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Importance: Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities.Objective: To determine whether telmisartan improves 6-minute walk distance, compared with placebo, in patients with lower extremity PAD at 6-month follow-up.Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 2 US sites and involving 114 participants. Enrollment occurred between December 28, 2015, and November 9, 2021. Final follow-up occurred on May 6, 2022.Interventions: The trial randomized patients using a 2 × 2 factorial design to compare the effects of telmisartan plus supervised exercise vs telmisartan alone and supervised exercise alone and to compare telmisartan alone vs placebo. Participants with PAD were randomized to 1 of 4 groups: telmisartan plus exercise (n = 30), telmisartan plus attention control (n = 29), placebo plus exercise (n = 28), or placebo plus attention control (n = 27) for 6 months. The originally planned sample size was 240 participants. Due to slower than anticipated enrollment, the primary comparison was changed to the 2 combined telmisartan groups vs the 2 combined placebo groups and the target sample size was changed to 112 participants.Main Outcomes and Measures: The primary outcome was the 6-month change in 6-minute walk distance (minimum clinically important difference, 8-20 m). The secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and the 36-Item Short-Form Health Survey physical functioning score. The results were adjusted for study site, baseline 6-minute walk distance, randomization to exercise vs attention control, sex, and history of heart failure at baseline.Results: Of the 114 randomized patients (mean age, 67.3 [SD, 9.9] years; 46 were women [40.4%]; and 81 were Black individuals [71.1%]), 105 (92%) completed 6-month follow-up. At 6-month follow-up, telmisartan did not significantly improve 6-minute walk distance (from a mean of 341.6 m to 343.0 m; within-group change: 1.32 m) compared with placebo (from a mean of 352.3 m to 364.8 m; within-group change: 12.5 m) and the adjusted between-group difference was -16.8 m (95% CI, -35.9 m to 2.2 m; P = .08). Compared with placebo, telmisartan did not significantly improve any of the 5 secondary outcomes. The most common serious adverse event was hospitalization for PAD (ie, lower extremity revascularization, amputation, or gangrene). Three participants (5.1%) in the telmisartan group and 2 participants (3.6%) in the placebo group were hospitalized for PAD.Conclusions and Relevance: Among patients with PAD, telmisartan did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support telmisartan for improving walking performance in patients with PAD.Trial Registration: ClinicalTrials.gov Identifier: NCT02593110. [ABSTRACT FROM AUTHOR]

Importance: Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor.Objective: To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control.Design, Setting, and Participants: Multicenter randomized clinical trial conducted at 4 US centers and including 305 participants. Enrollment occurred between September 25, 2015, and December 11, 2019; final follow-up was October 7, 2020.Interventions: Participants with PAD were randomized to low-intensity walking exercise (n = 116), high-intensity walking exercise (n = 124), or nonexercise control (n = 65) for 12 months. Both exercise groups were asked to walk for exercise in an unsupervised setting 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. The low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. Accelerometer data were viewable to a coach who telephoned participants weekly for 12 months and helped them adhere to their prescribed exercise. The nonexercise control group received weekly educational telephone calls for 12 months.Main Outcomes and Measures: The primary outcome was mean change in 6-minute walk distance at 12 months (minimum clinically important difference, 8-20 m).Results: Among 305 randomized patients (mean age, 69.3 [SD, 9.5] years, 146 [47.9%] women, 181 [59.3%] Black patients), 250 (82%) completed 12-month follow-up. The 6-minute walk distance changed from 332.1 m at baseline to 327.5 m at 12-month follow-up in the low-intensity exercise group (within-group mean change, -6.4 m [95% CI, -21.5 to 8.8 m]; P = .34) and from 338.1 m to 371.2 m in the high-intensity exercise group (within-group mean change, 34.5 m [95% CI, 20.1 to 48.9 m]; P < .001) and the mean change for the between-group comparison was -40.9 m (97.5% CI, -61.7 to -20.0 m; P < .001). The 6-minute walk distance changed from 328.1 m at baseline to 317.5 m at 12-month follow-up in the nonexercise control group (within-group mean change, -15.1 m [95% CI, -35.8 to 5.7 m]; P = .10), which was not significantly different from the change in the low-intensity exercise group (between-group mean change, 8.7 m [97.5% CI, -17.0 to 34.4 m]; P = .44). Of 184 serious adverse events, the event rate per participant was 0.64 in the low-intensity group, 0.65 in the high-intensity group, and 0.46 in the nonexercise control group. One serious adverse event in each exercise group was related to study participation.Conclusions and Relevance: Among patients with PAD, low-intensity home-based exercise was significantly less effective than high-intensity home-based exercise and was not significantly different from the nonexercise control for improving 6-minute walk distance. These results do not support the use of low-intensity home-based walking exercise for improving objectively measured walking performance in patients with PAD.Trial Registration: ClinicalTrials.gov Identifier: NCT02538900. [ABSTRACT FROM AUTHOR]

