A 0.05 m Change in Inertial Measurement Unit Placement Alters Time and Frequency Domain Metrics during Running.

Inertial measurement units (IMUs) provide exciting opportunities to collect large volumes of running biomechanics data in the real world. IMU signals may, however, be affected by variation in the initial IMU placement or movement of the IMU during use. To quantify the effect that changing an IMU's location has on running data, a reference IMU was 'correctly' placed on the shank, pelvis, or sacrum of 74 participants. A second IMU was 'misplaced' 0.05 m away, simulating a 'worst-case' misplacement or movement. Participants ran over-ground while data were simultaneously recorded from the reference and misplaced IMUs. Differences were captured as root mean square errors (RMSEs) and differences in the absolute peak magnitudes and timings. RMSEs were ≤1 g and ~1 rad/s for all axes and misplacement conditions while mean differences in the peak magnitude and timing reached up to 2.45 g, 2.48 rad/s, and 9.68 ms (depending on the axis and direction of misplacement). To quantify the downstream effects of these differences, initial and terminal contact times and vertical ground reaction forces were derived from both the reference and misplaced IMU. Mean differences reached up to -10.08 ms for contact times and 95.06 N for forces. Finally, the behavior in the frequency domain revealed high coherence between the reference and misplaced IMUs (particularly at frequencies ≤~10 Hz). All differences tended to be exaggerated when data were analyzed using a wearable coordinate system instead of a segment coordinate system. Overall, these results highlight the potential errors that IMU placement and movement can introduce to running biomechanics data.

Increasing Step Rate Reduces Peak and Cumulative Insole Force in Collegiate Runners.

PURPOSE: The primary goal of this study was to examine changes in peak insole force and cumulative weighted peak force (CWPF)/km with increased step rate in collegiate runners. The secondary goal was to determine whether sacral acceleration correlates with insole force when increasing step rate. METHODS: Twelve collegiate distance runners ran 1000 m outdoors at 3.83 m·s -1 at preferred and 10% increased step rates while insole force and sacral acceleration were recorded. Cumulative weighted peak force/km was calculated from insole force based on cumulative damage models. The effects of step rate on peak insole force and CWPF·km -1 were tested using paired t tests or Wilcoxon tests. Correlation coefficients between peak axial (approximately vertical) sacral acceleration times body mass and peak insole force were calculated on cohort and individual levels. RESULTS: Peak insole force and CWPF·km -1 decreased ( P < 0.001) with increased step rate. Peak axial sacral acceleration did not correlate with peak insole force on the cohort level ( r = 0.35, P = 0.109) but did within individuals (mean, r = 0.69-0.78; P < 0.05). CONCLUSIONS: Increasing step rate may reduce peak vGRF and CWPF·km -1 in collegiate runners. Therefore, clinicians should consider step rate interventions to reduce peak and cumulative vGRF in this population. Individual-specific calibrations may be required to assess changes in peak vGRF in response to increasing step rate using wearable accelerometers.

Acceleration-Based Estimation of Vertical Ground Reaction Forces during Running: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

Twenty-seven methods of estimating vertical ground reaction force first peak, loading rate, second peak, average, and/or time series from a single wearable accelerometer worn on the shank or approximate center of mass during running were compared. Force estimation errors were quantified for 74 participants across different running surfaces, speeds, and foot strike angles and biases, repeatability coefficients, and limits of agreement were modeled with linear mixed effects to quantify the accuracy, reliability, and precision. Several methods accurately and reliably estimated the first peak and loading rate, however, none could do so precisely (the limits of agreement exceeded ±65% of target values). Thus, we do not recommend first peak or loading rate estimation from accelerometers with the methods currently available. In contrast, the second peak, average, and time series could all be estimated accurately, reliably, and precisely with several different methods. Of these, we recommend the 'Pogson' methods due to their accuracy, reliability, and precision as well as their stability across surfaces, speeds, and foot strike angles.

Hoof Expansion, Deformation, and Surface Strains Vary with Horseshoe Nail Positions.

