Analysis of Calcaneal Bone Mineral Density (cBMD) in Healthy College Students.

BACKGROUND: There is limited evidence describing the relationship between calcaneal bone mineral density (cBMD) and activity level, menstrual history, or the development of bone stress injury (BSI). HYPOTHESIS/PURPOSE: The purposes of this study were to: 1) examine the influence of physical activity on cBMD in healthy college students (HCS), 2) determine if there is an association between cBMD, body mass index (BMI), sex, menstrual history, and history of BSI in HCS, and 3) compare the cBMD of HCS to cBMD data collected on intercollegiate athletes (ICA) from a previous study. STUDY DESIGN: Cross-sectional design. METHODS: This cross-sectional study recruited a convenience sample of HCS at one institution. Subjects provided self-reported injury and menstrual history, completed a physical activity questionnaire, and cBMD and BMI measures were obtained. Descriptive statistics, statistical analyses of relationships (Chi-square and relative risk), logistic regression, and differences (t-tests) were used in the statistical analyses. RESULTS: One hundred three HCS (82 female, 21 male; age 21.9 ± 1.13) consented to participate. The composite score for work, leisure, and sport activity ranged from 5.6 to 11.1 (7.9 ± 1.1) for HCS subjects. There was no significant correlation between cBMD and physical activity in HCS, however, a significant correlation was found between reported age of onset of menstruation and left and right cBMD (r = -0.22 and r = -0.23; p < 0.05) and history of secondary amenorrhea and history of BSI (r = 0.32; p < 0.05). There was no difference in cBMD between the male ICA and male HCS, but highly significant differences in cBMD between the female ICA and female HCS groups (p < 0.000). CONCLUSIONS: Age of menarche and secondary amenorrhea are significantly associated with cBMD and history of BSI in HCS subjects, respectively. Differences in cBMD among the HCS subjects were not related to activity level. cBMD was significantly lower in female HCS as compared to female ICA. This difference in cBMD between ICA and HCS may be activity related. LEVEL OF EVIDENCE: Level 3.

Compound asset sharing initiatives between pharmaceutical companies, funding bodies, and academia: Learnings and successes.

Over recent years, there have been several initiatives to gain access to compounds which have been deprioritized by pharmaceutical companies, but which have a data package allowing them to be used in human experimental medicine studies. Such compounds provide an invaluable resource for probing human biology and disease pathology, for improving translational capabilities, and ultimately for repurposing to new therapeutic indications. The authors have been involved with the setting up of the Medicine's Chest initiative, which aimed to access compounds for the use in clinical studies of the central nervous system. Other initiatives include those set up by AstraZeneca, the Medical Research Council in the UK and the National Center for Advancing Translational Sciences in the US. The purpose of this editorial is to provide an update on progress with some of these initiatives, and to identify some learnings for future endeavours.

Demographic and clinical predictors of response to internet-enabled cognitive-behavioural therapy for depression and anxiety.

BACKGROUND: Common mental health problems affect a quarter of the population. Online cognitive-behavioural therapy (CBT) is increasingly used, but the factors modulating response to this treatment modality remain unclear. AIMS: This study aims to explore the demographic and clinical predictors of response to one-to-one CBT delivered via the internet. METHOD: Real-world clinical outcomes data were collected from 2211 NHS England patients completing a course of CBT delivered by a trained clinician via the internet. Logistic regression analyses were performed using patient and service variables to identify significant predictors of response to treatment. RESULTS: Multiple patient variables were significantly associated with positive response to treatment including older age, absence of long-term physical comorbidities and lower symptom severity at start of treatment. Service variables associated with positive response to treatment included shorter waiting times for initial assessment and longer treatment durations in terms of the number of sessions. CONCLUSIONS: Knowledge of which patient and service variables are associated with good clinical outcomes can be used to develop personalised treatment programmes, as part of a quality improvement cycle aiming to drive up standards in mental healthcare. This study exemplifies translational research put into practice and deployed at scale in the National Health Service, demonstrating the value of technology-enabled treatment delivery not only in facilitating access to care, but in enabling accelerated data capture for clinical research purposes. DECLARATION OF INTEREST: A.C., S.B., V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety disorders; cognitive behavioural therapies; depressive disorders; individual psychotherapy.

