Significant Difference In Change Research Articles

Safety and Efficacy of Levomilnacipran Extended Release in Pediatric Patients Aged 7-17 Years with Major Depressive Disorder: Results of Two Phase 3, Randomized, Double-Blind Studies.

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

The relationship between levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in the serum of elderly and acute myocardial infarction.

This study aimed to explore the relationship between the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hypersensitive C-reactive protein (hs-CRP) and the prognosis of acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI) treatment. A total of 118 early-onset AMI patients who successfully received PCI (in the PCI group, blood samples were collected before PCI, 12, 24, 48 h after PCI, and 90 d follow-up period) and 52 AMI patients who received only cardioangiography (CAG) (in the CAG group, blood samples were collected before CAG, 12, 24, 48 h after CAG, and 90 d follow-up period). The serum levels of IL-6, hs-CRP and TNF-α were detected, and the incidence of major adverse cardiac events (MACE) in the PCI group during follow-up was observed. The basic levels of IL-6, hs-CRP, and TNF-α between the PCI group and the CAG group were not statistically different (P>0.05); there was no statistically significant difference in changes of serum IL-6, hs-CRP, and TNF-α in the CAG group before and after CAG (P>0.05); IL-6, hs-CRP, and TNF-α in the PCI group were significantly higher than those before treatment (P<0.01); in the PCI group, the levels of IL-6, hs-CRP and TNF-α between the MACE group and the MACE-free group were statistically different (P<0.05). Serum IL-6, hs-CRP and TNF-α levels in AMI patients after PCI significantly increased in the short term, and PCI may induce an inflammatory response; the high levels of inflammatory cytokines, IL-6, hs-CRP, and TNF-α, in peripheral blood may have an important reference value for MACE and short-term prognosis in early-onset AMI patients after PCI.

Effect Of Triamcinolone Trigger Point Injection On Changes In TNF-α Levels And Oswestry Disability Index (ODI) Scores Non-Specific Low Back Pain (LBP) Patients

Background: Low back pain (LBP) is the most common musculoskeletal problem and a major cause of worldwide disability causing increased health costs and indirect costs associated with reduced or lost productivity. One of the therapeutic management of LBP is Triamcinolone trigger point injection. Until now, research on the effect of Triamcinolone trigger point injection on changes in TNF-α levels and Oswestry Disability Index (ODI) scores in Non-Specific LBP patients is still limited. Objective: To analyze the effect of Triamcinolone trigger point injection on changes in TNF-α levels and ODI scores before and after Triamcinolone trigger point injection in Non-Specific LBP patients. Methods: This is a quasi-experimental analytic observational study with a pre and post-test group design approach. Subjects were diagnosed with Non-Specific LBP who had met the inclusion criteria (acute pain less than 3 months, patient age 30-55 years, moderate-severe pain intensity, had never received a Triamcinolone trigger point injection) with the exclusion criteria patients experiencing severe pain. not only caused by NPB. The study subjects were checked for TNF-α levels and ODI scores before and after the Triamcinolone trigger point injection. Then a paired T-test was carried out. Results: During the study period September - November 2022 at the Neurology Outpatient Polyclinic, RSUP Dr. Kariadi Semarang obtained 32 subjects. There was a significant difference between changes in TNF-α levels before and after Triamcinolone trigger point injection (p=0.000). There was a significant difference in ODI scores before and after the Triamcinolone trigger point injection (p=0.000). There was no significant relationship between the risk factors for gender, occupation, BMI, physiotherapy, and changes in TNF-α levels with changes in the ODI score. Conclusion: There is a significant difference in changes in TNF-α levels and ODI scores before and after Triamcinolone trigger point injection.

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA.

We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0mg/dL and < 5.0mg/dL) or the standard therapy group (serum UA level ≥ 6.0mg/dL and < 7.0mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23mg/dL at baseline and 6.13mg/dL at 52weeks. In the Intensive therapy group, mean serum UA was 8.15mg/dL at baseline and 5.25mg/dL at 52weeks. There was no significant difference in changes in log ACR at 52weeks between the Intensive therapy and the Standard therapy groups. This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146).