Racehorses are susceptible to underrun heel hoof conformation. Racehorses are often shod with nails placed toward the heel. It is unknown if palmar nails restrict or alter hoof deformation in a manner that could promote the development of underrun heel conformation over time with repeated loading. To determine how the addition of palmar nails affects heel deformation during limb loading, hoof expansion and hoof wall deformations were quantified using rosette strain gauges and kinematic markers during in the vitro limb loading of cadaveric limbs that simulated midstance for walk, trot, and canter loads. Nail treatments used to attach a horseshoe to the hoof included: toe nails (T), toe and quarter nails (TQ), and toe, quarter, and heel nails (TQH). The effects of nail treatment on heel expansion and hoof wall deformations were assessed using repeated measures analysis of variance (p < 0.05). Nails placed palmar to the quarters of the hoof decreased heel expansion (p < 0.001). Heel nails resulted in the largest changes in hoof wall principal strain directions distally. The application of nails palmar to the hoof quarters alters hoof wall deformation during limb loading. The continued loading of the hoof with palmer nails could alter hoof conformation over time.

Unsupervised Gait Event Identification with a Single Wearable Accelerometer and/or Gyroscope: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

We evaluated 18 methods capable of identifying initial contact (IC) and terminal contact (TC) gait events during human running using data from a single wearable sensor on the shank or sacrum. We adapted or created code to automatically execute each method, then applied it to identify gait events from 74 runners across different foot strike angles, surfaces, and speeds. To quantify error, estimated gait events were compared to ground truth events from a time-synchronized force plate. Based on our findings, to identify gait events with a wearable on the shank, we recommend the Purcell or Fadillioglu method for IC (biases +17.4 and -24.3 ms; LOAs -96.8 to +131.6 and -137.0 to +88.4 ms) and the Purcell method for TC (bias +3.5 ms; LOAs -143.9 to +150.9 ms). To identify gait events with a wearable on the sacrum, we recommend the Auvinet or Reenalda method for IC (biases -30.4 and +29.0 ms; LOAs -149.2 to +88.5 and -83.3 to +141.3 ms) and the Auvinet method for TC (bias -2.8 ms; LOAs -152.7 to +147.2 ms). Finally, to identify the foot in contact with the ground when using a wearable on the sacrum, we recommend the Lee method (81.9% accuracy).

An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well.

Accelerometer-based prediction of running injury in National Collegiate Athletic Association track athletes.

Running-related injuries (RRI) may result from accumulated microtrauma caused by combinations of high load magnitudes (vertical ground reaction forces; vGRFs) and numbers (strides). Yet relationships between vGRF and RRI remain unclear - potentially because previous research has largely been constrained to collecting vGRFs in laboratory settings and ignoring relationships between RRI and stride number. In this preliminary proof-of-concept study, we addressed these constraints: Over a 60-day period, each time collegiate athletes (n = 9) ran they wore a hip-mounted activity monitor that collected accelerations throughout the entire run. Accelerations were used to estimate peak vGRF, number of strides, and weighted cumulative loading (sum of peak vGRFs weighted to the 9th power) across the entirety of each run. Runners also reported their post-training pain/fatigue and any RRI that prevented training. Across 419 runs and >2.1 million strides, injured (n = 3) and uninjured (n = 6) participants did not report significantly different pain/fatigue (p = 0.56) or mean number of strides per run (p = 0.91). Injured participants did, however, have significantly greater peak vGRFs (p = 0.01) and weighted cumulative loading per run (p < 0.01). Results from this small but extensively studied sample of elite runners demonstrate that loading profiles (load magnitude-number combinations) quantified with activity monitors can provide valuable information that may prove essential for: (1) testing hypotheses regarding overuse injury mechanisms, (2) developing injury-prediction models, and (3) designing and adjusting athlete- and loading-specific training programs and feedback.

Hitting the ground running: Evaluating an integrated racehorse limb and race surface computational model.

