Hip load capacity cut-points for Astronaut Skeletal Health NASA Finite Element Strength Task Group Recommendations.

Concerns raised at a 2010 Bone Summit held for National Aeronautics and Space Administration Johnson Space Center led experts in finite element (FE) modeling for hip fracture prediction to propose including hip load capacity in the standards for astronaut skeletal health. The current standards for bone are based upon areal bone mineral density (aBMD) measurements by dual X-ray absorptiometry (DXA) and an adaptation of aBMD cut-points for fragility fractures. Task Group members recommended (i) a minimum permissible outcome limit (POL) for post-mission hip bone load capacity, (ii) use of FE hip load capacity to further screen applicants to astronaut corps, (iii) a minimum pre-flight standard for a second long-duration mission, and (iv) a method for assessing which post-mission physical activities might increase an astronaut's risk for fracture after return. QCT-FE models of eight astronaut were analyzed using nonlinear single-limb stance (NLS) and posterolateral fall (NLF) loading configurations. QCT data from the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort and the Rochester Epidemiology Project were analyzed using identical modeling procedures. The 75th percentile of NLS hip load capacity for fractured elderly males of the AGES cohort (9537N) was selected as a post-mission POL. The NLF model, in combination with a Probabilistic Risk Assessment tool, was used to assess the likelihood of exceeding the hip load capacity during post-flight activities. There was no recommendation to replace the current DXA-based standards. However, FE estimation of hip load capacity appeared more meaningful for younger, physically active astronauts and was recommended to supplement aBMD cut-points.

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy.

OBJECTIVE: The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe). METHODS: Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle. RESULTS: Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min-1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015). CONCLUSIONS: Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake. OBJECTIVE: We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk. DESIGN: Osteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression. RESULTS: In men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98). CONCLUSIONS: Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex.

Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health.

BACKGROUND: Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Nonpharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies. METHODS: The VIBES (Vibration to Improve Bone Density in Elderly Subjects) study is a randomized, double-blind, sham-controlled trial of the efficacy of low magnitude, high frequency mechanical stimulation in 200 men and women aged 60 years and older with bone mineral density T-scores by dual X-ray absorptiometry between -1 and -2.5 at entry. Participants are healthy, cognitively intact residents of independent living communities in the Boston area who receive free calcium and Vitamin D supplements. They are randomly assigned to active or sham treatment and stand on their assigned platform once daily for 10 min. All platforms have adherence data collection software downloadable to a laptop computer. Adverse events are closely monitored. 174 participants were randomized and will be followed for 2 years. Almost all active subjects have attained 1 year of follow-up. Bone mineral density is measured by both dual X-ray absorptiometry and quantitative computed tomography at baseline and annually. The main analysis will compare mean changes from baseline in volumetric bone density by quantitative computed tomography in active and sham groups. Adherence and treatment effect magnitude will also be evaluated. Secondary analyses will compare changes in two biochemical markers of bone turnover as well as longitudinal comparisons of muscle and balance endpoints. RESULTS: The VIBES trial has completed its first year of data collection and encountered multiple challenges leading to valuable lessons learned about the areas of recruitment from independent living communities, deployment of multiuser mechanical devices using radio frequency identification cards and electronic adherence monitoring, organization of transportation for imaging at a central site, and the expansion of study aims to include additional musculoskeletal outcomes. CONCLUSIONS: These lessons will guide future investigations in studies of individuals of advanced age.

Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate.

BACKGROUND: Anabolic responsiveness to teriparatide can be blunted or delayed in patients previously treated with alendronate. The extent of this effect is different for other antiresorptives. This study evaluated the early anabolic effects of teriparatide in postmenopausal women with osteoporosis previously treated with alendronate or risedronate. METHODS: Patients treated for at least 24 months with alendronate or risedronate discontinued their bisphosphonate and received teriparatide for 12 months. The primary endpoint was a comparison of changes from baseline in N-terminal propeptide of type 1 collagen after 3 months between prior bisphosphonate groups. We also examined changes in other bone turnover markers, bone mineral density (BMD), and relationships between early changes in bone turnover markers and 12-month areal and volumetric BMD. RESULTS: In the prior risedronate group, the N-terminal propeptide of type 1 collagen increase was significantly greater after 3 months of teriparatide than in the prior alendronate group (mean +/- se, 86.0 +/- 5.6 vs. 61.2 +/- 5.3 ng/ml, respectively; P < 0.001). Findings were similar for the other bone turnover markers. The changes in areal BMD and trabecular spine volumetric BMD were also greater in the prior risedronate group (P < 0.05). Early changes in bone turnover markers correlated with changes in trabecular spine volumetric BMD at 12 months (Spearman r = 0.45). Teriparatide was well tolerated. CONCLUSION: This nonrandomized but prospective study suggests that there may be differences in anabolic responsiveness to teriparatide as a function of the type of prior bisphosphonate exposure.

