Rory Wolfe

Decompressive Craniectomy in Diffuse Traumatic Brain Injury

BACKGROUND It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure. METHODS From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months. RESULTS Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%). CONCLUSIONS In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

The reliability of three-dimensional kinematic gait measurements: A systematic review

BACKGROUND/AIM Three-dimensional kinematic measures of gait are routinely used in clinical gait analysis and provide a key outcome measure for gait research and clinical practice. This systematic review identifies and evaluates current evidence for the inter-session and inter-assessor reliability of three-dimensional kinematic gait analysis (3DGA) data. METHOD A targeted search strategy identified reports that fulfilled the search criteria. The quality of full-text reports were tabulated and evaluated for quality using a customised critical appraisal tool. RESULTS Fifteen full manuscripts and eight abstracts were included. Studies addressed both within-assessor and between-assessor reliability, with most examining healthy adults. Four full-text reports evaluated reliability in people with gait pathologies. The highest reliability indices occurred in the hip and knee in the sagittal plane, with lowest errors in pelvic rotation and obliquity and hip abduction. Lowest reliability and highest error frequently occurred in the hip and knee transverse plane. Methodological quality varied, with key limitations in sample descriptions and strategies for statistical analysis. Reported reliability indices and error magnitudes varied across gait variables and studies. Most studies providing estimates of data error reported values (S.D. or S.E.) of less than 5 degrees , with the exception of hip and knee rotation. CONCLUSION This review provides evidence that clinically acceptable errors are possible in gait analysis. Variability between studies, however, suggests that they are not always achieved.

Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women.

ObjectiveCirculating testosterone in women declines during the late reproductive years such that otherwise healthy women in their 40s have approximately half the testosterone level as women in their 20s. Despite this, research showing the benefits of androgen replacement has been limited to the postmenopausal years. In view of the known premenopausal physiological decline in testosterone, we have evaluated the efficacy of transdermal testosterone therapy on mood, well-being, and sexual function in eugonadal, premenopausal women presenting with low libido. DesignPremenopausal women with low libido participated in a randomized, placebo-controlled, crossover, efficacy study of testosterone cream (10 mg/day) with two double-blind, 12-week, treatment periods separated by a single-blind, 4-week, washout period. ResultsThirty-four women completed the study per protocol, with 31 women (mean age 39.7 ± 4.2 years; serum testosterone 1.07 + 0.50 nmol/L) providing complete data. Testosterone therapy resulted in statistically significant improvements in the composite scores of the Psychological General Well-Being Index [+12.9 (95% CI, +4.6 to +21.2), P = 0.003] and the Sabbatsberg Sexual Self-Rating Scale [+15.7 (95% CI, +6.5 to +25.0), P = 0.001] compared with placebo. A mean decrease in the Beck Depression Inventory score approached significance [−2.8 (95% CI, −5.7 to +0.1), P = 0.06]. Mean total testosterone levels during treatment were at the high end of the normal range, and estradiol was unchanged. No adverse effects were reported. ConclusionsTestosterone therapy improves well-being, mood, and sexual function in premenopausal women with low libido and low testosterone. As a substantial number of women experience diminished sexual interest and well-being during their late reproductive years, further research is warranted to evaluate the benefits and safety of longer-term intervention.