Importance: Clinical practice guidelines support home-based exercise for patients with peripheral artery disease (PAD), but no randomized trials have tested whether an exercise intervention without periodic medical center visits improves walking performance.Objective: To determine whether a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching improves walking ability over 9 months in patients with PAD.Design, Setting, and Participants: Randomized clinical trial conducted at 3 US medical centers. Patients with PAD were randomized between June 18, 2015, and April 4, 2017, to home-based exercise vs usual care for 9 months. Final follow-up was on December 5, 2017.Interventions: The exercise intervention group (n = 99) received 4 weekly medical center visits during the first month followed by 8 months of a wearable activity monitor and telephone coaching. The usual care group (n = 101) received no onsite sessions, active exercise, or coaching intervention.Main Outcomes and Measures: The primary outcome was change in 6-minute walk distance at 9-month follow-up (minimal clinically important difference [MCID], 20 m). Secondary outcomes included 9-month change in subcomponents of the Walking Impairment Questionnaire (WIQ) (0-100 score; 100, best), SF-36 physical functioning score, Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire (higher = better; MCID, 2 points), PROMIS satisfaction with social roles questionnaire, PROMIS pain interference questionnaire (lower = better; MCID range, 3.5-4.5 points), and objectively measured physical activity.Results: Among 200 randomized participants (mean [SD] age, 70.2 [10.4] years; 105 [52.5%] women), 182 (91%) completed 9-month follow-up. The mean change from baseline to 9-month follow-up in the 6-minute walk distance was 5.5 m in the intervention group vs 14.4 m in the usual care group (difference, -8.9 m; 95% CI, -26.0 to 8.2 m; P = .31). The exercise intervention worsened the PROMIS pain interference score, mean change from baseline to 9 months was 0.7 in the intervention group vs -2.8 in the usual care group (difference, 3.5; 95% CI, 1.3 to 5.8; P = .002). There were no significant between-group differences in the WIQ score, the SF-36 physical functioning score, or the PROMIS mobility or satisfaction with social roles scores.Conclusions and Relevance: Among patients with PAD, a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching, compared with usual care, did not improve walking performance at 9-month follow-up. These results do not support home-based exercise interventions of wearable devices and telephone counseling without periodic onsite visits to improve walking performance in patients with PAD.Trial Registration: clinicaltrials.gov Identifier: NCT02462824. [ABSTRACT FROM AUTHOR]

Importance: Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle.Objectives: To determine whether GM-CSF combined with supervised treadmill exercise improves 6-minute walk distance, compared with exercise alone and compared with GM-CSF alone; to determine whether GM-CSF alone improves 6-minute walk more than placebo and whether exercise improves 6-minute walk more than an attention control intervention.Design, Setting, and Participants: Randomized clinical trial with 2 × 2 factorial design. Participants were identified from the Chicago metropolitan area and randomized between January 6, 2012, and December 22, 2016, to 1 of 4 groups: supervised exercise + GM-CSF (exercise + GM-CSF) (n = 53), supervised exercise + placebo (exercise alone) (n = 53), attention control  + GM-CSF (GM-CSF alone) (n = 53), attention control + placebo (n = 51). The final follow-up visit was on August 15, 2017.Interventions: Supervised exercise consisted of treadmill exercise 3 times weekly for 6 months. The attention control consisted of weekly educational lectures by clinicians for 6 months. GM-CSF (250 μg/m2/d) or placebo were administered subcutaneously (double-blinded) 3 times/wk for the first 2 weeks of the intervention.Main Outcomes and Measures: The primary outcome was change in 6-minute walk distance at 12-week follow-up (minimum clinically important difference, 20 m). P values were adjusted based on the Hochberg step-up method.Results: Of 827 persons evaluated, 210 participants with PAD were randomized (mean age, 67.0 [SD, 8.6] years; 141 [67%] black, 82 [39%] women). One hundred ninety-five (93%) completed 12-week follow-up. At 12-week follow-up, exercise + GM-CSF did not significantly improve 6-minute walk distance more than exercise alone (mean difference, -6.3 m [95% CI, -30.2 to +17.6]; P = .61) or more than GM-CSF alone (mean difference, +28.7 m [95% CI, +5.1 to +52.3]; Hochberg-adjusted P = .052). GM-CSF alone did not improve 6-minute walk more than attention control + placebo (mean difference, -1.4 m [95% CI, -25.2 to +22.4]; P = .91). Exercise alone improved 6-minute walk compared with attention control + placebo (mean difference, +33.6 m [95% CI, +9.4 to +57.7]; Hochberg-adjusted P = .02).Conclusions and Relevance: Among patients with PAD, supervised treadmill exercise significantly improved 6-minute walk distance compared with attention control + placebo, whereas GM-CSF did not significantly improve walking performance, either when used alone or when combined with supervised treadmill exercise. These results confirm the benefits of exercise but do not support using GM-CSF to treat walking impairment in patients with PAD.Trial Registration: clinicaltrials.gov Identifier: NCT01408901. [ABSTRACT FROM AUTHOR]