Prehospital analgesia with acupressure at the Baihui and Hegu points in patients with radial fractures: a prospective, randomized, double-blind trial.

BACKGROUND: Pain during transportation is a common phenomenon in emergency medicine. As acupressure has been deemed effective for pain management by the National Institutes of Health, we conducted a study to evaluate its effectiveness in prehospital patients with isolated distal radial fracture. METHODS: This was a prospective, randomized, double-blind study. Thirty-two patients were enrolled. Acupressure was performed either at "true" points or at "sham" points. Vital signs and pain and anxiety scores were recorded before and after the acupressure treatment. Normally distributed values were compared using the Student t test. RESULTS: Pretreatment scores for pain and anxiety were similar in the 2 groups (47.6 +/- 8.9 vs 51.2 +/- 8.7 visual analog scale [VAS] score for pain, 52.4 +/- 6.0 vs 47.5 +/- 9.3 VAS score for anxiety). At the hospital, patients in the true-points group had significantly lower pain (36.6 +/- 11.0 vs 56.0 +/- 13.3 VAS score, P < .001) and anxiety scores (34.9 +/- 22.2 vs 53.4 +/- 19.7 VAS score, P = .022). CONCLUSION: Acupressure in the prehospital setting effectively reduces pain and anxiety in patients with distal radial trauma.

Auricular acupressure as a treatment for anxiety before extracorporeal shock wave lithotripsy in the elderly.

PURPOSE: Auricular acupuncture at the relaxation point has been shown to be effective treatment for anxiety. We hypothesized that auricular acupressure may decrease anxiety in elderly individuals who are transported by ambulance before receiving ESWL. MATERIALS AND METHODS: We enrolled 100 patients with renal calculi who were transported to the local hospital by special ambulance, accompanied by 2 paramedics. Paramedic 1 performed data collection, while paramedic 2 performed auricular acupressure in patients randomly assigned to a relaxation group and a sham treated group. Anxiety was measured using a visual analog scale score on a scale of 0 to 100 mm. RESULTS: Each group consisted of 50 patients with similar demographic characteristics. The relaxation group had significantly decreased anxiety scores upon arrival at the hospital and lower anticipation of pain scores (mean+/-SD 57.6+/-21.8 to 15.4+/-9.8 and 35.7+/-29.7 to 9.5+/-4.1 mm VAS) than the sham treated group (55.5+/-25.9 to 49.8+/-28.9 and 37.7+/-24.1 to 33.8+/-25.2 mm VAS, respectively, 2-way repeated measure ANOVA each p=0.001). Estimated waiting times for treatment did not differ significantly between the 2 groups (5.0+/-2.5 and 5.5+/-2.95, respectively, repeated measures ANOVA p=0.83). The Post-Intervention Anxiety visual analog scale demonstrated the significant superiority of the true treatment group (19.5+/-5.9 and 66.8+/-27.9 mm VAS, respectively, p=0.001). CONCLUSIONS: Elderly patients who received auricular acupressure at specific relaxation points while being transported to the hospital were less anxious, anticipated less pain and were more optimistic about the outcome of treatment that they will receive than the sham treated group. These data prove that this is an effective treatment for anxiety that improves the patient overall perception of ESWL.

The influence of stellate ganglion transcutaneous electrical nerve stimulation on signal quality of pulse oximetry in prehospital trauma care.