Inter/Intraobserver Reliability of T1 Pelvic Angle (TPA), a Novel Radiographic Measure for Global Sagittal Deformity.

STUDY DESIGN: Reliability analysis. OBJECTIVE: To assess intra- and interobserver agreement of the T1 pelvic angle (T1PA), a novel radiographic measure of spinal sagittal alignment. Orthopedic surgeons of various levels of experience measured the T1PA in a series of healthy adult volunteers. The relationship of the TIPA to pelvic position was also assessed. SUMMARY OF BACKGROUND DATA: Recent literature suggests that the T1PA is a more reliable measure of global sagittal alignment than traditional measurements (i.e., sagittal vertical axis). Previous research focuses on postoperative patients with known spinal deformity. No published research exists evaluating the use of T1PA on healthy subjects without spinal deformity. The purpose of this study is: (1) to assess the reliability of measurements of the T1PA, (2) to examine its relationship to pelvic position. METHODS: Seven evaluators of varying orthopedic experience measured the T1PA in 50 healthy adult volunteers. Subjects were radiographed in each of three pelvic positions: resting, maximal anterior pelvic rotation, and maximal posterior pelvic rotation. After a washout period, the measurement was repeated. Using intraclass correlation coefficients, the intra- and inter-rater agreement for the T1PA was measured. The collected data was also used to determine the accuracy of this measurement and its relationship to pelvic position. RESULTS: A very high level of agreement was found in measurements of the T1PA (intraclass correlation coefficients r = 0.98). At each pelvic position, all examiners had excellent intrarater reliability, > 0.85. The inter-rater reliability, compared with a gold standard, consistently measured the T1PA within ±â€Š2°. The data also shows that the T1PA changes with pelvic rotation. CONCLUSION: T1PA is a reproducible and reliable measure of global sagittal alignment regardless of the level of training. The T1PA varies based on pelvic rotation; this variation must be taken into account when assigning an absolute target for correction. LEVEL OF EVIDENCE: 4.

The effect of pelvic motion on spinopelvic parameters.

BACKGROUND CONTEXT: To date, many studies have examined how pelvic position affects the spinal curvature and spinopelvic parameters. However, these studies focus on a static relationship, comparing pelvis and spine in a relaxed or baseline position only. Indeed, the spinopelvic connection is dynamic, as subjects can easily be taught to rotate their pelvis anteriorly or posteriorly on the femoral head, all while maintaining an erect posture. Therefore, for a true understanding of pelvic influence on the spinal column, it is necessary to examine spinopelvic parameters in multiple pelvic positions within the same subject. PURPOSE: The objective of this study was to examine the dynamic effect of pelvic motion on the spine and associated radiographic parameters. STUDY DESIGN: This is a single-center, cross-sectional study of 50 healthy, asymptomatic volunteers. PATIENT SAMPLE: Subjects were recruited and screened based on the following criteria: between 18 and 79 years of age; no known spinal, pelvic, or lower extremity pain lasting for >48 hours; no history of spinal, pelvic, or lower extremity dysfunction requiring medical care; no radiographic evidence of spinal or pelvic abnormality, scoliosis deformity, or other associated spinal pathologies; not currently pregnant and with no possibility of being pregnant; and a body mass index of <30. 64. The subjects were screened and 14 were excluded for a total of 50 subjects. OUTCOME MEASURES: The outcome measures included thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic tilt (PT), sacral slope (SS), and pelvic incidence (PI). MATERIALS AND METHODS: This study was funded by a Small Exploratory Research Grant from the Scoliosis Research Society. Each subject was instructed and observed to stand in three different positions: pelvic resting, anterior pelvic rotation, and posterior pelvic rotation. Lateral standing radiographs were taken in each position and each image was examined by an orthopedic spine surgeon who digitally measured the TK, LL, SVA, PT, SS, and PI. The data were then statistically examined to determine the affect of pelvic position on each parameter. RESULTS: Subjects demonstrated a measurable, statistically significant change in each parameter with pelvic rotation. There was a clear pattern of change for LL, PT, and SS with the anterior and posterior pelvic rotations. A change in LL demonstrated a strong correlation with changes in all measured parameters with pelvic rotation. CONCLUSIONS: In asymptomatic subjects, pelvic motion affects the position of the spinal column and resultant spinopelvic parameters. The results of this study demonstrate that one can intentionally change the position of the pelvis and the adjacent spinal column in space. Knowledge of this relationship is important to the understanding of sagittal balance and could influence the treatment of patients with spinal deformity.