Effect of Storage Period on Platelet Count and Erythrocyte Morphology in Whole Blood Bags

Platelets and erythrocytes undergo transformation during storage, which may cause them to become inactive or non-functional. In transfusion medicine, the storage period of platelets and erythrocytes is very important because they change shape during storage, such as during echinocytosis, spherocytosis, and crenation. This study aims to determine the effect of storage period on platelet count and erythrocyte morphology in whole blood samples. Methods: This study used simple random sampling method to determine the effect of time on the occurrence of a disease. The study was conducted from January to April 2022 at the Semarang Regency Blood Donor Unit. This study focuses on the effect of time on the occurrence of a disease in whole blood samples. This study used automated sampling with hematology analyzer to analyze the data. Data collection was done with informed consent from donors and laboratory data from Blood Donor Unit Semarang Regency. The results showed a significant difference in changes in platelet count and erythrocyte morphology between day 0 and day 30 storage periods, with a p value of 0.014. Conclusions. There is a significant difference in changes in platelet count and erythrocyte morphology between day 0 and day 30 storage periods with a p value of 0.014. It is recommended that in the process of storing blood bags in the Blood Donor Unit, excessive shelf life is avoided to maintain blood quality.

Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption.

Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD). We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (n = 93), MASLD plus increased alcohol intake (MetALD; n = 23) and ALD (n = 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, n = 75) was also evaluated. In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 (P < 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups. Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).

Analysis of the Mechanical Degradability of Biodegradable Polymer-Based Bags in Different Environments

Biodegradable polymer-based bags were developed as an alternative to plastic. However, their degradation in environmental conditions has not been fully investigated and is often incomplete. Here, the decomposition of three types of biodegradable bags and one type of plastic bag in different types of environments was analyzed. Polymer bags were exposed for six weeks in water, soil, air and compost, while the control groups were stored in room conditions. All types of polymer bags were sampled twice (after 3 and 6 weeks), and different parameters of changes in physical–mechanical properties were measured. The research established significant differences in changes in mechanical properties between different types of biodegradable polymer bags, with ‘white’ and ‘brown’ bags showing the best decomposition potential. As expected, the largest change in the structure and physical–mechanical properties of all types of polymer bags was recorded in compost, and the smallest in air and water.

Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study.

We aimed to investigate changes in pre-diagnostic concentrations of classic and 11-oxygenated androgens in type 2 diabetes (T2DM) cases and healthy controls, associations between androgen concentrations and T2DM, and the potential for androgens to improve the prediction of T2DM when considered in combination with established risk factors. Androgen concentrations were analysed in serum samples from 116 T2DM cases and 138 controls at 3, pre-diagnostic time-points: 1986/87 (T1), 1994/95 (T2), and 2001 (T3). Generalised estimating equations were used to longitudinally examine androgen concentrations, and logistic regression models were used to estimate the odds ratios (OR) of T2DM at each time-point. Logistic regression models were also used to calculate area under the receiver operating characteristics curve (AROC) from models including established risk factors alone (ERF model) and established risk factors plus each androgen, respectively, which were compared to identify improvements in predictive ability. For women, no significant associations were observed between any of the investigated androgens and T2DM after adjusting for confounders. For men, after adjusting for confounders, concentrations of all investigated 11-oxygenated androgens were higher in cases than controls at one or several time-points. We observed associations between T2DM and concentrations of 11-ketoandrostenedione (OR: 1.59) and 11-ketotestosterone (OR: 1.62) at T1; and 11-hydroxyandrostenedione (OR: 2.00), 11-hydroxytestosterone (OR: 1.76), 11-ketoandrostenedione (OR: 1.84), 11-ketotestosterone (OR: 1.78) and testosterone (OR: 0.45) at T3 in men. The addition of these androgens (including 11-hydroxytestosterone at T2) to the ERF model resulted in an improved ability to predict T2DM in men (AROC: 0.79-0.82). We did not observe significant differences in changes in androgen concentrations over time between cases and controls in either sex. Our results demonstrate that testosterone and 11-oxygenated androgens are associated with T2DM in men before diagnosis and may be potential biomarkers in T2DM risk assessment.

Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from abnormal mitochondrial function. Currently, there is no causal treatment for MDs. The aim of the study was to assess the effectiveness and safety of the ketogenic diet (KD) in patients with MD and to analyse selected biochemical and clinical parameters evaluating the effectiveness of KD treatment in patients with MDs. A total of 42 paediatric patients were assigned to four groups: group 1-patients with MD in whom KD treatment was started (n = 11); group 2-patients with MD remaining on an ordinary diet (n = 10); group 3-patients without MD in whom KD treatment was initiated (n = 10), group 4-patients without MD on a regular diet (n = 11). Clinical improvement was observed in 9/11 patients with MD treated with KD. Among patients with MD without KD, the clinical condition deteriorated in 7/10 patients, improved in 2/10 patients, and remained unchanged in one patient. Adverse events of KD occurred with a comparable frequency in groups 1 and 3. There was no significant difference in changes in biomarker concentrations over the course of the study among patients treated and untreated with KD.

Efficacy of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke: a predefined exploratory analysis of a multicenter, double-blind, randomized controlled trial.

Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome in patients with acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on cognitive function in patients with AIS. This is a predefined exploratory analysis of the Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial, which was primarily designed to investigate the efficacy and safety of GDLM versus placebo on functional outcome at 100 centers in China. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. The primary outcomes were changes of MoCA from baseline to Day 14 and Day 90 after randomization. A total of 3163 patients with completed data on MoCA were enrolled. There was statistically significant difference of changes in MoCA scores between the GDLM group and the placebo group from baseline to Day 14 (mean difference, 0.31; 95% confidence interval [CI], 0.08-0.53; P = 0.007) and to Day 90 after randomization (mean difference, 0.47; 95% CI, 0.22-0.72; P < 0.001). Additionally, GDLM was associated with a higher proportion of patients who reached a clinically significant level of improvement in MoCA from baseline to Day 14 (odds ratio [OR], 1.25; 95% CI, 1.08-1.44; P = 0.002) and Day 90 after randomization (OR, 1.21; 95% CI, 1.03-1.41; P = 0.02). Specially, GDLM could significantly improve the scores of visuo-spatial and executive function and language. In this predefined analysis of patients with AIS, GDLM could improve the 14-day and 90-day cognitive function compared with the placebo.

Distal Versus Proximal Radial Artery Access for Cardiac Catheterization: 1-Year Outcomes

Proximal radial artery (PRA) access for cardiac catheterization is safe but can jeopardize subsequent use of the artery because of occlusion. Distal radial artery (DRA) access in the anatomical snuffbox preserves the RA but safety and potential detrimental effects on hand function are unknown. We aimed to assess hand function and complications after DRA and PRA. In this single-center trial, 300 patients were randomly allocated 1:1 to cardiac catheterization through DRA or PRA. The primary end point of change in hand function from baseline to 1 year was a composite of the Quick Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, hand grip test, and thumb-forefinger pinch test. The secondary end points included access feasibility and complications. Of 216 patients with 1-year completed follow-up, 112 were randomly allocated to DRA and 104 to PRA, with balanced demographics and procedural characteristics. Both groups had similar access site bleeding rates (DRA 0% vs PRA 1.4%, p = 0.25). Radial artery occlusion occurred in 1 PRA patient versus 2 in DRA. There was no significant difference in change of hand function, median (interquartile range) hand grip (DRA 0.7 [-3 to 4.5] vs PRA 1.3 [-2 to 4.3] kg, p = 0.57), pinch grip (DRA -0.1 [-1.1 to 1] vs PRA -0.3 [-1 to 0.7] kg, p = 0.66), and Quick DASH (DRA 0 [-6.6 to 2.3] vs PRA 0 [-4.6 to 2.9] points, p = 0.58). The composite of hand function was comparable between PRA and DRA. In conclusion, DRA is a safe strategy for cardiac catheterization, with a low complication rate. Compared with PRA, there is no increased risk of hand dysfunction or radial artery occlusion at 1 year.

Comparing Impact of Overactive Bladder Therapies on Nocturia.