Race surface mechanics contribute to musculoskeletal injury in racehorses. These mechanics affect ground reaction forces applied to the hoof, and thus limb motions during stance that can contribute to musculoskeletal pathologies. Race surface design has been largely empirical within the industry, with little uniform consensus for injury prevention and performance. Furthermore, race surface installations are too expensive to install experimentally. The objective of this research was to develop and evaluate an integrated racehorse limb and race surface computational model. Combined forward/inverse dynamic simulations of distal leading forelimb motions of a galloping horse during stance were compared to 2D distal leading forelimb kinematics of actual galloping racehorses on race surfaces with measured mechanics. Model predicted angular and translational kinematic profiles had similar qualitative shapes as experimental data, with comparable peak magnitudes. Model predictions of peak metacarpophalangeal position and timing were within 11° and 8ms of mean experimental data. The model overestimated peak fetlock angular velocity on consolidated surfaces (up to 1390°/s), and hoof displacements (up to 4cm) during stance. The model's ability to produce comparable qualitative kinematic profiles to experimental data and biologically reasonable fetlock and hoof motions support the future use of this model to explore the effect of race surface parameters on increasing or decreasing distal limb motions and provide supportive evidence for potential mechanisms of injury.

Feasibility of a dynamic web guidance approach for personalized physical activity prescription based on daily information from wearable technology.

BACKGROUND: Computer tailored, Web-based interventions have emerged as an effective approach to promote physical activity. Existing programs, however, do not adjust activities according to the participant's compliance or physiologic adaptations, which may increase risk of injury and program attrition in sedentary adults. To address this limitation, objective activity monitor (AM) and heart rate data could be used to guide personalization of physical activity, but improved Web-based frameworks are needed to test such interventions. OBJECTIVE: The objective of this study is to (1) develop a personalized physical activity prescription (PPAP) app that combines dynamic Web-based guidance with multi-sensor AM data to promote physical activity and (2) to assess the feasibility of using this system in the field. METHODS: The PPAP app was constructed using an open-source software platform and a custom, multi-sensor AM capable of accurately measuring heart rate and physical activity. A novel algorithm was written to use a participant's compliance and physiologic response to aerobic training (ie, changes in daily resting heart rate) recorded by the AM to create daily, personalized physical activity prescriptions. In addition, the PPAP app was designed to (1) manage the transfer of files from the AM to data processing software and a relational database, (2) provide interactive visualization features such as calendars and training tables to encourage physical activity, and (3) enable remote administrative monitoring of data quality and participant compliance. A 12-week feasibility study was performed to assess the utility and limitations of the PPAP app used by sedentary adults in the field. Changes in physical activity level and resting heart rate were monitored throughout the intervention. RESULTS: The PPAP app successfully created daily, personalized physical activity prescriptions and an interactive Web environment to guide and promote physical activity by the participants. The varied compliance of the participants enabled evaluation of administrative features of the app including the generation of automated email reminders, participation surveys, and daily AM file upload logs. CONCLUSIONS: This study describes the development of the PPAP app, a closed-loop technology framework that enables personalized physical activity prescription and remote monitoring of an individual's compliance and health response to the intervention. Data obtained during a 12-week feasibility study demonstrated the ability of the PPAP app to use objective AM data to create daily, personalized physical activity guidance, provide interactive feedback to users, and enable remote administrative monitoring of data quality and subject compliance. Using this approach, public health professionals, clinicians, and researchers can adapt the PPAP app to facilitate a range of personalized physical activity interventions to improve health outcomes, assess injury risk, and achieve fitness performance goals in diverse populations.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

BACKGROUND: The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women. METHODS: An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated. RESULTS: Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9). CONCLUSIONS: Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women. CLINICAL TRIALS REGISTRATION: NCT00825929.

Modeling equine race surface vertical mechanical behaviors in a musculoskeletal modeling environment.