Pelvic incidence: a fixed value or can you change it?

BACKGROUND CONTEXT: There has been renewed interest in the pelvic vertebrae by spinal surgeons recently. Those involved in working with patients with adult spinal deformity focus on the position of the fused spine as it relates to the pelvis, and determine success or failure by specific numbers for given pelvic parameters. The pelvic parameters that are commonly measured for these patients are pelvic tilt, sacral slope, and pelvic incidence (PI). Out of the three, PI has always been considered to be the fixed measurement, whereas pelvic tilt and sacral slope have the capacity to change in relation to external forces. The assumption that the PI does not change has not been proven in a healthy, asymptomatic population. PURPOSE: This study aimed to investigate the differences in PI between three pelvic positions used in common functional activities: resting baseline pelvic posture, maximal anterior pelvic rotation, and maximal posterior pelvic rotation. STUDY DESIGN/SETTING: This was a randomized, prospective study of 50 healthy, asymptomatic, individuals who were recruited from the vicinity of our institution. PATIENT SAMPLE: Fifty patients (16 men with a mean age of 26.5±12.1 years; 34 women with a mean age of 27.2±10.8 years) were recruited for this study. Initial screening occurred by telephone. The inclusion criteria consisted of participants being between 18 and 79 years of age, no previous history of spine, pelvic, or lower extremity pain which had lasted longer than 48 hours, or history of any disorder in the spine, pelvis, or lower extremity that had required medical care. Female patients could not be pregnant at the time of participation. OUTCOME MEASURES: Changes in PI were assessed by examining the differences between the values of the PI with each change in pelvic position: resting to maximal anterior pelvic rotation and resting to maximal posterior pelvic rotation. Inter-rater reliability was assessed using Cronbach's alpha. METHODS: This study was funded by a Small Exploratory Grant from the Scoliosis Research Society. All subjects had an initial posterior-anterior and lateral radiograph taken in their resting pelvic position. If no spinal deformity was noted, each subject was instructed to maximally rotate their pelvis anteriorly and an immediate lateral radiograph was taken. The subject was then instructed to maximally rotate their pelvis posteriorly and an immediate lateral radiograph was again taken. Radiographic measurements of PI were independently measured by a board-certified, fellowship trained orthopedic spine surgeon and a board-certified musculoskeletal radiologist after defining and agreeing to the specific manner of measurement. RESULTS: Pelvic incidence values changed in 44 of 50 subjects (88%) when they maximally anteriorly rotated their pelvis from the resting pelvic position. The mean change was 2.9°, with 23 of 50 subjects (46%) changing ≥3°. Pelvic incidence values changed in 40 of 50 subjects (80%) when they maximally posteriorly rotated their pelvis from the resting position. The mean change was 2.82° with 27 of 50 subjects (54%) changing by ≥3°. CONCLUSIONS: This study demonstrated that for a high percentage of the healthy subjects who participated, the PI changed when the subjects varied their pelvic position. This questions the assumption that PI is a fixed parameter and suggests a potential functional motion at the sacroiliac joint. It also supports the idea that intentionally changing one's posture could lead to a change in PI, an idea that could have ramifications in surgical cases.

Key role of publication of clinical data for target validation.

