Days Of Therapy Research Articles

Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease.

Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach. We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD. Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on-demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on-demand dosing and sustained for 24 h. Of 458 patients in the run-in period, 207 entered the on-demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group (p < 0.0001 versus placebo for each vonoprazan group). By 1 h post-dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment-emergent adverse events were reported. On-demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD. gov: NCT04799158.

Effect of virtual reality combined with repetitive transcranial magnetic stimulation on musculoskeletal pain and motor development in children with spastic cerebral palsy: a protocol for a randomized controlled clinical trial

PurposeThis trial aims to investigate the efficacy and safety of virtual reality (VR) combined with repetitive transcranial magnetic stimulation (rTMS) for improving musculoskeletal pain and motor development in children with unilateral spastic cerebral palsy (CP).MethodsThis study protocol is for a randomized controlled trial consisting of 2 treatment sessions (3 days/week for 4 weeks in each session, with a 1-week interval between sessions). We will recruit children aged 3–10 years with unilateral spastic CP (Gross Motor Function Classification System level I or II). Participants will be randomly divided into 3 groups: the VR + rTMS group (immersive VR intervention, rTMS and routine rehabilitation therapy), rTMS group (rTMS and routine rehabilitation therapy), and control group (sham rTMS and routine rehabilitation therapy). VR therapy will involve a daily 40-minute movement training session in a fully immersive environment. rTMS will be applied at 1 Hz over the primary motor cortex for 20 min on the contralateral side. The stimulation intensity will be set at 90% of the resting motor threshold, with 1200 pulses applied. A daily 60-minute routine rehabilitation therapy session including motor training and training in activities of daily living will be administered to all participants. The primary outcome will be pain intensity, assessed by the Revised Face, Legs, Activity, Cry, and Consolability Scale (R-FLACC). The secondary outcomes will include motor development, evaluated by the 66-item version of the Gross Motor Function Measure (GMFM-66) and Fine Motor Function Measure (FMFM); balance capacity, measured by the interactive balance system; activities of daily living; and quality of life, measured by the Barthel index and the Chinese version of the Cerebral Palsy Quality of Life scale for Children (C-CP QOL-Child). Safety will be monitored, and adverse events will be recorded during and after treatment.DiscussionCombined application of VR therapy and rTMS may reveal additive effects on pain management and motor development in children with spastic CP, but further high-quality research is needed. The results of this trial may indicate whether VR therapy combined with rTMS achieves a better analgesic effect and improves the motor development of children with spastic CP.Trial registrationRegistration number: ChiCTR230069853. Trial registration date: 28 March 2023. Prospectively registered.

Assessing Time in Range with Postprandial Glucose-Focused Titration of Ultra Rapid Lispro (URLi) in People with Type1 Diabetes.

To assess time in range (TIR) (70-180mg/dL) with postprandial glucose (PPG)-focused titration of ultra rapid lispro (URLi; Lyumjev®) in combination with insulin degludec in people with type1 diabetes (T1D). This phase2, single-group, open-label, exploratory study was conducted in 31 participants with T1D on multiple daily injection therapy. Participants were treated with insulin degludec and Lispro for an 11-day lead-in and then URLi for a 46-day treatment period consisting of 35-day titration and 11-day endpoint maintenance period. Glucose targets for the titration period were PPG < 140mg/dL or < 20% increase from premeal, fasting glucose 80-110mg/dL, and overnight excursion ± 30mg/dL or less. Participants used the InPen™ bolus calculator and Dexcom G6 continuous glucose monitoring (CGM). Primary endpoint mean TIR (70-180mg/dL) with URLi during the maintenance period was 70.2%. TIR (70-180mg/dL) and times below/above range were not significantly different with URLi (maintenance) versus lispro (lead-in). HbA1c decreased from 7.1% at screening to 6.8% at endpoint (least squares mean [LSM] change from baseline, - 0.36%; P < 0.001). Fructosamine and 1,5-anhydroglucitol improved (P < 0.001). Mean hourly glucose using CGM was reduced from 8:00AM to 4:00PM with URLi. Overall highest PPG excursion across meals was significantly reduced at URLi endpoint compared with lispro lead-in (mean 56.5 vs 72.4mg/dL; P < 0.001). Insulin-to-carbohydrate ratio (U/Xg) was reduced (more insulin given) at breakfast at URLi endpoint vs lead-in (LSM 9.0 vs 9.7g; P = 0.002) and numerically decreased at other meals. Total daily insulin dose (TDD) was higher at URLi endpoint compared with lispro lead-in (mean 50.2 vs 47.0U; P = 0.046) with similar prandial/TDD ratio (mean 52.1% vs 51.2%). There were no severe hypoglycemia events during the study. URLi in a basal-bolus regimen focusing on PPG targets demonstrated improved overall glycemic control and reduced PPG excursions without increased hypoglycemia in participants with T1D. ClinicalTrial.gov, NCT04585776.