Race surfaces have been associated with the incidence of racehorse musculoskeletal injury, the leading cause of racehorse attrition. Optimal race surface mechanical behaviors that minimize injury risk are unknown. Computational models are an economical method to determine optimal mechanical behaviors. Previously developed equine musculoskeletal models utilized ground reaction floor models designed to simulate a stiff, smooth floor appropriate for a human gait laboratory. Our objective was to develop a computational race surface model (two force-displacement functions, one linear and one nonlinear) that reproduced experimental race surface mechanical behaviors for incorporation in equine musculoskeletal models. Soil impact tests were simulated in a musculoskeletal modeling environment and compared to experimental force and displacement data collected during initial and repeat impacts at two racetracks with differing race surfaces - (i) dirt and (ii) synthetic. Best-fit model coefficients (7 total) were compared between surface types and initial and repeat impacts using a mixed model ANCOVA. Model simulation results closely matched empirical force, displacement and velocity data (Mean R(2)=0.930-0.997). Many model coefficients were statistically different between surface types and impacts. Principal component analysis of model coefficients showed systematic differences based on surface type and impact. In the future, the race surface model may be used in conjunction with previously developed the equine musculoskeletal models to understand the effects of race surface mechanical behaviors on limb dynamics, and determine race surface mechanical behaviors that reduce the incidence of racehorse musculoskeletal injury through modulation of limb dynamics.

Standardizing accelerometer-based activity monitor calibration and output reporting.

Wearable accelerometer-based activity monitors (AMs) are used to estimate energy expenditure and ground reaction forces in free-living environments, but a lack of standardized calibration and data reporting methods limits their utility. The objectives of this study were to (1) design an inexpensive and easily reproducible AM testing system, (2) develop a standardized calibration method for accelerometer-based AMs, and (3) evaluate the utility of the system and accuracy of the calibration method. A centrifuge-type device was constructed to apply known accelerations (0-8g) to each sensitive axis of 30 custom and two commercial AMs. Accelerometer data were recorded and matrix algebra and a least squares solution were then used to determine a calibration matrix for the custom AMs to convert raw accelerometer output to units of g's. Accuracy was tested by comparing applied and calculated accelerations for custom and commercial AMs. AMs were accurate to within 4% of applied accelerations. The relatively inexpensive AM testing system (< $100) and calibration method has the potential to improve the sharing of AM data, the ability to compare data from different studies, and the accuracy of AM-based models to estimate various physiological and biomechanical quantities of interest in field-based assessments of physical activity.

Ground reaction force estimates from ActiGraph GT3X+ hip accelerations.

Simple methods to quantify ground reaction forces (GRFs) outside a laboratory setting are needed to understand daily loading sustained by the body. Here, we present methods to estimate peak vertical GRF (pGRFvert) and peak braking GRF (pGRFbrake) in adults using raw hip activity monitor (AM) acceleration data. The purpose of this study was to develop a statistically based model to estimate pGRFvert and pGRFbrake during walking and running from ActiGraph GT3X+ AM acceleration data. 19 males and 20 females (age 21.2 ± 1.3 years, height 1.73 ± 0.12 m, mass 67.6 ± 11.5 kg) wore an ActiGraph GT3X+ AM over their right hip. Six walking and six running trials (0.95-2.19 and 2.20-4.10 m/s, respectively) were completed. Average of the peak vertical and anterior/posterior AM acceleration (ACCvert and ACCbrake, respectively) and pGRFvert and pGRFbrake during the stance phase of gait were determined. Thirty randomly selected subjects served as the training dataset to develop generalized equations to predict pGRFvert and pGRFbrake. Using a holdout approach, the remaining 9 subjects were used to test the accuracy of the models. Generalized equations to predict pGRFvert and pGRFbrake included ACCvert and ACCbrake, respectively, mass, type of locomotion (walk or run), and type of locomotion acceleration interaction. The average absolute percent differences between actual and predicted pGRFvert and pGRFbrake were 8.3% and 17.8%, respectively, when the models were applied to the test dataset. Repeated measures generalized regression equations were developed to predict pGRFvert and pGRFbrake from ActiGraph GT3X+ AM acceleration for young adults walking and running. These equations provide a means to estimate GRFs without a force plate.

Evaluation of an exercise field test using heart rate monitors to assess cardiorespiratory fitness and heart rate recovery in an asymptomatic population.

