with anterior conduits had an increased risk of UTI and bladder stone formation compared to those with posterior conduits, although this was not significant in the case of bladder stone rate. This may indicate sub-optimal bladder drainage and should be addressed with careful preoperative counseling and close follow-up.

A prospective study of the effectiveness of early intervention with high-risk back-injured workers--a pilot study.

INTRODUCTION: It was postulated that workers, at the sub-acute stage after injury, respond differently to clinical and occupational interventions offered in a workers' compensation environment. Individual worker risk of disability, it was further believed, would influence the effectiveness of early intervention. The objective of the current pilot study was to evaluate return to work (RTW) outcomes following proactive, combined clinical, occupational and case management-based interdisciplinary early intervention, provided in a workers' compensation environment 4-10 weeks of onset of back pain, to workers with medium and high risk for disability. METHODS: The project was a controlled study comparing conventional workers' compensation case management with integrated, interdisciplinary and multimodal early intervention (hereinafter referred to as "EI"). At baseline, risk status was determined by a validated Risk for Disability Questionnaire by Carragee et al. (Spine 5(1):24-35, 2005). Seventeen workers at high risk of protracted disability and 20 workers at moderate risk of disability received conventional case management, and 17 workers assessed at high risk of protracted disability and 18 workers at moderate risk of disability received the Early Intervention. RESULTS: At 3 months post back pain onset, no statistically significant differences were identified in RTW outcomes between conventional case management and the Early Intervention. However, by 6 months post back pain onset, workers at high risk of work disability who received the Early Intervention were significantly more likely to RTW than high risk workers who received conventional case management. In contrast, moderate risk workers continued to exhibit no statistically significant differences in RTW outcomes. CONCLUSION: Multimodal Early Intervention in the workers' compensation case management context is likely effective for workers with sub-acute back pain who are at high risk of occupational disability. The comprehensive Early Intervention is, however, likely redundant for workers who are not at high risk for disability and should not be applied indiscriminately. Further studies are required to determine longer-term Early Intervention outcomes, and to replicate the findings using a randomized control design. Also, with a larger sample size, it will be possible to determine predictors of occupational outcomes.

Viability effects and not meoitic drive cause dramatic departures from Mendelian inheritance for malic enzyme in hybrids of Tigriopus californicus populations.

The genetic basis of post-zygotic reproductive isolation is beginning to be untangled in closely related species, but less is known about the genetics of reproductive isolation between divergent populations. Here, two genes encoding malic enzyme (ME) are isolated from the copepod Tigriopus californicus and their influence upon lowered viability in F(2) hybrids of genetically divergent populations is determined. Each ME gene has diverged extensively between T. californicus populations and one gene shows evidence for a recent selective sweep. Segregation patterns of genotypes for both ME genes in adult F(2) hybrids reveal dramatic departures from Mendelian inheritance, deviations that are not seen in F(2) nauplii implying that selection is acting during development based upon the genotype at these ME genes. These results imply that selection against deleterious gene combinations and not aberrant segregation (i.e. meiotic drive) is likely to lead to dramatic departures from Mendelian inheritance observed in these crosses.

Predicting return to work after low back injury using the Psychosocial Risk for Occupational Disability Instrument: a validation study.

INTRODUCTION: This paper reports on the predictive validity of a Psychosocial Risk for Occupational Disability Scale in the workers' compensation environment using a paper and pencil version of a previously validated multimethod instrument on a new, subacute sample of workers with low back pain. METHODS: A cohort longitudinal study design with a randomly selected cohort off work for 4-6 weeks was applied. The questionnaire was completed by 111 eligible workers at 4-6 weeks following injury. Return to work status data at three months was obtained from 100 workers. Sixty-four workers had returned to work (RTW) and 36 had not (NRTW). RESULTS: Stepwise backward elimination resulted in a model with these predictors: Expectations of Recovery, SF-36 Vitality, SF-36 Mental Health, and Waddell Symptoms. The correct classification of RTW/NRTW was 79%, with sensitivity (NRTW) of 61% and specificity (RTW) of 89%. The area under the ROC curve was 84%. CONCLUSIONS: New evidence for predictive validity for the Psychosocial Risk-for-Disability Instrument was provided. IMPLICATIONS: The instrument can be useful and practical for prediction of return to work outcomes in the subacute stage after low back injury in the workers' compensation context.

A randomized comparison of a five-minute versus fifteen-minute lockout interval for PCEA during labor.

