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Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.
Vetrovsky, T, Siranec, M, Frybova, T, Gant, I, Svobodova, I, Linhart, A, Parenica, J, Miklikova, M, Sujakova, L, Pospisil, D, et al
Circulation. 2024;(3):177-188
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BACKGROUND Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.
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Late postoperative vitreous cavity hemorrhage after vitrectomy for proliferative diabetic retinopathy-observation versus intervention.
Brar, AS, Behera, UC, Karande, S, Kanakagiri, A, Sugumar, S, Rani, PK, Vignesh, TP, Manayath, G, Salian, R, Giridhar, A, et al
Indian journal of ophthalmology. 2024;(Suppl 1):S22-S26
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Abstract
PURPOSE To analyze the outcome of intervention versus observation for vitreous cavity hemorrhage occurring after a 2-month period of blood-free cavity (late postoperative vitreous cavity hemorrhage-POVCH) in eyes operated by vitrectomy for complications of proliferative diabetic retinopathy (PDR). METHODS This study was a 10-year retrospective, observational, multi-center study involving eight major vitreoretinal surgical centers across India from January 2010 to December 2019. The primary objective of the study was to assess the visual and clinical outcomes of various management approaches for late POVCH. The key secondary objective was to determine the best management option that prevented recurrence. Patients with follow-up of less than 6 months of POVCH management were excluded. RESULTS The occurrence of late POVCH was studied in 261 eyes. The median time to occurrence was 7 months (range: 2-87) postvitrectomy/silicone oil removal. The majority (58%) experienced a single, nonrecurring POVCH event. Visual acuity outcome was independent of all management approaches (P = 0.179; mean follow-up 20.7 ± 14.1 months). With watchful observation, spontaneous resolution was noted in 83% (60/72 eyes) of eyes in 81.5 days (interquartile range, 169.75). Silicone oil injection was most effective in preventing recurrence (P < 0.001). CONCLUSION The current treatment practice of late POVCH management in PDR suggests that watchful observation for at least 3 months could be as efficacious as any surgical intervention.
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Survival and Long-Term Functional Status of COVID-19 Patients Requiring Prolonged Extracorporeal Membrane Oxygenation Support.
Martínez-Martínez, M, Schmidt, M, Broman, LM, Roncon-Albuquerque, R, Langouet, E, Campos, I, Argudo, E, Domènech Vila, JM, Sastre, SM, Gallart, E, et al
Annals of the American Thoracic Society. 2024;(3):449-455
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Rationale: Severe cases of acute respiratory distress syndrome (ARDS) may require prolonged (>28 d) extracorporeal membrane oxygenation (ECMO). In nonresolving disease, recovery is uncertain, and lung transplant may be proposed. Objectives: This study aims to identify the variables influencing survival and to describe the functional status of these patients at 6 months. Methods: This was a retrospective, multicenter, observational cohort study including patients requiring ECMO support for coronavirus disease (COVID-19)-related ARDS for >28 days. Multivariate analysis was performed using Cox regression in preselected variables and in least absolute shrinkage and selection operator selected variables. In a post hoc analysis to account for confounders and differences in awake strategy use by centers, treatment effects of the awake strategy were estimated using an augmented inverse probability weighting estimator with robust standard errors clustered by center. Results: Between March 15, 2020 and March 15, 2021, 120 patients required ECMO for >28 days. Sixty-four patients (53.3%) survived decannulation, 62 (51.7%) were alive at hospital discharge, and 61 (50.8%) were alive at 6-month follow-up. In the multivariate analysis, age (1.09; 95% confidence interval [CI], 1.03-1.15; P = 0.002) and an awake ECMO strategy (defined as the patient being awake, cooperative, and performing rehabilitation and physiotherapy with or without invasive mechanical ventilation at any time during the extracorporeal support) (0.14; 95% CI, 0.03-0.47; P = 0.003) were found to be predictors of hospital survival. At 6 months, 51 (42.5%) patients were at home, 42 (84.3%) of them without oxygen therapy. A cutoff point of 47 ECMO days had a 100% (95% CI, 76.8-100%) sensitivity and 60% (95% CI, 44.3-73.6%) specificity for oxygen therapy at 6 months, with 100% specificity being found in 97 days. Conclusions: Patients with COVID-19 who require ECMO for >28 days can survive with nonlimiting lung impairment. Age and an awake ECMO strategy may be associated with survival. Longer duration of support correlates with need for oxygen therapy at 6 months.
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Breath metabolomics for diagnosis of acute respiratory distress syndrome.
Zhang, S, Hagens, LA, Heijnen, NFL, Smit, MR, Brinkman, P, Fenn, D, van der Poll, T, Schultz, MJ, Bergmans, DCJJ, Schnabel, RM, et al
Critical care (London, England). 2024;(1):96
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.
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Implementation of Best Practices in Pancreatic Cancer Care in the Netherlands: A Stepped-Wedge Randomized Clinical Trial.
Mackay, TM, Latenstein, AEJ, Augustinus, S, van der Geest, LG, Bogte, A, Bonsing, BA, Cirkel, GA, Hol, L, Busch, OR, den Dulk, M, et al
JAMA surgery. 2024;(4):429-437
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IMPORTANCE Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. OBJECTIVE To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. DESIGN, SETTING, AND PARTICIPANTS This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). INTERVENTION The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. MAIN OUTCOMES AND MEASURES The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). RESULTS Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, -1.09, 95% CI, -3.05 to 0.94). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03513705.