PURPOSE: Measures of cardiorespiratory fitness (CRF) and heart rate recovery (HRR) can improve risk stratification for cardiovascular disease, but these measurements are rarely made in asymptomatic individuals due to cost. An exercise field test (EFT) to assess CRF and HRR would be an inexpensive method for cardiovascular disease risk assessment in large populations. This study assessed 1) the predictive accuracy of a 12-minute run/walk EFT for estimating CRF ([Formula: see text]) and 2) the accuracy of HRR measured after an EFT using a heart rate monitor (HRM) in an asymptomatic population. METHODS: Fifty subjects (48% women) ages 18-45 years completed a symptom-limited exercise tolerance test (ETT) (Bruce protocol) and an EFT on separate days. During the ETT, [Formula: see text] was measured by a metabolic cart, and heart rate was measured continuously by a HRM and a metabolic cart. RESULTS: EFT distance and sex independently predicted[Formula: see text]. The average absolute difference between observed and predicted [Formula: see text] was 0.26 ± 3.27 ml·kg-1·min-1 for our model compared to 7.55 ± 3.64 ml·kg-1·min-1 for the Cooper model. HRM HRR data were equivalent to respective metabolic cart values during the ETT. HRR at 1 minute post-exercise during ETT compared to the EFT had a moderate correlation (r=0.75, p<0.001). CONCLUSION: A more accurate model to estimate CRF from a 12-minute run/walk EFT was developed, and HRR can be measured using a HRM in an asymptomatic population outside of clinical settings.

The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women.

OBJECTIVE: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. DESIGN: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. METHODS: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. RESULTS: Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was less than 200  copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSION: Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission.

Estimating youth locomotion ground reaction forces using an accelerometer-based activity monitor.

To address a variety of questions pertaining to the interactions between physical activity, musculoskeletal loading and musculoskeletal health/injury/adaptation, simple methods are needed to quantify, outside a laboratory setting, the forces acting on the human body during daily activities. The purpose of this study was to develop a statistically based model to estimate peak vertical ground reaction force (pVGRF) during youth gait. 20 girls (10.9 ± 0.9 years) and 15 boys (12.5 ± 0.6 years) wore a Biotrainer AM over their right hip. Six walking and six running trials were completed after a standard warm-up. Average AM intensity (g) and pVGRF (N) during stance were determined. Repeated measures mixed effects regression models to estimate pVGRF from Biotrainer activity monitor acceleration in youth (girls 10-12, boys 12-14 years) while walking and running were developed. Log transformed pVGRF had a statistically significant relationship with activity monitor acceleration, centered mass, sex (girl), type of locomotion (run), and locomotion type-acceleration interaction controlling for subject as a random effect. A generalized regression model without subject specific random effects was also developed. The average absolute differences between the actual and predicted pVGRF were 5.2% (1.6% standard deviation) and 9% (4.2% standard deviation) using the mixed and generalized models, respectively. The results of this study support the use of estimating pVGRF from hip acceleration using a mixed model regression equation.

Identifying factors related to Achilles tendon stress, strain, and stiffness before and after 6 months of growth in youth 10-14 years of age.

The purposes of this study were (1) determine if youth peak Achilles tendon (AT) strain, peak AT stress, and AT stiffness, measured during an isometric plantar flexion, differed after six months (mos) of growth, and (2) determine if sex, physical activity level (Physical Activity Questionnaire (PAQ-C)), and/or growth rate (GR) were related to these properties. AT stress, strain, and stiffness were quantified in 20 boys (13.47±0.81 years) and 22 girls (11.18±0.82 years) at 2 times (0 and 6 mos). GR (change in height in 6 mos) was not significantly different between boys and girls (3.5±1.4 and 3.4±1.1cm/6 mos respectively). Peak AT strain and stiffness (mean 3.8±0.4% and 128.9±153.6N/mm, respectively) did not differ between testing sessions or sex. Peak AT stress (22.1±2.4 and 24.0±2.1MPa at 0 and 6 mos, respectively) did not differ between sex and increased significantly at 6 mos due to a significant decrease in AT cross-sectional area (40.6±1.3 and 38.1±1.6mm(2) at 0 and 6 mos, respectively) with no significant difference in peak AT force (882.3±93.9 and 900.3± 65.5N at 0 and 6 mos, respectively). Peak AT stress was significantly greater in subjects with greater PAQ-C scores (9.1% increase with 1 unit increase in PAQ-C score) and smaller in subjects with faster GRs (13.8% decrease with 1cm/6 mos increase in GR). These results indicate that of the AT mechanical properties quantified, none differed between sex, and only peak AT stress significantly differed after 6 months and was related to GR and physical activity.