BACKGROUND: The best combination of bolus size and lockout interval for patient-controlled epidural analgesia (PCEA) is not known. This study compared a 5-min with a 15-min lockout interval. METHODS: Parturients were randomly assigned to receive PCEA with either a 5-min or a 15-min interval. All had a 15-mL loading dose, continuous background infusion 6 mL/h of 0.125% bupivacaine plus fentanyl 2 mug/mL, PCEA bolus volume 5 mL, maximum hourly dose 26 mL. Visual analogue scores for pain, nausea and pruritus, sensory levels to ice, sacral analgesia, motor power, blood pressure and fetal heart rate were assessed pre-epidural and regularly thereafter until delivery. The numbers of boluses and attempts and patient satisfaction were recorded. RESULTS: 29 patients were assigned to the 5-min group and 31 to the 15-min group, but the 15-min group contained twice as many nulliparous women. Side-effect and complication rates did not differ between groups. VAS pain scores were reduced from a median of 79 in the 15-min group and 82 in the 5-min group to a median of zero 30 min after epidural insertion. Bolus/attempt ratio was 0.88 in the 5-min vs. 0.70 in the 15-min group. The numbers of requests for physician intervention were similar. No differences in pain scores, side-effects, drug use or patient satisfaction were demonstrated. CONCLUSION: The 5-min lockout interval appears the more efficient and has been used safely in our practice for 15,000 parturients, although a larger study is required to confirm the relative efficacy, efficiency and safety of this regimen.

Preferences for sexual information resources in patients treated for early-stage prostate cancer with either radical prostatectomy or brachytherapy.

OBJECTIVE: To identify the preferences for sexual information resources of patients before and after definitive treatment for early-stage prostate cancer with either radical prostatectomy (RP) or brachytherapy. PATIENTS AND METHODS: Two hundred patients (mean age 64 years) treated with either RP or brachytherapy were recruited from radiation oncology (100) and urology (100) outpatient clinics. Patients completed a survey questionnaire to identify the types of information used, preferred sources of information, knowledge of treatments for erectile dysfunction (ED), effect of sexual function on the treatment decision, and the International Index of Erectile Function (IIEF) to assess their current level of sexual function. RESULTS: Urologists were identified as the main source of sexual information. Written information, Internet access and videos were identified as preferred sources of information before and after treatment. The effects of treatment on sexual function had no apparent significant influence on the men's definitive treatment choice. Compared with patients in the brachytherapy group, patients in the RP group reported having significantly higher levels of sexual desire (P < 0.001) after treatment, but otherwise the erectile domains of the groups were remarkably similar. Two-thirds of patients wanted more information on the effects of treatment on sexual function, and on available treatments for ED. CONCLUSIONS: These results support the need for physicians to offer patients access to information on the effect of treatment for early-stage prostate cancer on erectile function before and after treatment.

Psychosocial factors predictive of occupational low back disability: towards development of a return-to-work model.

This paper focuses on the identification and testing of potential psychosocial factors contributing to an integrated multivariate predictive model of occupational low back disability. Psychosocial predictors originate from five traditions of psychosocial research: psychopathological, cognitive, diathesis-stress, human adaptation and organizational psychology. The psychosocial variables chosen for this study reflect a full range of research findings. They were investigated using 253 subacute and chronic pain injured workers. Three outcome measures were utilized: return-to-work status, duration of disability and disability costs. The key psychosocial predictors identified were expectations of recovery and perception of health change. Also implicated, but to a lesser degree, were occupational stability, skill discretion at work, co-worker support, and the response of the workers' compensation system and employer to the disability. All psychosocial models were better at predicting who will return than who will not return to work.

Assessing pain behaviour of low-back pain patients in real time: concurrent validity and examiner sensitivity.

Several systems for measuring pain behaviour have been developed for clinical settings. The present study reports on a real-time system for coding five categories of pain behaviour for low-back pain patients: guarding, touching, sounds, words, and facial expression. Unique features of the system are the use of refined measures of facial expression and integration of the measurements with a standardized physical examination. 176 sub-acute and chronic low-back pain patients underwent a physical examination while their pain behaviour was coded. Concurrent measures of subjective pain, medically-incongruent signs, and independent global ratings of pain behaviour were taken. Analyses indicated that the pain behaviours, particularly guarding and facial expression, varied systematically with the alternative measures, supporting the concurrent validity of the behaviour observation system. While pain behaviours, especially use of words and facial expressions, were significantly associated with the examiners' independent ratings, the strength of the associations suggested that, in the absence of direct training, examiners' performance was relatively poor. Implications for training of clinicians in detecting pain behaviour are discussed.

Reliability of the lumbar flexion, lumbar extension, and passive straight leg raise test in normal populations embedded within a complete physical examination.