Investigation of the metabolic and endocrinological differences between daily and weekly growth hormone replacement therapy, somapacitan, in patients with adult growth hormone deficiency: A real-world pilot study.

In this real-world pilot study, we evaluated the metabolic and endocrinological effects in patients with adult growth hormone deficiency (AGHD) who switched from daily growth hormone (GH) replacement therapy to weekly GH replacement therapy using somapacitan. Eleven patients with AGHD, whose medical treatment aside from GH replacement therapy did not change, were enrolled. We investigated the metabolic and endocrinological parameters between at switching and 6 months after switching from daily GH formulation to somapacitan. The results showed that body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and liver functions were significantly improved 6 months after switching compared to those at switching (each P < .05). Besides, the improvement in HOMA-IR was significantly associated with the period of daily GH replacement therapy before switching (P = .048), while age, sex, improvement in BMI or liver functions, presence of any hormonal deficiency, and the existence of any hormonal replacement therapy significantly associated (P > .05). In addition, switching to GH replacement therapy did not affect endocrinological parameters. In conclusion, this study might indicate that weekly GH replacement therapy with somapacitan could have more beneficial points than daily GH replacement therapy. Considering the cohort of this study was small, future studies with larger cohorts should be necessary to confirm the results of this study.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study

Background and purposePneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. MethodsThis retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. ResultsThe cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = −0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = −0.006, p = 0.787 and rs = −0.156, p = 0.398). ConclusionAfter the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.

Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by − 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96–1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16–5.50), and pneumonia (OR = 2.59, 95% CI 1.08–6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.

14-Day Vonoprazan-Based Bismuth Quadruple Therapy for Treatment-Naïve Patients with Helicobacter pylori Infection: A Retrospective Comparative Study.

Until now, there is little evidence regarding clinical efficacy of 14-day vonoprazan-based bismuth quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication. Overall, 65 treatment-naïve patients with H. pylori infection who received 14-day vonoprazan-based BQT regimen (VBCA, n=17) or pantoprazole-based BQT regimen (PBCA, n=48) for H. pylori eradication were retrospectively included. Neither successful H. pylori eradication (88.2% versus 91.7%, p=1.000) nor adverse event (52.9% versus 64.6%, p=0.397) was significantly different between VBCA and PBCA groups. Vonoprazan seems to be as effective and safe as pantoprazole during a 14-day BQT regimen in treatment-naïve patients with H. pylori infection.

Study of Pentraxin-3 as an Early Marker of Diabetic Vascular Complications in Children and Adolescents with Type 1 Diabetes Mellitus