BACKGROUND: Accurate monitoring of the peripheral arterial oxygen saturation has become an important tool in the prehospital emergency medicine. This monitoring requires an adequate plethysmographic pulsation. Signal quality is diminished by cold ambient temperature due to vasoconstriction. Blockade of the stellate ganglion can improve peripheral vascular perfusion and can be achieved by direct injection or transcutaneous electrical nerve stimulation (TENS) stimulation. We evaluated whether TENS on the stellate ganglion would reduce vasoconstriction and thereby improve signal detection quality of peripheral pulse oximetry. METHODS: In our study, 53 patients with minor trauma who required transport to the hospital were enrolled. We recorded vital signs, including core and skin temperature before and after transport to the hospital. Pulse oximetry sensors were attached to the patient's second finger on both hands. TENS of the stellate ganglion was started on one side after the beginning of the transport. Pulse oximeter alerts, due to poor signal detection, were recorded for each side separately. RESULTS: On the hand treated with TENS we detected a significant reduction of alerts compared to the other side (mean alerts TENS 3.1 [1-15] versus control side 8.8 [1-28] P < 0.05). The duration of dropouts was shorter as well (mean duration TENS 77 [16-239] s versus control side 333 [78-1002] s). CONCLUSION: The data indicate that blockade of the stellate ganglion with TENS improves signal quality of pulse oximeters in the prehospital setting.

TENS relieves acute posttraumatic hip pain during emergency transport.

BACKGROUND: In Central Europe, ambulances for patients suffering from pain caused by nonlife-threatening trauma, such as hip fractures are staffed by medical personnel (medics) without physicians. Thus, there is an urgent need for nonpharmacological interventions that can be applied during the transport by basic life-support (BLS) medical personnel. METHODS: In all, 101 patients were screened for participation in this randomized placebo-controlled double-blind study, and randomly assigned to two groups (verum and sham transcutaneous electrical nerve stimulation [TENS]). First, medic A recorded all baseline parameters and measurements, then medic B performed TENS in absence of medic A. At the end of transportation, medic A performed data collection. Each patient was asked to grade his/her pain and anxiety level on visual analog scales (VAS, 0 to 100 mm). RESULTS: From 101 screened patients fulfilling the entry criteria, 29 declined consent and 9 had to be excluded from the analysis because of their final diagnosis. Therefore, the data from 30 patients (group 1, verum TENS) as well as from 33 patients (group 2 [control], sham TENS) were analyzed. No significant differences in potentially influencing factors were found before treatment. Pain scores upon arrival at the hospital differed significantly between group 1 and group 2 (p < 0.01). In group 1, pain reduction was observed between departure from the site of emergency and arrival at the hospital (VAS: 89 +/- 9 to 59 +/- 6 mm), whereas pain scores remained nearly unchanged in group 2 (VAS: 86 +/- 12 to 79 +/- 11 mm). CONCLUSION: Our findings show that TENS is a valuable and fast-acting pain treatment under the difficult circumstances of "out-of-hospital rescue". Because of its lack of side effects, it could also be a valuable tool in the hospital.

Transcutaneous electrical nerve stimulation: an effective treatment for pain caused by renal colic in emergency care.

PURPOSE: Acute renal colic is one of the most anguishing forms of pain in humans. We hypothesized that TENS is an effective pain treatment in patients with acute renal colic. MATERIALS AND METHODS: A total of 100 patients with acute flank pain and suspected renal colic consented to participate in our study. Paramedic 1 recorded baseline parameters at the emergency site and at the end of transportation. Paramedic 2 performed TENS in patients randomly assigned to G1 with actual TENS or to G2 with sham TENS. Pain and anxiety were measured using paper based visual analog scales on a scale of 0 to 100 mm. RESULTS: Of 100 screened patients 73 had renal colic, including 39 in G1 and 34 in G2. There was no significant difference with regard to potentially influencing factors, such as patient age, sex, weight, height, blood pressure and heart rate, pain, nausea and anxiety between the groups before treatment. G1 showed a significant mean pain decrease +/- SD of more than 50% (85.7 +/- 10.5 to 33.3 +/- 16.0 mm, p <0.01). G2 showed no variation in mean pain scores (85.8 +/- 18.0 to 82.6 +/- 14.3 mm). G1 showed changes in the mean anxiety score (69.0 +/- 8.4 to 37.7 +/- 15.1 mm, p <0.01), nausea score (90.7 +/- 9.2 to 44.9 +/- 22.0 mm) and heart rate (92 +/- 10 to 64 +/- 8 bpm), while G2 showed nonsignificant changes. CONCLUSIONS: This trial shows that local TENS is a rapid and effective treatment for renal colic pain. We found TENS to be a good nondrug therapy under the difficult circumstances of out of hospital rescue.

Treatment with raloxifene for 2 years increases vertebral bone mineral density as measured by volumetric quantitative computed tomography.