STUDY DESIGN: The study measured the reliability of the passive straight leg raise (SLR) test and lumbar range of motion (LROM) tests measured as continuous variables embedded within a comprehensive physical examination. OBJECTIVES: To determine the reliability of the SLR and LROM test scores when they are measured with a Cybex electronic inclinometer (Lumex, Inc., New York, NY) within a physical examination. SUMMARY OF BACKGROUND DATA: Good published empirical reliability exists for the Cybex and for SLR and LROM tests when the measurements are taken in isolation from other physical examination procedures. Reliability of the Cybex for continuous SLR and LROM measurement within a physical examination has not been assessed, however. METHODS: Forty-five participants were seen by one of two physician/physiotherapist teams. Participants were examined by both team members. The first examiner conducted the first tests and retested 1 week later (intrarater reliability). The second examined the participants the day after their first appointment (inter-rater reliability). RESULTS: Only two scores showed substantial reliability (defined as r > or = 0.60). These scores were left (r = 0.81) and right (r = 0.79) SLR intrarater reliability. All other scores fell below the specified cutoff. CONCLUSIONS: SLR and LROM scores used clinically are collected during comprehensive physical examinations. Most scores gathered under these conditions were not reliable. These findings have implications for the use of clinically derived SLR and LROM scores.

Commentary on the American Medical Association guides' lumbar impairment validity checks.

STUDY DESIGN: The American Medical Association's (AMA) Guides to the Evaluation of Permanent Impairment range of motion-based (ROM) lumbar impairment model validity checks were reviewed. Published literature of lumbar ROM (LROM) testing also was reviewed for application of the AMA validity checking protocols. OBJECTIVE: The utility and feasibility of use of the AMA Guides' ROM lumbar impairment ratings were examined. SUMMARY OF BACKGROUND DATA: Although they appear to be essential components of the ROM model, few published studies report use of these validity checks. Of at least 22 reviewed studies of LROM testing, only six studies included at least three measurements (the bare minimum) of LROM. Furthermore, only two (9.1%) reported performance of the LROM validity check. Only one, however, reported the results. METHODS: English language journals were searched on Medline using "region, lumbar," "range of motion," "validity of results," "observer variation," and "low back pain" as title and subject search terms. The study methodologies approximating the AMA Guides' specifications were included in the analysis. RESULTS: Under normal conditions of ROM measurement, 33% of three consecutive lumbar flexion and 27% of three consecutive lumbar extension measurements failed the LROM validity check. In addition, across three different experimental sessions (each with more than three consecutive LROM measurements taken) only 15 participants (33%) had valid flexion scores and only 24 participants (53%) had valid extension scores across all three sessions. CONCLUSION: Technical complications inherent in the ROM-based impairment-rating model render the validity checks difficult to perform satisfactorily and thus rarely used.

Analysis of the convergent and discriminant validity of published lumbar flexion, extension, and lateral flexion scores.

STUDY DESIGN: Articles reflecting the convergent or discriminant validity of the lumbar range of motion tests were reviewed and compared. Mean scores and standard deviations for lumber range of motion from healthy control subjects were plotted against those from patients with low back injuries. OBJECTIVE: To use published research to analyze the convergent and discriminant validity of lumbar range of motion tests for the characterization of low back pain and injury. SUMMARY OF BACKGROUND DATA: Several publications have addressed lumbar range of motion validity. Individual studies suggest that the tests possess convergent validity, but that their discriminant validity is indeterminate. METHODS: English-language journals were searched on Medline using "region," "lumbar," "range of motion," "validity of results," "observer variation," and "low back pain" as title and subject search terms. The study methods approximating the specifications of the American Medical Association Guides to the Evaluation of Permanent Impairment were included in the analysis. RESULTS: Convergent validity research showed inconsistent relations between inclinometric and radiographic lumbar range of motion measurements. Some studies showed strong relation, whereas others showed essentially no relation between the two techniques. Correlations between lumbar range of motion scores and spinal disability and function were similarly inconclusive. Studies reporting mean scores and standard deviations for lumbar range of motion measurements showed a high degree of overlap between the scores of participants with low back injuries and those without such injuries. CONCLUSIONS: Convergent and discriminant validities of the lumbar range of motion tests currently require further substantiation. Absolute lumbar range of motion scores may not be suitable as the sole determinants of low back pathology diagnosis. Implications for using the lumbar range of motion tests to characterize low back injuries in medicolegal situations are discussed.

Mental health, job satisfaction, and intention to relocate. Opinions of physicians in rural British Columbia.