Hip displacement in cerebral palsy

BACKGROUND Hip displacement is considered to be common in children with cerebral palsy but the reported incidence and the proposed risk factors vary widely. Knowledge regarding its overall incidence and associated risk factors can facilitate treatment of these children. METHODS An inception cohort was generated from the Victorian Cerebral Palsy Register for the birth years 1990 through 1992, inclusive, and multiple data sources pertaining to the cohort were reviewed during 2004. Gross motor function was assessed for each child and was graded according to the Gross Motor Function Classification System (GMFCS), which is a valid, reliable, five-level ordinal grading system. Hip displacement, defined as a migration percentage of >30%, was measured on an anteroposterior radiograph of the pelvis with use of a reliable technique. RESULTS A full data set was obtained for 323 (86%) of 374 children in the Register for the birth years 1990 through 1992. The mean duration of follow-up was eleven years and eight months. The incidence of hip displacement for the entire birth cohort was 35%, and it showed a linear relationship with the level of gross motor function. The incidence of hip displacement was 0% for children with GMFCS level I and 90% for those with GMFCS level V. Compared with children with GMFCS level II, those with levels III, IV, and V had significantly higher relative risks of hip displacement (2.7, 4.6, and 5.9, respectively). CONCLUSIONS Hip displacement is common in children with cerebral palsy, with an overall incidence of 35% found in this study. The risk of hip displacement is directly related to gross motor function as graded with the Gross Motor Function Classification System. This information may be important when assessing the risk of hip displacement for an individual child who has cerebral palsy, for counseling parents, and in the design of screening programs and resource allocation.

The number of years lived with obesity and the risk of all-cause and cause-specific mortality

BACKGROUND The role of the duration of obesity as an independent risk factor for mortality has not been investigated. The aim of this study was to analyse the association between the duration of obesity and the risk of mortality. METHODS A total of 5036 participants (aged 28-62 years) of the Framingham Cohort Study were followed up every 2 years from 1948 for up to 48 years. The association between obesity duration and all-cause and cause-specific mortality was analysed using time-dependent Cox models adjusted for body mass index. The role of biological intermediates and chronic diseases was also explored. RESULTS The adjusted hazard ratio (HR) for mortality increased as the number of years lived with obesity increased. For those who were obese for 1-4.9, 5-14.9, 15-24.9 and ≥ 25 years of the study follow-up period, adjusted HRs for all-cause mortality were 1.51 [95% confidence interval (CI) 1.27-1.79], 1.94 (95% CI 1.71-2.20), 2.25 (95% CI 1.89-2.67) and 2.52 (95% CI 2.08-3.06), respectively, compared with those who were never obese. A dose-response relation between years of duration of obesity was also clear for all-cause, cardiovascular, cancer and other-cause mortality. For every additional 2 years of obesity, the HRs for all-cause, cardiovascular disease, cancer and other-cause mortality were 1.06 (95% CI 1.05-1.07), 1.07 (95% CI 1.05-1.08), 1.03 (95% CI 1.01-1.05) and 1.07 (95% CI 1.05-1.11), respectively. CONCLUSIONS The number of years lived with obesity is directly associated with the risk of mortality. This needs to be taken into account when estimating its burden on mortality.

Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma

The effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAFV600E mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAFV600E were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy‐five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAFV600E 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm2 (BRAFV600E 40%, WT 55%). When compared to WT, multivariate analysis of melanoma‐specific survival (MSS) identified NRAS mutations as an adverse prognostic factor [hazard ratio (HR) 2.96; P = 0.04] but not BRAFV600E mutations (HR 1.73; P = 0.23). NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAFV600E and WT melanoma and independently of this, with shorter MSS.

Substantial Intentional Weight Loss and Mortality in the Severely Obese

Objective:To compare all-cause mortality in a surgical weight loss cohort with a similarly aged, obese population-based cohort. Summary Background Data:Significant weight loss following bariatric surgery improves the comorbidities associated with obesity. Improved survival as a result of surgical weight loss has yet to be clearly demonstrated using clinical data. Methods:The surgical weight loss cohort was a series of consecutive patients treated with a laparoscopic adjustable gastric band in Melbourne between June 1994 and April 2005. The Melbourne Collaborative Cohort Study (MCCS) provided a community control cohort, recruited between 1992 and 1994 and followed to June 2005 to determine vital status. Height and weight were recorded at baseline in both studies. Subjects between 37 and 70 years and with a body mass index (BMI) of ≥35 were included. Vital status was determined by follow-up and searching of death registries. Survival time was compared using Kaplan-Meier estimates, and hazard of death was determined using Cox regression, adjusting for sex, age at baseline, and BMI at baseline. Results:Of 966 weight loss patients (mean age 47 years, mean BMI 45 kg/m2), the median follow-up time was 4 years. Mean weight loss after 2 years was 22.8% ± 9% (58% of excess weight). The MCCS cohort included 2119 severely obese members (mean age, 55 years; mean BMI, 38 kg/m2; median follow-up time, 12 years). There were 4 deaths in the weight loss cohort and 225 deaths in the MCCS cohort. Weight loss patients had 72% lower hazard of death than the community control cohort (hazard ratio, 0.28; 95% confidence interval, 0.10–0.85). Conclusions:Substantial surgical weight loss in a morbidly obese population was associated with a significant survival advantage.

