Effect of the COVID-19 Pandemic on Rates and Epidemiology of Clostridioides difficile Infection in One VA Hospital.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on the rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed both prior to the COVID-19 pandemic (2015 to 2019) and during the pandemic (2020-2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from October 2019 to March 2022. CDI case numbers declined by 43.2% in 2020 to 2021 compared to the annual mean over the previous 5 years. The stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; p = 0.013). Inpatient hospitalization rates declined, and rates of CDI among inpatients were reduced by 34.2% from 2020 to 2021. The mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89-3.87) vs. 1.92 (95% CI: 1.27-2.56); p = <0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic, from 8 March 2020, to 30 June 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%); After adjusting for CDI risk factors, a multivariable logistic regression model revealed that the odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03-39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic, but subsequently disappeared, and overall CDI rates declined.

Clinical trial facilitators: A novel approach to support the execution of clinical research at the study site level.

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.), Operation Warp Speed (OWS) was the program designated to coordinate such efforts. OWS was a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector, that aimed to help accelerate control of the COVID-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. The U.S. Department of Veterans Affairs' (VA) was identified as a potential collaborator in several large-scale OWS Phase III clinical trial efforts designed to evaluate the safety and efficacy of various vaccines that were in development. Given the global importance of these trials, it was recognized that there would be a need for a coordinated, centralized effort within VA to ensure that its medical centers (sites) would be ready and able to efficiently initiate, recruit, and enroll into these trials. The manuscript outlines the partnership and start-up activities led by two key divisions of the VA's Office of Research and Development's clinical research enterprise. These efforts focused on site and enterprise-level requirements for multiple trials, with one trial serving as the most prominently featured of these studies within the VA. As a result, several best practices arose that included designating clinical trial facilitators to study sites to support study initiation activities and successful study enrollment at these locations in an efficient and timely fashion.

Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD. METHODS AND ANALYSIS: Veterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period. ETHICS AND DISSEMINATION: This study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT03625648.

Randomized Controlled Trial of Physical Exercise in Diabetic Veterans With Length-Dependent Distal Symmetric Polyneuropathy.

Rationale: Physical exercise is an essential adjunct to the management of patients with type 2 diabetes mellitus. Therapeutic interventions that improve blood flow to peripheral nerves, such as exercise, may slow the progression of neuropathy in the diabetic patient. Aims: This randomized clinical trial was conducted to determine whether a structured program of aerobic, isokinetic strength, or the combination of aerobic-isokinetic strength exercise intervention alters peripheral nerve function in glycemic-controlled diabetic patients with advanced length-dependent distal symmetric polyneuropathy. Methods: Forty-five patients with type 2 diabetes mellitus exhibiting tight glycemic control (HbA1c intergroup range 7.2-8.0%) were randomized by block design across four experimental groups: sedentary controls (n = 12), aerobic exercise (n = 11), isokinetic strength (n = 11), or the combination of aerobic-isokinetic strength training (n = 11). Patients randomized to training groups exercised 3× per week for 12 weeks, whereas patients randomized to the sedentary control group received standard of care. To minimize attention and educational bias, all patients attended a 12-session health promotion educational series. At baseline, immediately following intervention, and again at 12-week post-intervention, detailed nerve conduction studies were conducted as a primary outcome measure. At these same intervals, all patients completed as secondary measures quantitative sensory testing, symptom-limited treadmill stress tests, and a Short-Form 36-Veterans Questionnaire (SF-36V). Results: Of the 45 patients randomized into this study, 37 (82%) had absent sural nerve responses, 19 (42%) had absent median sensory nerve responses, and 17 (38%) had absent ulnar sensory nerve responses. By comparison, responses from tibial nerves were absent in only three (7%) subjects while responses from peroneal nerves were absent in five (11%) subjects. Eleven (92%) of 12 patients that had volunteered to be biopsied exhibited abnormal levels of epidermal nerve fiber densities. Exercise, regardless of type, did not alter sensory or motor nerve electrodiagnostic findings among those patients exhibiting measurable responses (ANOVA). There was, however, a modest (p = 0.01) beneficial effect of exercise on sensory nerve function (Fisher's Exact Test). Importantly, the beneficial effect of exercise on sensory nerve function was enhanced (p = 0.03) during the post-intervention interval. In addition, three of six patients that had undergone exercise intervention exhibited a marked 1.9 ± 0.3-fold improvement in epidermal nerve fiber density. By comparison, none of three sedentary patients whom agreed to be biopsied a second time showed improvement in epidermal nerve fiber density. Compared to baseline values within groups, and compared with sedentary values across groups, neither aerobic, isokinetic strength, or the combination of aerobic-isokinetic strength exercise intervention altered peak oxygen uptake. Patients that underwent aerobic or the combined aerobic-isokinetic strength exercise intervention, however, demonstrated an increase in treadmill test duration that was sustained over the 12-week post-intervention period. Conclusion: A 12-week course of physical exercise, regardless of type, does not alter sensory or motor nerve electrodiagnostic findings. In a subset of patients, a short-term structured program of aerobic exercise may selectively improve sensory nerve fiber function. Large-scale exercise lifestyle intervention trials are warranted to further evaluate the impact of aerobic exercise on sensory nerve fiber function in diabetic neuropathic patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT00955201.

