Supervised exercise therapy for intermittent claudication in a community-based setting is as effective as clinic-based

ObjectiveThis cohort study was conducted to determine the effect on walking distances of supervised exercise therapy provided in a community-based setting.MethodsThe study included all consecutive patients presenting at the vascular outpatient clinic with intermittent claudication, diagnosed by a resting ankle brachial index <0.9, who had no previous peripheral vascular intervention for peripheral arterial disease, no major amputation, and sufficient command of the Dutch language. The exclusion criterion was the inability to walk the baseline treadmill test for a minimum of 10 m. The intervention was a supervised exercise therapy in a community-based setting. A progressive treadmill test at baseline and at 1, 3, and 6 months of follow-up measured initial claudication distance and absolute claudication distance. Changes were calculated using the mean percentages of change.ResultsFrom January through October 2005, 93 consecutive patients with claudication were eligible. Overall, 37 patients discontinued the supervised exercise therapy program. Eleven stopped because of intercurrent diseases, whereas for 10, supervised exercise therapy did not lead to adequate improvement and they underwent a vascular intervention. Three patients quit the program, stating that they were satisfied with the regained walking distance and did not require further supervised exercise therapy. Ten patients were not motivated sufficiently to continue the program, and in three patients, a lack of adequate insurance coverage was the reason for dropping out. Data for 56 patients were used and showed a mean percentage increase in initial claudication distance of 187% after 3 months and 240% after 6 months. The mean percentage of the absolute claudication distance increased 142% after 3 months and 191% after 6 months.ConclusionSupervised exercise therapy in a community-based setting is a promising approach to providing conservative treatment for patients with intermittent claudication

Meteorite search in the deflation basins in Lea County, New Mexico and Winkler County, Texas, USA: Discovery of Lea County 003 (H4)

During the past few decades great numbers of meteorites have been recovered from the ice accumulation zones of Antarctica and from the vast Sahara. Although these two great deserts are the two most productive areas, the Southern High Plains in USA (New Mexico and Texas) and Nullarbor Plain, Western Australia have great potential for meteorite recovery. The number of meteorite finds from Roosevelt County, New Mexico alone exceeds 100 in only approximately 11 km{sup 2} area. Most meteorites from this area have been found on the floors of active deflation basins (blowouts) that have been excavated from a mantle of sand dunes. This area has no apparent fluvial or permafrost activity within the last 50,000 years, suggesting that only prevailing winds and natural aridity aid in the concentration and preservation of meteorites. The authors investigated these deflation surfaces in Lea County (the SE corner of New Mexico) and neighboring Winkler County, Texas following a prior search in this area which found two chondrites. They found a tiny H4 chondrite in this search and here they report its mineralogy and petrology along with preliminary data on its exposure history

Surgical Treatment of Diabetic Foot Ulcers Complicated by Osteomyelitis with Gentamicin-Loaded Calcium Sulphate-Hydroxyapatite Biocomposite

Diabetic foot ulcers, complicated by osteomyelitis, can be treated by surgical resection, dead space filling with gentamicin-loaded calcium sulphate-hydroxyapatite (CaS-HA) biocomposite, and closure of soft tissues and skin. To assess the feasibility of this treatment regimen, we conducted a multicenter retrospective cohort study of patients after failed conventional treatments. From 13 hospitals we included 64 patients with forefoot (n = 41 (64%)), midfoot (n = 14 (22%)), or hindfoot (n = 9 (14%)) ulcers complicated by osteomyelitis. Median follow-up was 43 (interquartile range, 20-61) weeks. We observed wound healing in 54 patients (84%) and treatment success (wound healing without ulcer recurrence) in 42 patients (66%). Treatment failures (no wound healing or ulcer recurrence) led to minor amputations in four patients (6%) and major amputations in seven patients (11%). Factors associated with treatment failures in univariable Cox regression analysis were gentamicin-resistant osteomyelitis (hazard ratio (HR), 3.847; 95%-confidence interval (CI), 1.065-13.899), hindfoot ulcers (HR, 3.624; 95%-CI, 1.187-11.060) and surgical procedures with gentamicin-loaded CaS-HA biocomposite that involved minor amputations (HR, 3.965; 95%-CI, 1.608-9.777). In this study of patients with diabetic foot ulcers, complicated by osteomyelitis, surgical treatment with gentamicin-loaded CaS-HA biocomposite was feasible and successful in 66% of patients. A prospective trial of this treatment regimen, based on a uniform treatment protocol, is required

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication

Background: Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. Methods: The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. Results: When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population

The frequency of osteogenic activities and the pattern of intermittence between periods of physical activity and sedentary behaviour affects bone mineral content: the cross-sectional NHANES study