Background Vascular complications are the major cause of morbidity and mortality in diabetic patients. These can result from interactions between systemic metabolic abnormalities, such as hyperglycemia, dyslipidemia, genetic and epigenetic modulators, and local tissue responses to toxic metabolites. Aim of the Work To assess the role of PTX3 as an early marker of vascular complications in children and adolescents with type 1 diabetes mellitus and its correlation with metabolic control and its relation to hsCRP level. Patients and Methods Fifty adolescents with type 1 diabetes mellitus and 40 age and sex matched control group, Detailed history taking, full systemic examination were done, Patients also were investigated using HbA1c, lipid profile, ALT, Alb/Cr ratio in urine, PTX3, hsCRP and carotid intima media thickness (CIMT). An informed consent was obtained from patients, controls or their legal guardians before enrollment in the study. Inclusion criteria Patients with type 1 diabetes their age ranging from 5 to 18 years old with at least 5 years disease duration and on regular clinic visits and multiple daily insulin therapy . Exclusion criteria Patients with proven vascular complications and those with any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases, also patients with morbid obesity were excluded. Results PTX3 and hsCRP were significantly higher in patients compared to control group. A significant positive correlation between serum PTX3 and level of HbA1c%, level of Triglycerides (TG), level of Total Cholesterol was observed. Additionally, PTX3 and hsCRP levels were elevated in patients with elevated lipid profile (TG and Cholesterol) and high HbA1c% level in comparison with those with normal lipid profile and those with controlled HbA1c% level (p &amp;lt; 0.001). No significant difference was found between patients and control groups as regard CIMT. Conclusion . The increased levels of PTX3 and hsCRP in patients with uncontrolled diabetes even before development of both microvascular and macrovascular complications add a promising tool for their follow up and applying early protective measures.

Effects of antimicrobial therapy duration and class on risk of antimicrobial-resistant Gram-negative bacillus bloodstream infection in patients with AML.

Antimicrobial-resistant Gram-negative bacilli (ARGNB) bloodstream infection (BSI) has been associated with prior antibiotic exposure among hematologic malignancy patients. The relationships between days of therapy (DOT), antimicrobial class, and ARGNB BSI risk are poorly understood. This is a single-center, case-control study of acute myeloid leukemia (AML) patients including 115 cases with ARGNB BSI and 230 matched controls with non-ARGNB BSI between January 1, 2007 and December 31, 2018. Fixed- and mixed-effects logistic regression was used to examine relationships between antibiotic DOT and risk of ARGNB BSI. Admission to an intensive care unit (ICU) within 7 days, 30-day mortality, and Pitt Bacteremia Score (PBS) were secondary outcomes. Prior isolation of a antimicrobial-resistant organism (ARO) (OR 4.45 95% CI 1.46, 13.54), surgery within 90 days (OR 3.71, 95% CI 1.57, 8.73), aminoglycoside DOT (OR 1.14, 95% CI 1.05, 1.23), cefepime DOT (OR 1.09, 95% CI 1.05, 1.13), and carbapenem DOT (OR 1.10, 95% CI 1.05, 1.16) were associated with increased odds of ARGNB BSI. Days since last antibiotic administration (OR 0.98, 95% CI 0.97, 0.99) and inpatient days within 90 days (OR 0.95, 95% CI 0.93, 0.98) showed reduced odds of ARGNB BSI. Total antimicrobial DOT regardless of class was not associated with ARGNB BSI. ARGNB BSI was associated with increased 30-day mortality (OR 2.86, 95% CI 1.57, 5.22) CONCLUSIONS: Among AML patients with GNB BSI, greater DOT of aminoglycosides, cefepime, and carbapenems in the 90 days prior to BSI were associated with increased odds of ARGNB BSI.

Real-world Evidence for Impact of Opioid Agonist Therapy on Nonfatal Overdose in Patients with Opioid Use Disorder during the COVID-19 Pandemic.

The primary objectives of this study were to describe the demographics and clinical characteristics of patients who were treated with buprenorphine extended-release versus buprenorphine-naloxone sublingual tablets versus methadone in a real-world setting and to evaluate the difference in nonfatal overdose events between treatment cohorts. This study was a retrospective chart review of patients with opioid use disorder initiating opioid agonist therapy in Canada during the outset of the COVID-19 pandemic (March 11, 2020 to October 31, 2021). Three treatment cohorts were defined by the initial prescribed opioid agonist therapy regimen: buprenorphine extended-release, buprenorphine-naloxone sublingual tablets, and methadone. Baseline characteristics, as well as treatment status, overdose events, and substance use 6 months after treatment initiation were collected using a standardized form. Nine clinics provided data on 379 patient cases. The incidence rate (number of events per 100 person-years) for a self-reported nonfatal overdose was 46.8 (n = 18), 19.3 (n = 10), and 1.7 (n = 1) in the methadone, buprenorphine-naloxone sublingual tablets, and buprenorphine extended-release cohorts, respectively. The risk-adjusted difference for the proportion of patients with nonfatal overdose was 8.59% (95% confidence interval, 3.10-14.08%; P = 0.0022) for methadone versus buprenorphine extended-release and 6.51% (95% confidence interval, 1.46-11.56%; P = 0.0115) for buprenorphine-naloxone sublingual tablets versus buprenorphine extended-release. Buprenorphine extended-release was associated with lower rates of nonfatal overdose events compared with daily opioid agonist therapy. Given the limitations of this naturalistic, retrospective design, further prospective studies are needed to validate these findings and demonstrate the potential for long-acting opioid agonist therapy in addressing the opioid crisis.