Importance: Clinical practice guidelines state there is insufficient evidence to support advising patients with peripheral artery disease (PAD) to participate in a home-based walking exercise program.Objective: To determine whether a home-based walking exercise program that uses a group-mediated cognitive behavioral intervention, incorporating both group support and self-regulatory skills, can improve functional performance compared with a health education control group in patients with PAD with and without intermittent claudication.Design, Setting, and Patients: Randomized controlled clinical trial of 194 patients with PAD, including 72.2% without classic symptoms of intermittent claudication, performed in Chicago, Illinois between July 22, 2008, and December 14, 2012.Interventions: Participants were randomized to 1 of 2 parallel groups: a home-based group-mediated cognitive behavioral walking intervention or an attention control condition.Main Outcomes and Measures: The primary outcome was 6-month change in 6-minute walk performance. Secondary outcomes included 6-month change in treadmill walking, physical activity, the Walking Impairment Questionnaire (WIQ), and Physical and Mental Health Composite Scores from the 12-item Short-Form Health Survey.Results: Participants randomized to the intervention group significantly increased their 6-minute walk distance ([reported in meters] 357.4 to 399.8 vs 353.3 to 342.2 for those in the control group; mean difference, 53.5 [95% CI, 33.2 to 73.8]; P < .001), maximal treadmill walking time (intervention, 7.91 to 9.44 minutes vs control, 7.56 to 8.09; mean difference, 1.01 minutes [95% CI, 0.07 to 1.95]; P = .04), accelerometer-measured physical activity over 7 days (intervention, 778.0 to 866.1 vs control, 671.6 to 645.0; mean difference, 114.7 activity units [95% CI, 12.82 to 216.5]; P = .03), WIQ distance score (intervention, 35.3 to 47.4 vs control, 33.3 to 34.4; mean difference, 11.1 [95% CI, 3.9 to 18.1]; P = .003), and WIQ speed score (intervention, 36.1 to 47.7 vs control, 35.3-36.6; mean difference, 10.4 [95% CI, 3.4 to 17.4]; P = .004).Conclusion and Relevance: A home-based walking exercise program significantly improved walking endurance, physical activity, and patient-perceived walking endurance and speed in PAD participants with and without classic claudication symptoms. These findings have implications for the large number of patients with PAD who are unable or unwilling to participate in supervised exercise programs.Trial Registration: clinicaltrials.gov Identifier: NCT00693940. [ABSTRACT FROM AUTHOR]

The article presents the findings of a research conducted on examining the influence of common variation within genes encoding vitamin D-binding protein, megalin, and cubilin and vitamin D receptor (VDR) in 25-hydroxyvitamin D concentrations in low 25-hydroxyvitamin D with major clinical outcomes. It discusses the methodology of the research which includes the examination of single-nucleotide polymorphisms. The research concludes that familiar associations of 25-hydroxyvitamin D with clinical outcomes vary, due to genetic differences in the vitamin D receptor.

The article discusses a study of the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with ST-segment elevation myocardial infarction (STEMI) in the U.S. conducted from October 2006 to February 2010. The risk for developing infarct expansion and left ventricular (LV) remodeling are facing patients who survive STEMI. Vital signs, hemoglobin level, reticulocyte count and clinical events were some of the factors considered as safety end points. Results show a lack of association between infarct size and time from study drug administration to first cardiac magnetic resonance (CMR). Also noted is the higher incidence of adverse events in participants who received epoetin alfa.

The article discusses a study which evaluated the relationship between gait speed and survival in geriatric patients, as well as determined the degree to which gait speed explains variability in survival after accounting for age and sex. The study's design, setting and participants are described. Main outcome measures include survival rates and life expectancy. The study found that survival increased across the full range of gait speeds based on the pooled analysis of individual data from 9 selected cohorts.