Drug discovery productivity has failed to improve markedly in recent years and a key issue is high attrition due to efficacy failures in initial proof-of concept clinical studies. This reflects the fact that preclinical "target validation" studies do not always translate into man, where ultimate target validation must reside. Given these facts, it is easy to see the importance of results from those first clinical validation studies for overall target validation. There are various initiatives to promote the publication of clinical data, but many clinical results, particularly negative results, remain unpublished, are published in obscure places or are published after a considerable delay. This gives rise to the potential that vast sums of money could be spent on compounds for which the molecular target has essentially been invalidated, but the data are not publicly available. Pharmacology, Research and Perspectives has indicated that it will welcome publication of all data pertinent to target validation, particularly negative data (clinical and preclinical), and it will do so in a form that should be relatively rapid and easy to achieve.

Insufflation using carbon dioxide versus room air during colonoscopy: comparison of patient comfort, recovery time, and nursing resources.

The standard of practice for colonoscopy is room air insufflation. Recent research demonstrates safety and significant decrease in postcolonoscopy discomfort from distention when carbon dioxide (CO2) is used during insufflation. Reducing abdominal pain after colonoscopy may lead to increased acceptance of colonoscopy screening for colorectal cancer. This study aims to compare patient comfort intra- and postprocedure, length of recovery, and nursing time in patients undergoing colonoscopy using room air vs. CO2 insufflation. This study uses an experimental design with patients randomly assigned to either room air or CO2 during colonoscopy. Physician endoscopists, postprocedure nurses, and patients were blinded to assignment. Prior bowel surgery, inflammatory bowel disease, or inability to consent excluded participants. Outcome measures included discomfort assessment, nursing tasks, and recovery time.Of 191 participants, 177 were men and 14 were women; 94 received room air; 97 received CO2. Patients insufflated with room air reported higher levels of some measures of discomfort: (a) during colonoscopy (p = .02), (b) on admission to recovery (p = .001), and (c) on discharge from recovery (p = .001). Patients receiving room air required more nursing tasks in recovery (p = .001) and more total nursing time (p = .001).Compared with room air, CO2 insufflation increases patient comfort and decreases nursing tasks and time.

Lower extremity overuse bone injury risk factors in collegiate athletes: a pilot study.

BACKGROUND AND PURPOSE: There is limited evidence regarding risk factors for lower extremity overuse bone injury (LEOBI) in collegiate athletes. The purposes of the study were to: 1) determine incidence of LEOBI in selected sports and its impact on athletic participation and ADL, 2) assess risk relationships between LEOBI and selected risk factors, and 3) establish the viability of using calcaneal densitometry as a screening tool to identify risk for LEOBI. STUDY DESIGN: Prospective analytical cohort design. METHODS: Collegiate athletes in selected sports (swimming/diving, women's soccer, field hockey, cross-country/track) at one university were invited to participate. Consenting athletes completed an initial questionnaire including demographic information, history, and menstrual function. Measurements included height/weight, hip abductor strength, foot posture index, and calcaneal bone mineral density. Athletes were monitored for potential LEOBI for nine months and an algorithm was used to determine if physician referral was required. The primary outcome of interest was the occurrence of physician-diagnosed LEOBI. If LEOBI was diagnosed by the physician, the athlete completed a follow-up visit including a repeat bone mineral density scan. All athletes were invited for a repeat scan at the end of the year and completed a final questionnaire. Athlete demographics were summarized using descriptive statistics and differences in continuous risk factors were analyzed using t-tests and ANOVA. Finally, risk relationships for categorical variables were analyzed using chi-square and relative risk. RESULTS: 84 athletes (64 female, 20 male) consented to participate. Over the study period, eight athletes (one male, seven females) were diagnosed with LEOBI (LEOBI group), five with stress fractures and three with medial tibial stress syndrome. The other 76 athletes who did not have a diagnosis of LEOBI were placed in the non-LEOBI group. Five of the eight were cross-country/track athletes; no swimming/diving athletes had bone injury. Sport (cross-country/track) had a significant relative risk value of 2.26 (95% CI = 1.18-4.32) for LEOBI. There was no association between LEOBI occurrence and sex, hip abductor strength, body mass index, foot type, and menstrual function. There was no difference in bone mineral density at initial or follow-up measures between LEOBI and non-LEOBI groups (p>.05) when analyzing all athletes. When analyzing ground-based athletes only at follow-up (n=44), athletes with LEOBI had lower bone mineral density of right (p = .05) and left (p =.07) calcaneus. The relative risk for developing LEOBI based on calcaneal bone mineral density below the mean of the study participants was 2.1 (95%CI = 1.09-3.35) on the left and 1.53 (95% CI=.80- 3.06) on the right. CONCLUSION: The incidence of LEOBI in this population of athletes was approximately 10%. Risk factors were sport (cross-country/track) and decreased left calcaneal bone mineral density. This study supports the use of calcaneal bone mineral density as a screening measurement for LEOBI risk and suggests the need for further investigation into additional LEOBI risk factors. LEVEL OF EVIDENCE: 2.