When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery?

BACKGROUND: HAART dramatically reduces mother-to-child transmission of HIV allowing vaginal delivery if the viral load is low. This study provides data for the optimum timing of short-term HAART in pregnancy. METHODS: Retrospective multicentre cohort study of pregnant women commencing HAART in London and Brighton, UK. Demographics, gestation, drug class, CD4 cell count, and viral load results were collated. Survival curves for reaching a viral load less than 50  copies/ml were stratified by initial HIV viral load. Cox's proportional hazards regression model was adjusted for demographics and immunovirological parameters. RESULTS: Viral load was less than 50  copies/ml in 292 of 378 pregnancies (77.2%) by delivery. Pretreatment viral load was associated with the time taken, and the proportion achieving a viral load less than 50  copies/ml at (P≤0.001). When baseline viral load was less than 10 ,000  copies/ml, gestational age at HAART initiation did not affect success up to 26.3 weeks gestation. When viral load was more than 10 ,000  copies/ml, deferring HAART past 20.4 weeks reduced the probability of reaching less than 50  copies/ml by delivery (P=0.011). When baseline viral load was more than 100, 000  copies/ml the likelihood of reaching a viral load of less than 50  copies/ml was low (37%: hazard ratio 0.31), and dependent on the length of time on HAART. The hazard ratio for a nonnucleoside reverse transcriptase inhibitor regimen achieving a viral load less than 50  copies/ml compared with a protease inhibitor was 0.7 (95% confidence interval 0.52-0.94). CONCLUSION: With a viral load more than 10, 000  copies/ml and especially with a viral load more than 100 ,000  copies/ml, the probability of achieving either less than 50 copies/ml by the time of delivery is compromised by delaying initiation of short-term highly active antiretroviral therapy beyond 20.4 weeks gestation. Current UK and other guidelines for when to commence START may therefore limit the chance of vaginal delivery.

Pregnant women with HIV infection can expect healthy survival: three-year follow-up.

OBJECTIVES: To document postpartum disease-free survival of HIV-infected women taking antiretroviral therapy (ART) during pregnancy. METHODS: Laboratory and clinical data were collected on all HIV-infected pregnant women delivering from 1998 to 2002 and followed up until September 2004 at 6 hospitals in London. Mothers were grouped according to receipt of zidovudine monotherapy (ZDVm), highly active antiretroviral therapy (HAART) given during and continued after pregnancy (cHAART), and short-term HAART given during pregnancy and discontinued on delivery (START). RESULTS: Eight-five women took ZDVm, 155 took cHAART, and 71 took START. The mean follow-up for all mothers was 33 months, with a total of 847 person-years. At the first antenatal clinic (ANC) visit, 72% of women were in Centers for Disease Control and Prevention (CDC) stage A, 85% were treatment naive, and the ZDVm group had a median HIV viral load (VL) 10-fold less than those mothers who started HAART during pregnancy. At last follow-up, 1 patient had died and 6 (1.9%) had progressed to CDC stage C; 62% of all women, including a quarter of the ZDVm group, were receiving HAART for their own health; and 83% of all mothers had a VL <50 HIV RNA copies/mL of plasma regardless of whether they were on treatment or not. CONCLUSIONS: The median-term postpartum prognosis of HIV-infected pregnant women with access to HAART is good. Exposure to short-course ZDVm or START during pregnancy did not jeopardize their response to subsequent therapy.