The article presents a randomized controlled trial which examined whether supervised treadmill exercise or lower extremity resistance training improved the functional performance of patients with peripheral arterial disease with and without classic intermittent claudication symptoms. The primary outcome was six-minute walk performance and the short physical performance battery. 6-minute walk performance, brachial artery flow-mediated dilation, treadmill walking performance, and quality of life were improved with supervised treadmill training. The short physical performance battery scores were not improved. Lower extremity resistance training improved functional performance.

This article reports on a study to see if poor nutrition is a cause for the physical and mental decline in the elderly. As the population in the U.S. ages, it become more important to keep the elderly healthy longer to save medical dollars. The study sought to see if low serum concentration of micronutrients were associated with a decline in physical function among elderly people living in the community. The study found that a low serum concentration of vitamin E is associated with a decline in physical function in the elderly. The authors say clinical trials should be conducted to see if there is an optimal concentration of vitamin E that would slow down the disabilities of aging.

Context: Among individuals with lower-extremity peripheral arterial disease (PAD), specific leg symptoms and the ankle brachial index (ABI) are cross-sectionally related to the degree of functional impairment. However, relations between these clinical characteristics and objectively measured functional decline are unknown.Objective: To define whether PAD, ABI, and specific leg symptoms predict functional decline at 2-year follow-up.Design, Setting, and Participants: Prospective cohort study among 676 consecutively identified individuals (aged > or =55 years) with and without PAD (n = 417 and n = 259, respectively), with baseline functional assessments occurring between October 1, 1998, and January 31, 2000, and follow-up assessments scheduled 1 and 2 years thereafter. PAD was defined as ABI less than 0.90, and participants with PAD were categorized at baseline into 1 of 5 mutually exclusive symptom groups.Main Outcome Measures: Mean annual changes in 6-minute walk performance and in usual-paced and fast-paced 4-m walking velocity, adjusted for age, sex, race, prior-year functioning, comorbid diseases, body mass index, pack-years of cigarette smoking, and patterns of missing data.Results: Lower baseline ABI values were associated with greater mean (95% confidence interval) annual decline in 6-minute walk performance (-73.0 [-142 to -4.2] ft for ABI <0.50 vs -58.8 [-83.5 to -34.0] ft for ABI 0.50 to <0.90 vs -12.6 [-40.3 to 15.1] ft for ABI 0.90-1.50, P =.02). Compared with participants without PAD, PAD participants with leg pain on exertion and rest at baseline had greater mean annual decline in 6-minute walk performance (-111 [-173 to -50.0] ft vs -8.67 [-36.9 to 19.5] ft, P =.004), usual-pace 4-meter walking velocity (-0.06 [-0.09 to -0.02] m/sec vs -0.01 (-0.03 to 0.003] m/sec, P =.02), and fastest-pace 4-meter walking velocity (-0.07 [-0.11 to -0.03] m/sec vs -0.02 [-0.04 to -0.006] m/sec, P =.046). Compared with participants without PAD, asymptomatic PAD was associated with greater mean annual decline in 6-minute walk performance (-76.8 (-135 to -18.6] ft vs -8.67 (-36.9 to 19.5] ft, P =.04) and an increased odds ratio for becoming unable to walk for 6 minutes continuously (3.63; 95% confidence interval, 1.58-8.36; P =.002).Conclusions: Baseline ABI and the nature of leg symptoms predict the degree of functional decline at 2-year follow-up. Previously reported lack of worsening in claudication symptoms over time in patients with PAD may be more related to declining functional performance to than lack of disease progression. [ABSTRACT FROM AUTHOR]

Presents letters to the editor. Response to an article about the use of antidepressant medication for chronic tension headaches; Who should be screened for osteoporosis; Discussion of studies regarding violence in children's films and video games; Others.

Presents a study, the objective of which is to characterize hospital diagnoses, procedures and charges, and nursing home admissions in the year when older persons become severely disabled. Comparison to those in whom severe disability develops rapidly with those in whom disability develops gradually; Design; Setting; Subjects; Main outcome measures; Results; Conclusions.

Discusses a study which determines whether depressive symptoms in older persons increase the risk of subsequent decline in physical function. Measured by objective performance-based tests; Design; Setting; Participants; Main outcome measures; Results; Conclusions.

The article presents a reply to a letter to the editor discussing the article "Serum micronutrient concentrations and decline in physical function among older persons," by B. Bartali, EA Frongillo, JM Guralnik, et al published in a previous issue.