Nocturia is a significant symptom in overactive bladder with little data regarding the impact of overactive bladder treatments on nocturia. Compare the effect of anticholinergic (AC) medication, onabotulinum toxin A (BTX), and sacral neuromodulation (SNM) on nocturia. Secondary analysis of the ABC and ROSETTA trials using data from the National Institutes of Health Data and Specimen Hub database. Patients reporting mean ≥2 voids/night on 3-day diary were included and divided into cohorts by treatment: the ABC trial: (1) AC and (2) BTX 100 units, and the ROSETTA trial: (3) BTX 200 units and (4) SNM. Primary outcome was change in mean voids/night on 3-day diary from baseline to 6 months assessed by mixed-effects models for repeated-measures data with interaction between treatment cohort and time included in model. A total of 197 patients were included: 43 (22%) AC, 37 (19%) BTX 100 U, 63 (32%) BTX 200 U, and 54 (27%) SNM. There were no significant differences in baseline voids/night, demographics, or urodynamic values except for younger age in AC and BTX 100 U cohorts (P = 0.04). At 6 months, all cohorts demonstrated a mean 41% decrease in mean voids/night (2.7 ± 0.4 at baseline to 1.6 ± 0.5 at 6 months; P < 0.001), with no significant difference in change in mean voids/night between treatment cohorts (decrease of 44% in AC, 46% in 100 U BTX, 32% 200 in U BTX, and 33% in SNM; P > 0.05). For women with nocturia ≥2/night, treatment with AC, BTX 100 or 200 units, or SNM led to a significant decrease in voids/night at 6 months.

Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n=29) or control diet group (n=32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial.

Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. The 24-week, randomised, double-blind, placebo-controlled, phase 2b portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomised to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in ISS7 at Week 12. The key secondary endpoint was change from baseline in UAS7 at Week 12. Additional secondary endpoints included other metrics to assess CSU at Week 24; blood eosinophil levels; and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. Of 155 patients, 59 were randomised to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% confidence interval -4.09 to 0.50) nor in change from baseline in UAS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.4016; benralizumab 60 mg vs. placebo, P = 0.0819). Depletion of blood eosinophil levels was observed at Week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

High-flow nasal cannula oxygen versus noninvasive ventilation for the management of acute cardiogenic pulmonary edema: a randomized controlled pilot study.

Whether high-flow nasal oxygen can improve clinical signs of acute respiratory failure in acute heart failure (AHF) is uncertain. To compare the effect of high-flow oxygen with noninvasive ventilation (NIV) on respiratory rate in patients admitted to an emergency department (ED) for AHF-related acute respiratory failure. Multicenter, randomized pilot study in three French EDs. Adult patients with acute respiratory failure due to suspected AHF were included. Key exclusion criteria were urgent need for intubation, Glasgow Coma Scale <13 points or hemodynamic instability. Patients were randomly assigned to receive high-flow oxygen (minimum 50 l/min) or noninvasive bilevel positive pressure ventilation. The primary outcome was change in respiratory rate within the first hour of treatment and was analyzed with a linear mixed model. Secondary outcomes included changes in pulse oximetry, heart rate, blood pressure, blood gas samples, comfort, treatment failure and mortality. Among the 145 eligible patients in the three participating centers, 60 patients were included in the analysis [median age 86 (interquartile range (IQR), 90; 92) years]. There was a median respiratory rate of 30.5 (IQR, 28; 33) and 29.5 (IQR, 27; 35) breaths/min in the high-flow oxygen and NIV groups respectively, with a median change of -10 (IQR, -12; -8) with high-flow nasal oxygen and -7 (IQR, -11; -5) breaths/min with NIV [estimated difference -2.6 breaths/min (95% confidence interval (CI), -0.5-5.7), P = 0.052] at 60 min. There was a median SpO2 of 95 (IQR, 92; 97) and 96 (IQR, 93; 97) in the high-flow oxygen and NIV groups respectively, with a median change at 60 min of 2 (IQR, 0; 5) with high-flow nasal oxygen and 2 (IQR, -1; 5) % with NIV [estimated difference 0.8% (95% CI, -1.1-2.8), P = 0.60]. PaO2, PaCO2 and pH did not differ at 1 h between groups, nor did treatment failure, intubation and mortality rates. In this pilot study, we did not observe a statistically significant difference in changes in respiratory rate among patients with acute respiratory failure due to AHF and managed with high-flow oxygen or NIV. However, the point estimate and its large confidence interval may suggest a benefit of high-flow oxygen. NCT04971213 (https://clinicaltrials.gov).