OBJECTIVE: To determine the prevalence of depression and burnout among family physicians working in British Columbia's Northern and Isolation Allowance communities. Current level of satisfaction with work and intention to move were also investigated. DESIGN: Cross-sectional, mailed survey. SETTING: Family practices in rural communities eligible for British Columbia's Northern and Isolation Allowance. PARTICIPANTS: A random sample of family physicians practising in rural BC communities. Initial response rate was 66% (131/198 surveys returned); excluding physicians on leave and in temporary situations and those who received duplicate mailings gave a corrected response rate of 92% (131/142 surveys returned). MAIN OUTCOME MEASURES: Demographics; self-reported depression and burnout; Beck Depression Inventory and Maslach Burnout Inventory scores; job satisfaction; and intention to leave. RESULTS: Self-reported depression rate was 29%; the Beck Depression Inventory indicated 31% of physicians suffered from mild to severe depression. About 13% of physicians reported taking antidepressants in the past 5 years. Self-reported burnout rate was 55%; the Maslach Burnout Inventory showed that 80% of physicians suffered from moderate-to-severe emotional exhaustion, 61% suffered from moderate-to-severe depersonalization, and 44% had moderate-to-low feelings of personal accomplishment. Depression scores correlated with emotional exhaustion scores. More than half the respondents were considering relocation. CONCLUSION: Physicians working in these communities suffer from high levels of depression and very high levels of burnout and are dissatisfied with their current jobs. More than half are considering relocating. Intention to move is strongly associated with poor mental health.

Tooth-surface progression and reversal changes in fluoridated and no-longer-fluoridated communities over a 3-year period.

OBJECTIVE: To compare permanent tooth surface-specific progression/reversal changes between fluoridation-ended (F-E) and still-fluoridated (S-F) communities in British Columbia, Canada, over a 3-year period. METHODS: D1D2MFS examinations were contrasted for 2,964 schoolchildren in 1993/94 (grades 2, 3, 8 and 9) and 1996/97 (grades 5, 6, 11 and 12). Generalized Estimating Equation (GEE) models explored the relation between progression/reversal changes and fluoridation status, age, gender, socioeconomic status, and dietary/fluoride histories. RESULTS: Within a scenario of low levels of caries overall, few children had multiple surfaces progressing. At least one smooth surface progressed in 31.4% of subjects; at least one pit-and-fissure (PF) surface progressed in 43.1% of subjects. At least one smooth surface reverted in 89% of subjects who had reversible stages; at least one PF surface reverted in 23.8% of subjects who had reversible stages. GEE (smooth) indicated that odds ratios of progression were twice as large in the F-E site compared to the S-F site, and slightly increased in older participants and in participants exposed to more fluoride technologies. GEE (PF) also indicated that progression was slightly more common in the F-E site; more frequent snacking and lower parental educational attainment had modest associations with increased progression in PF surfaces. For the two types of surfaces, GEE models demonstrated that unerupted surfaces were less likely to progress than sound surfaces. No associations were found between reversals and independent variables. CONCLUSION: Progressions were found to be weakly linked to socio-demographic factors; baseline surface statuses were better predictors of progression. Using the current definitions for disease transitions, F-E communities had more frequent progressions than a S-F community.

JFC1, a novel tandem C2 domain-containing protein associated with the leukocyte NADPH oxidase.

We have employed a yeast two-hybrid system to screen a B lymphoblast-derived cDNA library, searching for regulatory components of the NADPH oxidase. Using as bait the C-terminal half of p67(phox), which contains both Src homology 3 domains, we have cloned JFC1, a novel human 62-kDa protein. JFC1 possesses two C2 domains in tandem. The C2A domain shows homology with the C2B domain of synaptotagmins. JFC1 mRNA was abundantly expressed in bone marrow and leukocytes. The expression of JFC1 in neutrophils was restricted to the plasma membrane/secretory vesicle fraction. We confirmed JFC1-p67(phox) association by affinity chromatography. JFC1-containing beads pulled down both p67(phox) and p47(phox) subunits from neutrophil cytosol, but when the recombinant proteins were used, only p67(phox) bound to JFC1, indicating that JFC1 binds to the cytosolic complex via p67(phox) without affecting the interaction between p67(phox) and p47(phox). In contrast to synaptotagmins, JFC1 was unable to bind to inositol 1,3,4,5-tetrakisphosphate but did bind to phosphatidylinositol 3,4,5-trisphosphate and to a lesser extent to phosphatidylinositol 3,4-diphosphate. From the data presented here, it is proposed that JFC1 is acting as an adaptor protein between phosphatidylinositol 3-kinase products and the oxidase cytosolic complex.

Role of laparoscopic salpingostomy in the treatment of hydrosalpinx.