Improved functional outcomes for major trauma patients in a regionalized, inclusive trauma system.

Objective:To describe outcomes of major trauma survivors managed in an organized trauma system, including the association between levels of care and outcomes over time. Background:Trauma care systems aim to reduce deaths and disability. Studies have found that regionalization of trauma care reduces mortality but the impact on quality of survival is unknown. Evaluation of a trauma system should include mortality and morbidity. Methods:Predictors of 12-month functional (Glasgow Outcome Scale—Extended) outcomes after blunt major trauma (Injury Severity Score >15) in an organized trauma system were explored using ordered logistic regression for the period October 2006 to June 2009. Data from the population-based Victorian State Trauma Registry were used. Results:There were 4986 patients older than 18 years. In-hospital mortality decreased from 11.9% in 2006–2007 to 9.9% in 2008–2009. The follow-up rate at 12 months was 86% (n = 3824). Eighty percent reported functional limitations. Odds of better functional outcome increased in the 2007–2008 [adjusted odds ratio (AOR): 1.22; 95% CI: 1.05, 1.41] and 2008–2009 (AOR: 1.16; 95% CI: 1.01, 1.34) years compared with 2006–2007. Cases managed at major trauma services (MTS) achieved better functional outcome (AOR: 1.22; 95% CI: 1.03, 1.45). Female gender, older age, and lower levels of education demonstrated lower adjusted odds of better outcome. Conclusions:Despite an annual decline in mortality, risk-adjusted functional outcomes improved over time, and cases managed at MTS (level-1 trauma centers) demonstrated better functional outcomes. The findings provide early evidence that this inclusive, regionalized trauma system is achieving its aims.

Cerebral palsy in Victoria : Motor types, topography and gross motor function

Objectives:  To study the relationships between motor type, topographical distribution and gross motor function in a large, population‐based cohort of children with cerebral palsy (CP), from the State of Victoria, and compare this cohort to similar cohorts from other countries.

Psychometric properties of the quality of life questionnaire for children with CP

This paper describes the development and psychometric properties of a condition‐specific quality of life instrument for children with cerebral palsy (CP QOL‐Child). A sample of 205 primary caregivers of children with CP aged 4 to 12 years (mean 8y 5mo) and 53 children aged 9 to 12 years completed the CP QOL‐Child. The children (112 males, 93 females) were sampled across Gross Motor Function Classification System (GMFCS) levels (Level I=18%, II=28%, III=14%, IV=11%, V=27%). Primary caregivers also completed other measures of child health (Child Health Questionnaire; CHQ), QOL (KIDSCREEN), and functioning (GMFCS). Internal consistency ranged from 0.74 to 0.92 for primary caregivers and from 0.80 to 0.90 for child self‐report. For primary caregivers, 2‐week test‐retest reliability ranged from 0.76 to 0.89. The validity of the CP QOL is supported by the pattern of correlations between CP QOL‐Child scales with the CHQ, KIDSCREEN, and GMFCS. Preliminary statistics suggest that the child self‐report questionnaire has acceptable psychometric properties. The questionnaire can be freely accessed at http://www.deakin.edu.ac/hmnbs/chase/cerebralpalsy/cp_qol_home.php