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Efficacy and Safety of Calcifediol in Young Adults with Vitamin D Deficiency: A Phase I, Multicentre, Clinical Trial-POSCAL Study.
Guerra López, P, Urroz Elizalde, M, Vega-Gil, N, Sánchez Santiago, B, Zorrilla Martínez, I, Jiménez-Mercado, M, Jódar, E, Landeta Manzano, A, Campo Hoyos, C, Frías Iniesta, J
Nutrients. 2024;(2)
Abstract
Vitamin D deficiency is highly prevalent, and recent evidence suggests a possible association between vitamin D deficiency and various health conditions. The aim of this study was to assess monthly calcifediol treatments for vitamin D deficiency (or biweekly, if the deficiency was severe) in a young adult population with no associated comorbidities. This multicentre phase I trial started with a four month open-label treatment phase (TP) that included 101 participants (65% women with mean age 29.8 years). Eighty-two percent of the subjects (79/96) achieved 25(OH)D levels within the target range (20-60 ng/mL) by the end of the TP, and they were subsequently randomised and subjected to a double-blind, placebo-controlled, five month follow-up phase (FP). At the end of the FP, 89% of participants maintained vitamin D levels of >20 ng/mL with calcifediol, versus 49% with placebo (p < 0.001). Subjects receiving monthly calcifediol during both phases (n = 32) maintained 25(OH)D levels >20 ng/mL, whereas those on the placebo during the FP (n = 38) exhibited deficiency levels of 25(OH)D by the end of the study. No clinically relevant changes in bone metabolism parameters or toxic 25(OH)D levels were observed, and no serious adverse events were reported throughout the study. Calcifediol is a safe and effective treatment for vitamin D deficiency in the young adult population, but long-term use may be required to sustain optimal 25(OH)D levels.
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Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.
Shang, YX, Wei, SF, Yang, KP, Liu, Y, Wei, S, Dong, X, Wang, XC, Xie, ZM, Fang, RL, Liang, LN, et al
BMC complementary medicine and therapies. 2024;(1):21
Abstract
BACKGROUND This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION ISRCTN34355813. Registered on 25/01/2021.
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A Phase II Study of FOLFIRI Plus Ziv-Aflibercept After Trifluridine/Tipiracil Plus Bevacizumab in Patients with Metastatic Colorectal Cancer: WJOG 11018G.
Matsumoto, T, Yamamoto, Y, Kotaka, M, Masuishi, T, Tsuji, Y, Shoji, H, Hirata, K, Tsuduki, T, Makiyama, A, Izawa, N, et al
Targeted oncology. 2024;(2):181-190
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BACKGROUND Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients. OBJECTIVE We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses. METHODS This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex® multiplex assay U-kit. RESULTS Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month-not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1). CONCLUSIONS This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment. CLINICAL TRIAL REGISTRATION jRCTs041190100.
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Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial.
Gaengler, S, Sadlon, A, De Godoi Rezende Costa Molino, C, Willett, WC, Manson, JE, Vellas, B, Steinhagen-Thiessen, E, Von Eckardstein, A, Ruschitzka, F, Rizzoli, R, et al
The journal of nutrition, health & aging. 2024;(2):100037
Abstract
BACKGROUND The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D3, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE). METHODS The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years. RESULTS Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control. CONCLUSION Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D3, and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER NCT01745263.
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Adherence and impact of an oral nutritional supplement enriched in leucine, EVOO, EPA and DHA, and beta-glucans on the coverage of energy and protein requirements in patients with cancer and malnutrition: Alisenoc study.
Milla, SP, Luna, PPG, Casariego, AV, González, FV, Folgueras, TM, Jáuregui, OI, Rey, SG, Fernández, AC, Plaza, BL, Quintana, TC, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2024;:112355
Abstract
OBJECTIVE The aim of this study was to evaluate the impact of an enhanced ONS (enriched in EPA, DHA, leucine, and beta-glucans) on the dietary intake of cancer patients. METHODS A randomized, double-blind, parallel, controlled, and multicenter clinical trial was conducted in patients with cancer and malnutrition. The trial compared prescribed dietary advice and two packs per day, for 8 weeks, of a hypercaloric (400 kcal/pack) and hyperproteic ONS (20 g/pack) with fiber and specific ingredients (leucine, EPA and DHA, and beta-glucans) (enhanced-ONS) versus an isocaloric and isoproteic formula (standard-ONS) without specific ingredients. Food intake was assessed with a 3-day dietary survey, and adherence to the supplement with a patient self-completed diary. RESULTS Thirty-seven patients completed the intervention period. The combined intervention of dietary advice and ONS managed to increase the energy intake of the overall cohort by 792.55 (378.57) kcal/day, protein by 40.72 (19.56) g/day. Increases in energy and nutrient intakes were observed in both groups, both in dietary intake and associated exclusively with the supplement. The group that received the enhanced-ONS ingested a greater volume of product when there was a greater severity of malnutrition; a tumor location in the head, neck, upper digestive area, liver, or pancreas; more advanced stages of the tumor; or the receipt of more than one antineoplastic treatment. CONCLUSION The use of an enhanced-ONS helps meet the nutritional requirements of cancer patients, especially those who have a more compromised clinical condition, with high adherence, good tolerance, and acceptance.