Volumetric quantitative computed tomography (vQCT), using multiple thin-slice acquisition, measures three-dimensional volumetric bone mineral density (BMD, mg/cm3). vQCT is often used to measure BMD of lumbar vertebrae and may detect early changes in trabecular, cortical, or integral BMD that extend beyond the technical limits of areal dual X-ray absorptiometry (DXA) BMD measurements. The objective of this study was to determine the effect of 2 years of raloxifene (RLX) treatment on several volumetric BMD measures in a subset of postmenopausal women (n=58) enrolled in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Patients in this study were randomized to one of three treatment groups: placebo (n=21), RLX 60 mg/day (n=17), or RLX 120 mg/day (n=20), and all patients received daily calcium (500 mg) and vitamin D (400-600 IU) supplementation. Data from the raloxifene treatment groups were pooled for each analysis. Following 2 years of raloxifene treatment, there was a significant percent change from baseline in the vQCT regions of interest (ROIs) of midintegral BMD, total trabecular BMD, and total integral BMD (P<0.05) compared to placebo, while there was no significant change in the spinal DXA BMD measurement. These data provide the first longitudinal assessment by vQCT of changes in vertebral bone density after 2 years of treatment with raloxifene. vQCT appears to be a valuable technique for measuring the effects of raloxifene treatment in this population of postmenopausal women with osteoporosis.

Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity.

UNLABELLED: BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX-2 selective NSAIDs with aspirin (COX-2/ASA) compared with nonusers. This suggests a role for COX-2/ASA in osteoporosis. INTRODUCTION: The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway. MATERIALS AND METHODS: NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men: 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of > 1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of < 1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status. RESULTS: After adjustment for possible confounders, current use of relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2-7.3 CI) and total hip (4.6%, 0.5-8.8 CI) by DXA and at both trabecular (34.1%, 15.4-52.7 CI) and cortical spine (12.8%, 2.3-23.3 CI) by quantitative computed tomography. CONCLUSIONS: Our data suggest that the combination of relative COX-2 selective NSAIDs and aspirin is associated with higher BMD at multiple skeletal sites in men and women.

Treatment of Crigler-Najjar type 1 disease: relevance of early liver transplantation.

BACKGROUND: Crigler-Najjar syndrome type 1 (CNS1) is characterized by severe unconjugated hyperbilirubinemia from birth, caused by total failure of UDP-glucuronyltransferase activity. Only orthotopic liver transplantation (OLT) offers the prospect of cure. However, because the onset of neurologic deficits is unpredictable, timing of OLT remains difficult. METHODS: In our transplant center, 3 patients underwent early OLT for CNS1. Two of them (7 yr, 12 yr) showed mild to moderate neurologic deficits only few weeks before OLT, another patient (4 yr) had no signs of bilirubin encephalopathy. All patients required extensive phototherapy to control bilirubin levels. Thus, OLT was performed shortly after the onset of neurologic symptoms or as a prophylactic procedure, respectively. RESULTS: OLT was uneventful in all recipients. One of the symptomatic patients (7 yr) completely recovered from neurologic deficits at 36 months on OLT, whereas the other patient (12 yr) significantly improved symptoms at 27 months of OLT. These patients, including the 4-year-old boy, attend school at appropriate grades now. CONCLUSIONS: Irreversible brain damage (kernicterus) may occur in the course of CNS1 disease. Because no alternative treatment options are available at this time, OLT should be performed as a preventive procedure to counteract severe CNS-related complications.

Successful liver transplantation of two brothers with crigler-najjar syndrome type 1 using a single cadaveric organ.

Crigler-Najjar type 1 disease (CNS1) is the result of a genetic defect, leading to complete functional loss of an enzyme which glucuronidates bilirubin. As a consequence, unconjugated bilirubin accumulates and may cause kernicterus, the most serious complication in adolescents. Phototherapy effectively adjusts bilirubin levels less than critical concentrations over many years but become less effective in elder children. Therefore, liver transplantation must be performed as definite therapy in these patients to avoid irreversible neurological deficits. Two brothers with CNS1, one without neurological deficits and one with moderate brain injury underwent orthotopic split liver transplantation from the same donor. The intra- and postoperative course of both patients was uneventful. Bilirubin levels normalized after transplantation in both recipients. Furthermore, mental and physical development considerably improved upon transplantation in the brother with neurological dysfunction. Therefore, orthotopic liver transplantation in CNS1 patients should be performed early enough to avoid irreversible brain damage, i.e., as a prophylactic procedure.