Impact of multiplex polymerase chain reaction syndromic panel on antibiotic use among hospitalized children with respiratory tract illness during COVID-19 pandemic.

Precise detection of respiratory pathogens by molecular method potentially may shorten the time to diagnose and reduce unnecessary antibiotic use. Medical records of hospitalized children from January 2020 to June 2021 with acute respiratory illness who received a FilmArray RP for respiratory pathogens were reviewed and compared with data from diagnosis-matched patients without receiving the test. In total, 283 patients and 150 diagnosis-matched controls were included. Single pathogen was detected in 84.3% (193/229) of the patients. The most common pathogen was human rhinovirus/enterovirus (31.6%, 84/266), followed by respiratory syncytial virus (18.8%, 50/266) and adenovirus (15%, 40/266). Although antimicrobial days of therapy (DOT) was significantly longer in FilmArray group than the control [7.1±4.9 days vs 5.7±2.7 days, P=0.002], the former showed a higher intensive care unit (ICU) admission rate (3.9% vs 0%; P=0.010). All ICU admissions were in FilmArray RP-positive group. There was no difference in antimicrobial DOT between FilmArray RP-positive and the negative groups, in all admissions, even after excluding ICU admissions. Antimicrobial DOT was shorter in the positive than negative group in patients with lower respiratory tract infections without admission to ICU [median (IQR): 6 (4-9) days vs 9 (4-12) days, P=0.047]. Shorter antimicrobial DOTs were identified in children with lower respiratory tract infection admitted to general pediatric ward and with an identifiable respiratory pathogen, indicating a role of the multiplex PCR in reducing antimicrobial use for children with respiratory tract infection.

"It's real. It's a thing:" Mental health counselors' listening exhaustion during COVID-19.

Mental health counselors regularly use active listening skills to be present with each client; however, active listening may cause burnout due to high emotional labor, inadequate staffing, excessive workload, and many other issues, each of which contributes to career exits. COVID-19 exacerbated all of these factors, and-adding to already stressful conditions-most mental health professionals were forced to conduct therapy sessions via telehealth. For this study, twenty licensed mental health counselors at various stages of their careers were interviewed during the height of the pandemic to understand their experiences with the technology and other factors related to their workload during that time. Thematic qualitative analysis was used to explore effects of active listening-including requisite adjustments made for virtual therapy sessions-on counselors' emotional exhaustion and burnout levels. Results show how back-to-back, daily therapy sessions increased listening exhaustion levels and that counselors experienced both long-term and short-term listening exhaustion when utilizing telehealth due to lack of nonverbal cues and other related factors pertaining to online delivery. Implications for counselors, social workers, and other mental health professionals are discussed.

A day-to-day management model improves patient compliance to treatment for Helicobacter pylori infection: a prospective, randomized controlled study