Structured Exercise in Obese Diabetic Patients with Chronic Kidney Disease: A Randomized Controlled Trial.

BACKGROUND: Patients with type 2 diabetes mellitus (DM), obesity, and chronic kidney disease (CKD) are generally physically inactive and may benefit from exercise. Our objective was to determine the effects of structured exercise on physical fitness, kidney function, endothelial function, inflammation, and body composition in such patients. METHODS: In this randomized, controlled trial, 36 male patients (age 49-81) were randomly assigned to exercise + diet management (n = 18) or diet alone (n = 18). Participants were eligible if they had type 2 DM, body mass index >30 kg/m2, CKD stages 2-4, and persistent proteinuria (>200 mg/g creatinine for >3 months). The exercise intervention was a 12-week (3 days per week) program of aerobic and resistance training followed by 40 weeks of home exercise. The primary outcome measure was change from baseline in urine protein to creatinine ratio (UPCR) at 12 and 52 weeks. RESULTS: Thirty-two participants completed the study (14 exercise + diet, 18 diet-alone group). The change from baseline in UPCR was slightly greater in the diet-alone group at 12 weeks but not at 52 weeks. Changes in both symptom-limited and constant-workrate treadmill times were significantly higher in the exercise + diet group at 12 weeks but not at 52 weeks. There were no significant differences in urine albumin to creatinine ratio, estimated glomerular filtration rate, endothelial function, inflammation, or body composition between the groups. CONCLUSIONS: In obese diabetic subjects with CKD, structured exercise improved exercise capacity but not body composition or renal function. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Validity and reliability of rectus femoris ultrasound measurements: Comparison of curved-array and linear-array transducers.

Muscle-mass loss augers increased morbidity and mortality in critically ill patients. Muscle-mass loss can be assessed by wide linear-array ultrasound transducers connected to cumbersome, expensive console units. Whether cheaper, hand-carried units equipped with curved-array transducers can be used as alternatives is unknown. Accordingly, our primary aim was to investigate in 15 nondisabled subjects the validity of measurements of rectus femoris cross-sectional area by using a curved-array transducer against a linear-array transducer-the reference-standard technique. In these subjects, we also determined the reliability of measurements obtained by a novice operator versus measurements obtained by an experienced operator. Lastly, the relationship between quadriceps strength and rectus area recorded by two experienced operators with a curved-array transducer was assessed in 17 patients with chronic obstructive pulmonary disease (COPD). In nondisabled subjects, the rectus cross-sectional area measured with the curved-array transducer by the novice and experienced operators was valid (intraclass correlation coefficient [ICC]: 0.98, typical percentage error [%TE]: 3.7%) and reliable (ICC: 0.79, %TE: 9.7%). In the subjects with COPD, both reliability (ICC: 0.99) and repeatability (%TE: 7.6% and 9.8%) were high. Rectus area was related to quadriceps strength in COPD for both experienced operators (coefficient of determination: 0.67 and 0.70). In conclusion, measurements of rectus femoris cross-sectional area recorded with a curved-array transducer connected to a hand-carried unit are valid, reliable, and reproducible, leading us to contend that this technique is suitable for cross-sectional and longitudinal studies.

Contrasting breathing retraining and helium-oxygen during pulmonary rehabilitation in COPD: a randomized clinical trial.

BACKGROUND: Breathing-retraining and helium-oxygen (heliox) have been used to improve exercise tolerance in COPD. We hypothesized that, in patients with COPD, exercise duration after exercise-training plus breathing-retraining and oxygen would be longer than after exercise-training plus heliox or after exercise-training plus oxygen alone. We also explored the short-term maintenance of gains in exercise duration after using each technique. METHODS: Of 192 COPD patients recruited, 103 were randomly assigned to exercise-training plus heliox (n = 33), exercise-training plus breathing-retraining and oxygen (n = 35) and exercise-training and oxygen (n = 35). FiO2 was 0.30 during testing and training in all groups. Patients exercised on a treadmill thrice-weekly for eight weeks. Before, at completion of training, and six-weeks later, patients underwent constant-load treadmill testing. RESULTS: At completion of training, improvements in exercise duration in the heliox and breathing-retraining groups were not significantly different. Compared to the exercise-training plus oxygen group, exercise duration improved more in the breathing-retraining group (P = 0.008) but not in the heliox group (P = 0.142). Hyperinflation was reduced with breathing-retraining plus oxygen compared to the other two groups. Six-weeks later, improvements in exercise duration were still greater with breathing-retraining than with exercise-training (P = 0.015). In contrast, improvements in exercise duration with heliox did not differ from those in the other two groups. CONCLUSIONS: In moderate-to-severe COPD, exercise-training combined with either heliox or with breathing-retraining yielded not significantly different improvements in exercise duration - with only the latter being superior to exercise-training. Six-weeks after training, these improvements were still greater after exercise-training plus breathing-retraining than after exercise-training. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00123422.