Effect of Intradialytic Exercise on Cardiovascular Outcomes in Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Cardiovascular disease is the leading cause of death among people with kidney failure on hemodialysis, for whom improving cardiovascular health is a research priority. Intradialytic myocardial stunning is common and associated with adverse cardiovascular events. Intradialytic exercise may mitigate intradialytic myocardial stunning and improve cardiovascular structure and function. This systematic review investigated the effect of intradialytic exercise on cardiovascular outcomes in adults undergoing maintenance hemodialysis (PROSPERO #CRD42018103118). Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, SportDiscus, and PEDro databases from 1960 until June 2022, for randomized and non-randomized studies investigating the effect of intradialytic exercise programs on objective cardiovascular outcomes, pre-specified as primary or secondary outcomes. The primary outcome was arterial resistance. Of 10837 references identified, 32 met eligibility criteria. These studies investigated the effect of intradialytic exercise on arterial resistance (8 studies), blood pressure (20 studies), myocardial structure and function (7 studies), endothelial function (2 studies), sympathetic overactivity (9 studies), biomarkers of cardiac injury (3 studies), cardiovascular hospitalization and mortality (2 studies). Most studies used aerobic exercise as the intervention and usual care (no exercise) controls. Meta-analysis of intradialytic exercise versus usual care resulted in a statistically significant reduction in arterial resistance measured by pulse wave velocity (PWV) with mean difference -1.63 m/sec (95% CI -2.51, -0.75). Meta-analyses for diastolic blood pressure, left ventricular ejection fraction (LVEF), and low-frequency/high-frequency (LF/HF ratio) measure of heart rate variability also showed statistically significant improvements with exercise. There was no significant difference in change in systolic blood pressure, augmentation index, and left ventricular mass index between groups. Intradialytic exercise programming resulted in a clinically meaningful improvement to PWV, a component of arterial resistance. Sseveral physiologic measures of cardiovascular health, including diastolic blood pressure, LVEF and heart rate variability measured by the LF/HF ratio were also observed. The effects of intradialytic exercise on major adverse cardiovascular events remains uncertain.

Anterior vs Posterior Surgery for Patients With Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

The advantages and disadvantages of anterior vs posterior surgical approaches for patients with progressive degenerative cervical myelopathy (DCM) remain uncertain. Our primary objective was to evaluate patient-reported disability at 1 year after surgery. Our secondary objectives were to evaluate differences in patient profiles selected for each approach in routine clinical practice and to compare neurological function, neck and arm pain, health-related quality of life, adverse events, and rates of reoperations. We analyzed data from patients with DCM who were enrolled in an ongoing multicenter prospective observational cohort study. We controlled for differences in baseline characteristics and numbers of spinal levels treated using multivariable logistic regression. Adverse events were collected according to the Spinal Adverse Events Severity protocol. Among 559 patients, 261 (47%) underwent anterior surgery while 298 (53%) underwent posterior surgery. Patients treated posteriorly had significantly worse DCM severity and a greater number of vertebral levels involved. After adjusting for confounders, there was no significant difference between approaches for odds of achieving the minimum clinically important difference for the Neck Disability Index (odds ratio 1.23, 95% CI 0.82 to 1.86, P = .31). There was also no significant difference for change in modified Japanese Orthopedic Association scores, and differences in neck and arm pain and health-related quality of life did not exceed minimum clinically important differences. Patients treated anteriorly experienced greater rates of dysphagia, whereas patients treated posteriorly experienced greater rates of wound complications, neurological complications, and reoperations. Patients selected for posterior surgery had worse DCM and a greater number of vertebral levels involved. Despite this, anterior and posterior surgeries were associated with similar improvements in disability, neurological function, pain, and quality of life. Anterior surgery had a more favorable profile of adverse events, which suggests it might be a preferred option when feasible.