Multiple mechanisms have been tested in pain--how can we improve the chances of success?

Recent advances in understanding the pathophysiology of pain have led to a wealth of molecular targets for novel analgesic drugs and many clinical drug trials. There have been successes, like the gabapentinoids for neuropathic pain and calcium channel blockers for otherwise intractable pain states; and drugs which show promise in clinical trials, like nerve growth factor inhibitors and p38 kinase inhibitors. Unfortunately there have also been a number of failures. We suggest factors which might predispose to success, for example some clinical precedence for the mechanism in pain or a genetic link for the mechanism, for example a mutation linked to a pain syndrome. We also stress the importance of demonstrating molecular target engagement with a novel compound and suggest pain biomarkers which can be used for mechanistic drug profiling.

A survey of exercise-related leg pain in community runners.

PURPOSE/BACKGROUND: Exercise-related leg pain (ERLP) is a common problem in runners. The purposes of this study were to 1) report ERLP occurrence among adult community runners; 2) determine ERLP impact on daily activities; and 3) determine if there is a relationship between ERLP occurrence and selected potential risk factors including sex, age, years of running, ERLP history, body mass index (BMI), orthotic use, menstrual function, and training variables. METHODS: Community runners registered for a local race were invited to complete a questionnaire including demographics and potential risk factors. Analyses of differences (t-test) and relationships (Chi-square) were conducted and relative risk (RR) values were calculated. RESULTS: 225 registered runners (105 male, 120 female) participated; 63.6% reported ERLP history, and 35.1% reported ERLP in the 3 months preceding the race with bilateral medial ERLP as the most common presentation. Of the 79 runners who experienced ERLP during the 3 months preceding the race, ERLP caused 41.8% to reduce their running and interfered with walking or stair climbing in < 10%. Chi square analyses showed no significant association of sex, menstrual function, orthotic use, or BMI with ERLP occurrence. Significant associations were observed between ERLP history and ERLP occurrence in the previous year (RR=3.39; 2.54-4.52 95% CI), and between ERLP in the 3 months preceding the race and both years running and training mileage. Greater ERLP occurrence was observed in runners with less than 3 years experience (RR = 1.53; 1.08-2.17 95% CI) and runners who ran fewer than 15 miles/week (RR = 1.47; 1.04-2.08 95% CI). Those runners with < 3 years running experience and a race pace of 9 min/mile or > were at greater risk for ERLP when compared to other participants (RR=1.53; 1.07-2.18 95% CI). CONCLUSION: Interfering ERLP was common among this group of community runners. Risk factors included ERLP history, training mileage < 15 miles/week, and < 3 years running experience. Further investigation is warranted to identify factors which may increase a community runner's risk of developing ERLP. LEVEL OF EVIDENCE: 2b.

The effect of foot orthotic use on exercise related leg pain in cross country athletes.