BACKGROUND: Sedentary behaviours, defined as non exercising seated activities, have been shown to have deleterious effects on health. It has been hypothesised that too much sitting time can have a detrimental effect on bone health in youth. The aim of this study is to test this hypothesis by exploring the association between objectively measured volume and patterns of time spent in sedentary behaviours, time spent in specific screen-based sedentary pursuits and bone mineral content (BMC) accrual in youth. METHODS: NHANES 2005–2006 cycle data includes BMC of the femoral and spinal region via dual-energy X-ray absorptiometry (DEXA), assessment of physical activity and sedentary behaviour patterns through accelerometry, self reported time spent in screen based pursuits (watching TV and using a computer), and frequency of vigorous playtime and strengthening activities. Multiple regression analysis, stratified by gender was performed on N = 671 males and N = 677 females aged from 8 to 22 years. RESULTS: Time spent in screen-based sedentary behaviours is negatively associated with femoral BMC (males and females) and spinal BMC (females only) after correction for time spent in moderate and vigorous activity. Regression coefficients indicate that an additional hour per day of screen-based sitting corresponds to a difference of −0.77 g femoral BMC in females [95% CI: -1.31 to −0.22] and of −0.45 g femoral BMC in males [95% CI: -0.83 to −0.06]. This association is attenuated when self-reported engagement in regular (average 5 times per week) strengthening exercise (for males) and vigorous playing (for both males and females) is taken into account. Total sitting time and non screen-based sitting do not appear to have a negative association with BMC, whereas screen based sedentary time does. Patterns of intermittence between periods of sitting and moderate to vigorous activity appears to be positively associated with bone health when activity is clustered in time and inter-spaced with long continuous bouts of sitting. CONCLUSIONS: Some specific sedentary pursuits (screen-based) are negatively associated with bone health in youth. This association is specific to gender and anatomical area. This relationship between screen-based time and bone health is independent of the total amount of physical activity measured objectively, but not independent of self-reported frequency of strengthening and vigorous play activities. The data clearly suggests that the frequency, rather than the volume, of osteogenic activities is important in counteracting the effect of sedentary behaviour on bone health. The pattern of intermittence between sedentary periods and activity also plays a role in bone accrual, with clustered short bouts of activity interspaced with long periods of sedentary behaviours appearing to be more beneficial than activities more evenly spread in time

Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation

Tumorimmunolog

The Golden Meteorite Fall: Fireball Trajectory, Orbit and Meteorite Characterization

The Golden (British Columbia, Canada) meteorite fall occurred on Oct 4, 2021 at 0534 UT with the first recovered fragment (1.3 kg) landing on an occupied bed. The meteorite is an unbrecciated, low-shock (S2) ordinary chondrite of intermediate composition, typed as an L/LL5. From noble gas measurements the cosmic ray exposure age is 25 Ma while gas retention ages are all >2 Ga. Short-lived radionuclides and noble gas measurements of the pre-atmospheric size overlap with estimates from infrasound and lightcurve modelling producing a preferred pre-atmospheric mass of 70-200 kg. The orbit of Golden has a high inclination (23.5 degs) and is consistent with delivery from the inner main belt. The highest probability (60%) of an origin is from the Hungaria group. We propose that Golden may originate among the background S-type asteroids found interspersed in the Hungaria region. The current collection of 18 L and LL chondrite orbits shows a strong preference for origins in the inner main belt, suggesting multiple parent bodies may be required to explain the diversity in CRE ages and shock states.Comment: 92 Pages, 20 Tables, 21 Figures, plus 3 appendices, accepted in Meteoritics and Planetary Science Oct 26 202

The Golden meteorite fall: Fireball trajectory, orbit, and meteorite characterization

The Golden (British Columbia, Canada) meteorite fall occurred on October 4, 2021 at 0534 UT with the first recovered fragment (1.3 kg) landing on an occupied bed. The associated fireball was recorded by numerous cameras permitting reconstruction of its trajectory and orbit. The fireball entered the atmosphere at a 54° angle from the horizontal at a speed of 18 km s−1. The fireball reached a peak brightness of −14, having first become luminous at a height of >84 km and ending at 18 km altitude. Analysis of the infrasonic record of the bolide produced an estimated mass of (Formula presented.) kg while modeling of the fireball light curve suggests an initial mass near 70 kg. The fireball experienced a major flare near 31 km altitude where more than half its mass was lost in the form of dust and gram-sized fragments under a dynamic pressure of 3.3 MPa. The strength and fragmentation behavior of the fireball were similar to those reported for other meteorite-producing fireballs (Borovička et al., 2020). Seven days after the fireball occurred, an additional 0.9 kg fragment was recovered during the second day of dedicated searching guided by initial trajectory and dark flight calculations. Additional searching in the fall and spring of 2021–2022 located no additional fragments. The meteorite is an unbrecciated, low-shock (S2) ordinary chondrite of intermediate composition, typed as an L/LL5 with a grain density of ~3530 k gm−3, an average bulk density of 3150 kg m−3 and calculated porosity of ~10%. From noble gas measurements, the cosmic ray exposure age is 25 ± 4 Ma while gas retention ages are all >2 Ga. Short-lived radionuclides and noble gas measurements of the pre-atmospheric size overlap with estimates from infrasound and light curve modeling producing a preferred pre-atmospheric mass of 70–200 kg. The orbit of Golden has a high inclination (23.5°) and is consistent with delivery from the inner main belt. The highest probability (60%) of an origin is from the Hungaria group. We propose that Golden may originate among the background S-type asteroids found interspersed in the Hungaria region. The current collection of 18 L/LL—chondrite orbits shows a strong preference for origins in the inner main belt, suggesting multiple parent bodies may be required to explain the diversity in CRE ages and shock states

Mineralogy and petrology of the Murrili meteorite

No abstract available