Arthroscopic Surgery Versus Nonoperative Treatment for Calcific Tendinitis of the Shoulder: A Retrospective Cohort Study

Background: Treatment options for calcific tendinitis (CT) of the shoulder remain controversial. A consensus for an operative indication for this condition is lacking. Purpose: To compare nonoperative versus operative treatment for shoulder CT and analyze factors affecting the prognosis after treatment. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 180 patients diagnosed with symptomatic CT between January 2017 and September 2021 were evaluated in this retrospective cohort study. There were 103 patients treated nonoperatively at our institution, which included the use of nonsteroidal anti-inflammatory drugs, acupuncture, steroid injections, extracorporeal shock wave therapy, and ultrasound-guided needle aspiration/percutaneous irrigation. However, 77 patients were treated with arthroscopic surgery after 6 months of failed nonoperative treatment. The visual analog scale (VAS) for pain, the Constant-Murley score, and imaging were used to assess and evaluate outcomes. Descriptive data, functional outcomes, and imaging findings were compared between the operative and nonoperative groups before and after propensity score matching. Additionally, prognostic factors including calcium deposit size, tendon infiltration by calcium deposits, involvement of single or multiple tendons, and occurrence of rotator cuff tears were analyzed by comparing the groups to determine their effect on treatment options and recovery. Results: Magnetic resonance imaging showed that the supraspinatus tendon (66.7%) was most commonly involved, followed by the infraspinatus (42.8%) and subscapularis (21.1%) tendons. Tendon infiltration by calcium deposits was observed in 84.4% of the patients, and rotator cuff tears occurred in 30.0% of the patients. After propensity score matching, there was no significant difference in changes in the Constant-Murley score (48.1 ± 25.4 vs 49.0 ± 22.8, respectively; P = .950) and VAS score (4.9 ± 2.3 vs 4.5 ± 1.9, respectively; P = .860) between the operative and nonoperative groups at the final follow-up. However, for patients with shoulder CT and without rotator cuff tears, there was a significant difference in changes in the Constant-Murley score (52.93 ± 25.18 vs 42.13 ± 22.35, respectively; P = .012) and VAS score (5.21 ± 2.06 vs 3.81 ± 1.98, respectively; P < .001) between the operative and nonoperative groups, but the recovery time in the operative group was longer than that in the nonoperative group (86.92 ± 138.56 vs 30.42 ± 54.97 days, respectively; P = .016). The results also showed that calcium deposit size, involvement of multiple tendons, and tendon infiltration by calcium deposits did not affect the recovery time after treatment. The survival analysis showed that rotator cuff tears affected the complete recovery of shoulder function. Conclusion: This study demonstrated no significant difference between nonoperative and operative treatment for patients with shoulder CT, on the whole. However, for patients with shoulder CT and without rotator cuff tears, the effect of operative treatment was better than that of nonoperative treatment; yet, operative treatment was shown to prolong the recovery time. Calcium deposit size, tendon infiltration by calcium deposits, and involvement of multiple tendons did not correlate with recovery time or the recovery of function. A rotator cuff tear was the only factor affecting the complete recovery of shoulder function.

Automatic Mechanical Ventilation vs Manual Bag Ventilation During CPR: A Pilot Randomized Controlled Trial

BackgroundThere is insufficient evidence supporting that mechanical ventilation can replace the manual ventilation method during cardiopulmonary resuscitation (CPR). Research QuestionIs using automatic mechanical ventilation feasible and comparable to the manual ventilation method during CPR? Study Design and MethodsThis is a pilot randomized controlled trial comparing automatic mechanical ventilator (MV) and manual bag ventilation (BV) during CPR of out-of-hospital cardiac arrest (OHCA). Patients with medical OHCA arriving at the emergency department were randomly assigned to two groups: an MV group using a mechanical ventilator and a BV group using Ambu-bag. Primary outcome was any return-of-spontaneous circulation (ROSC). Secondary outcomes were changes of arterial blood gas analysis results during CPR. Tidal volume, minute volume, and peak airway pressure were also analyzed. ResultsA total of 60 patients were enrolled and 30 patients were randomly assigned to each group. There were no statistically significant differences in basic characteristics of OHCA patients between the two groups. The rate of any ROSC was 56.7% in the MV group and 43.3% in the BV group, showing no significant (p = 0.439) difference between the two groups. There were no statistically significant differences in changes of PH, PCO2, PO2, HCO3, or lactate level during CPR between the two groups either (p-value: 0.798, 0.249, 0.515, 0.876. and 0.878, respectively). Significantly lower TV (p < 0.001) and minute volume (p = 0.009) were found in the MV group. InterpretationIn this pilot trial, the use of MV instead of BV during CPR was feasible and could serve as a viable alternative. A multicenter RCT is needed to create sufficient evidence for ventilation guideline during CPR.