OBJECTIVE: To determine pregnancy rates after laparoscopic salpingostomy in occlusive distal tubal disease. To evaluate the relative impact of various historical, physical, and operative factors on pregnancy outcome using a multivariate statistical analysis. DESIGN: Prospective cohort. SETTING: University-affiliated tertiary care infertility clinic. PATIENT(S): One hundred thirty-nine infertile women with occlusive distal tube disease. INTERVENTION(S): Laparoscopic salpingostomy. MAIN OUTCOME MEASURE(S): The occurrence of intrauterine (IUP) and ectopic pregnancy (EP). RESULT(S): The overall IUP and EP rates were 24.5% and 16.5%, respectively. Analysis of historical variables, assessed independently, demonstrated a significantly higher IUP rate with a positive history of gonorrhea and a significantly higher EP rate with a positive history of pelvic inflammatory disease, lack of history of intrauterine device (IUD) usage, or the performance of a bilateral procedure. The logistic regression model to predict intrauterine pregnancy had an overall predictive value of 77.5% and included the following significant variables: secondary infertility, positive history of gonorrhea, and the operative finding of moderate periadnexal adhesions. The logistic regression model to predict ectopic pregnancy had an overall predictive value of 89.0% and included the following significant variables: previous ectopic pregnancy, negative history of IUD use, positive history of PID, a bilateral procedure, and perihepatic adhesions. CONCLUSION(S): Operative laparoscopy may be effective for the correction of hydrosalpinges in selected patients. The probability of achieving an intrauterine or an ectopic pregnancy can be predicted based on combinations of significant variables.

Patterns of dental caries following the cessation of water fluoridation.

OBJECTIVES: To compare prevalence and incidence of caries between fluoridation-ended and still-fluoridated communities in British Columbia, Canada, from a baseline survey and after three years. METHODS: At the baseline (1993/4 academic year) and follow-up (1996/7) surveys, children were examined at their schools. Data were collected on snacking, oral hygiene, exposure to fluoride technologies, and socio-economic level. These variables were used together with D1D2MFS indices in multiple regression models. RESULTS: The prevalence of caries (assessed in 5,927 children, grades 2, 3, 8, 9) decreased over time in the fluoridation-ended community while remaining unchanged in the fluoridated community. While numbers of filled surfaces did not vary between surveys, sealed surfaces increased at both study sites. Caries incidence (assessed in 2,994 life-long residents, grades 5, 6, 11, 12) expressed in terms of D1D2MFS was not different between the still-fluoridating and fluoridation-ended communities. There were, however, differences in caries experienced when D1D2MFS components and surfaces at risk were investigated in detail. Regression models did not identify specific variables markedly affecting changes in the incidence of dental decay. CONCLUSIONS: Our results suggest a complicated pattern of disease following cessation of fluoridation. Multiple sources of fluoride besides water fluoridation have made it more difficult to detect changes in the epidemiological profile of a population with generally low caries experience, and living in an affluent setting with widely accessible dental services. There are, however, subtle differences in caries and caries treatment experience between children living in fluoridated and fluoridation-ended areas.

A randomized controlled trial to evaluate the effectiveness of an exercise program in women with rheumatoid arthritis taking low dose prednisone.

OBJECTIVE: To evaluate the effects of a 12 month, weight bearing, aerobic exercise program on disease activity, physical function, and bone mineral density (BMD) in women with rheumatoid arthritis (RA) taking low dose prednisone. METHODS: A group of women with RA (n = 23) not receiving steroid therapy and in American College of Rheumatology functional class I or II was compared to 30 steroid treated patients with similar demographics. The latter group was randomized to usual care (n = 16) or an aerobic, weight bearing exercise program (n = 14) 3 times a week for 12 months. All subjects were recruited from an outpatient rheumatology clinic or physical therapy department and met the study inclusion criteria. Outcome measures included disease activity (erythrocyte sedimentation rate, active joint count), physical function (Health Assessment Questionnaire disability index, activity level) and BMD of the spine and femoral neck (by dual energy projection radiology). RESULTS: Subjects in the exercise group had a small but nonsignificant decrease in disease activity and statistically significant improvements in function (p = 0.05) and activity levels (p = 0.05). BMD remained unchanged in the exercise group, decreased significantly (p = 0.004) in the nonsteroid comparison group (hip), and changed nonsignificantly in the control group. However, between-group changes in spinal BMD of the steroid treated groups was not significant (p = 0.09). CONCLUSION: Women with RA taking low dose steroid therapy can safely participate in a dynamic, weight bearing exercise program with positive effects on their physical function, activity and fitness levels, and BMD with no exacerbation of disease activity.