OBJECTIVES: The purposes of this research were to (1) investigate the effect of foot orthotic use on exercise related leg pain (ERLP) in cross-country (XC) athletes, and (2) determine if an association between foot type and foot orthotic use exists. DESIGN: Prospective cohort design. SETTING: High schools and colleges in a Midwestern metropolitan region. PARTICIPANTS: 213 high school and college XC athletes (107 male, 106 female). MATERIALS/METHODS: Participants were seen before the fall XC season for classification of foot type, visual orthotic inspection, and questionnaire completion regarding foot orthotic use and ERLP. Statistical analysis of relationships (chi-square) was conducted. RESULTS: 37 of the 213 XC athletes (17.4%) used foot orthotics; 31 of the 37 athletes using foot orthotics (83.8%) reported a history of ERLP. Of these 31 athletes, 17 (54.8%) were using orthotics for ERLP and 15 reported a decrease in ERLP with orthotic use. Fourteen athletes were using orthotics for a reason other than ERLP and only 2 reported a decrease in ERLP with orthotic use. Athletes using orthotics included all three foot types (pronated, neutral, supinated) with no relationship between orthotic use and foot type. CONCLUSION: One-sixth of the XC athletes used foot orthotics and most using orthotics for ERLP reported a decrease in ERLP symptoms. The majority of athletes using orthotics for reasons other than ERLP reported no change in ERLP symptoms. There was no association between foot type and orthotic use.

Diabetic colon preparation comparison study.

The purpose of the present study was to establish an optimal colon preparation for persons with diabetes who are undergoing colonoscopies. Specifically, the aim was to compare the difference between an experimental and standard preparation. Adequacy of bowel preparation is critical for good bowel visualization. Compared with nondiabetic patients, persons with diabetes have slower gastric emptying, colonic transit, and colon evacuation. Inadequate preparations may lead to suboptimal colonoscopy resulting in overlooked pathology, repeated examinations with associated risks, and organizational inefficiencies. Using a single-blind experimental design, 198 persons with diabetes who were scheduled to receive colonoscopies were randomly assigned to either the experimental (diabetic colon preparation) or the control (standard colon preparation) group. Patients in the diabetic colon preparation group had 70% good colon preparations compared with 54% in the standard group, and this finding was significant (χ = 5.14, p = 0.02). Results indicate that diabetic patients receiving 10 ounces of magnesium citrate 2 days prior to their colonoscopies followed by 10 ounces of magnesium citrate and 4-L polyethylene glycol the day prior to the procedure had cleaner colons than those receiving standard preparation of 10 ounces of magnesium citrate and 4-L polyethylene glycol the day prior to procedure. This colon preparation is safe, feasible, well-tolerated, and effective.

Risk factors for self-reported exercise-related leg pain in high school cross-country athletes.

CONTEXT: Prevention of exercise-related leg pain (ERLP) has not been successful because ERLP risk factors are not well known. OBJECTIVE: To determine the percentage of high school cross-country (XC) athletes who reported a history of ERLP in their running careers, to identify the percentage of athletes who reported an occurrence of ERLP during 1 XC season, and to investigate the association of selected factors (age, high school year, years of high school running, sex, ERLP history, body mass index [BMI], foot type, and training distance) and the occurrence of ERLP. DESIGN: Prospective cohort study. SETTING: Six local high schools. PATIENTS OR OTHER PARTICIPANTS: One hundred twenty-five high school XC athletes (62 females, 63 males). MAIN OUTCOME MEASURE(S): All athletes completed an initial ERLP questionnaire, and foot type was visually assessed. After the season, athletes were asked to complete a Web-based questionnaire regarding the seasonal occurrence of ERLP. Statistical analyses of differences (t tests) and associations (chi(2), relative risk) were conducted. RESULTS: A total of 103 of the 125 athletes (82.4%) reported a history of ERLP, with 81 athletes reporting ERLP occurrence within the month preceding completion of the initial questionnaire. Bilateral medial leg pain was the most common ERLP presentation. More than half of the athletes (58.4%) with an ERLP history reported that the pain had interfered with XC participation. Ninety-three athletes responded to the postseason questionnaire, and 45 (48.0%) reported ERLP seasonal occurrence. Most athletes (97.8%) who experienced the seasonal occurrence of ERLP had a history of ERLP. No associations were noted between ERLP history or seasonal occurrence and age, high school year, years of high school running, sex, BMI, foot type, or training distance. CONCLUSIONS: Both a history of ERLP and the seasonal occurrence of ERLP were common among these XC athletes. The only risk factor identified for ERLP season occurrence was ERLP history.