The effects of smoking status on walking ability and health-related quality of life in patients with peripheral arterial disease.

BACKGROUND: Smoking is a leading risk factor for peripheral arterial disease (PAD), yet little is known about the interrelationships among smoking status, walking endurance, calf muscle tissue oxygenation, and quality of life in patients with PAD. OBJECTIVE: The aim of this study was to explore the differences in factors associated with walking endurance including walk distance, perceived walking ability, measures of skeletal muscle tissue oxygenation (StO2), claudication pain, peak oxygen consumption per unit time, and quality of life in smokers versus nonsmokers. METHODS: A total of 105 patients with PAD performed progressive, symptom-limited treadmill test. Ankle-brachial index was measured at baseline. Calf muscle tissue oxygenation measures were obtained during testing. The RAND Short Form-36 and Walking Impairment Questionnaire were used to measure health-related quality of life (HR-QoL). RESULTS: In the total sample (36 current smokers, 69 nonsmokers), smokers had steeper declines in StO2 from baseline to 2 minutes (42.3% vs 33%, P = .05) and shorter distance walked to onset of claudication pain (142.6 vs 247.7 m) than did nonsmokers (P < .0125), despite having no differences in ankle-brachial index, peak oxygen consumption per unit time, or any momentary measure of StO2 during walking. Smokers reported significantly lower HR-QoL on the Short Form-36 in several domains but no differences in the Walking Impairment Questionnaire measures. The smokers were younger than the nonsmokers; however, when age was entered as a covariate in the analyses, the results remained unchanged. CONCLUSIONS: These findings suggest that smokers have lower HR-QoL than do nonsmokers with PAD and that smoking confers risks for disrupted tissue oxygenation above those seen in patients who do not smoke.

The Effects of Walking or Walking-with-Poles Training on Tissue Oxygenation in Patients with Peripheral Arterial Disease.

This randomized trial proposed to determine if there were differences in calf muscle StO(2) parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program. Data were collected on 85 patients who were randomized to a traditional walking program (n = 40) or walking-with-poles program (n = 45) of exercise training. Patients walked for 3 times weekly for 12 weeks. Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests (n = 36 traditional walking and n = 35 walking-with-poles). Using the near-infrared spectroscopy measures, StO(2) was measured prior to, during, and after exercise. At baseline, calf muscle oxygenation decreased from 56 ± 17% prior to the treadmill test to 16 ± 18% at peak exercise. The time elapsed prior to reaching nadir StO(2) values increased more in the traditional walking group when compared to the walking-with-poles group. Likewise, absolute walking time increased more in the traditional walking group than in the walking-with-poles group. Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program. In conclusion, the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD.

Comparison of walking with poles and traditional walking for peripheral arterial disease rehabilitation.

PURPOSE: The purpose of this study was to compare the effects of a 24-week walking with poles rehabilitation program with a traditional 24-week walking program on physical function in patients with peripheral arterial disease (PAD). METHODS: Patients with PAD (n = 103, age = 69.7 ± 8.9 years, ankle-brachial index < 0.90 or evidence of calcified vessels) were randomized into a rehabilitation program of traditional walking (n = 52) or walking with poles (n = 51). Patients exercised 3 times per week for 24 weeks. Exercise endurance was measured by time walked on a constant work rate treadmill test at 6, 12, and 24 weeks. Perceived physical function was measured by the Medical Outcomes Study Short Form-36 and Walking Impairment Questionnaire. Tissue oxygenation was measured using near-infrared spectroscopy. RESULTS: Patients assigned to the traditional walking group walked longer at 24 weeks than those assigned to the pole walking group (21.10 ± 17.07 minutes and 15.02 ± 12.32 minutes, respectively, P = .037). There were no differences between the groups in tissue oxygenation. However, there was a significant lengthening of time for which it took to reach minimum tissue oxygenation values (P < .001) within the groups on the constant work rate test. There were no differences between the groups in perceived physical function as measured by the Physical Function subscale on the Medical Outcomes Study Short Form-36 or perceived walking distance as measured by the Walking Distance subscale on the Walking Impairment Scale. CONCLUSIONS: Traditional walking was superior to walking with poles in increasing walking endurance on a constant work rate treadmill test for patients with PAD.