BackgroundThe day-to-day (DTD) management model encourages patients to actively participate in their healthcare by setting goals. We determined the effectiveness of the DTD model in the treatment of Helicobacter pylori (H. pylori) infection, as compared with conventional outpatient education (OE).MethodsWe randomized 254 H. pylori-positive patients into a DTD group (127 patients) and an OE group (127 patients) prior to primary treatment with 14-day bismuth-containing quadruple therapy, including esomeprazole, amoxicillin, and clarithromycin. Both groups received consistent medication instructions. Patients in the DTD group recorded daily attendance after completing their daily medication plan from day 1 to day 14. The medication compliance, follow-up compliance, H. pylori eradication rates, and adverse events (AEs) were evaluated.ResultsIn the modified intention-to-treat (MITT) and per-protocol (PP) analyses, the DTD group showed significantly higher medication compliance than the OE group (P = 0.001 and P = 0.031, respectively). Both the MITT and PP analyses showed significant differences in follow-up compliance (P < 0.001 and P = 0.003, respectively) and timing of the review urea breath test (P < 0.001 and P = 0.001, respectively) between the two groups. However, no significant differences were observed in the H. pylori eradication rates (95.8% vs. 93.8%, P = 0.529) in the PP analysis, or AEs incidence (25.4% vs. 28.3%, P = 0.603) between the two groups.ConclusionThis study demonstrated the novel application of the DTD model in the treatment of H. pylori infection, which enabled patients to develop habitual medication-taking behaviors without physician intervention.

Association between daily aspirin therapy and risk of hepatocellular carcinoma according to metabolic risk factor burden in non-cirrhotic patients with chronic hepatitis B.

Several studies have demonstrated chemopreventive effects of aspirin against hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). To investigate the associations of aspirin use with risks of HCC, liver-related mortality, and major bleeding according to metabolic risk factor burden among non-cirrhotic patients with CHB METHODS: Using the Korean National Health Insurance Service database, we identified 282,611 non-cirrhotic adults with CHB. Data on obesity, diabetes, high blood pressure, and hypercholesterolemia were collected. Subjects were stratified into lower and higher metabolic risk groups (≤2 and ≥3 risk factors, respectively). Propensity score-matched cohorts of aspirin users and non-users were generated. Risks of HCC, liver-related death and major bleeding were analyzed. During the median follow-up of 7.4 years, positive associations between metabolic risk factor burden and outcomes were verified (all ptrend < 0.001). In the lower metabolic risk group (13,104 pairs), the association between aspirin use and HCC risk was not significant after multivariable adjustment (adjusted subdistribution hazard ratio [aSHR]: 0.93; 95% CI: 0.84-1.03); however, aspirin use was associated with elevated major bleeding risk (aSHR: 1.22; 95% CI: 1.08-1.39). In the higher metabolic risk group (2984 pairs), aspirin use was associated with reduced risks of HCC (aSHR: 0.72; 95% CI: 0.57-0.91) and liver-related mortality (aSHR: 0.69; 95% CI: 0.50-0.96) without an increase in risk of major bleeding (aSHR: 1.02; 95% CI: 0.79-1.32). Aspirin therapy was associated with reduced risks of HCC and liver-related death without excess risk of major bleeding, in non-cirrhotic patients with CHB who had a higher metabolic risk factor burden.

The Prevalence and Risk Factors of Acute Kidney Injury during Colistin Therapy: A Retrospective Cohort Study from Lebanon.

The current study aimed to determine the prevalence, risk factors, and stages of severity of acute kidney injury (AKI) caused by colistimethate sodium (CMS) treatment in patients diagnosed with systemic antibiotic-resistant Gram-negative bacterial infections. The predictors of all-cause mortality in this patient population were also examined. This retrospective cohort study included patients who were admitted to a university-affiliated hospital and acute tertiary care referral center in Beirut, Lebanon between January 2015 and December 2018 and underwent CMS treatment for a period of 48 h or more. The study sample included 298 adult patients, of which 46.3% (n = 138/298) developed AKI (assessed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria). Of these, 37.7% (n = 51/138) were diagnosed with stage 1 AKI, 23.9% with stage 2 (n = 33/138), and 38.4% with stage 3 (n = 53/138). Nephrotoxicity was reversed in 87.5% of AKI patients who survived until hospital discharge. Independent risk factors for AKI included patient age ≥ 75 years (aOR = 1.854; 95% CI: 1.060-3.241; p-value = 0.03); underlying chronic kidney disease (aOR = 4.849; 95% CI: 2.618-9.264; p-value < 0.0001); and concomitant use of vasopressors (aOR = 4.305; 95% CI: 2.517-7.456; p-value < 0.0001). Multivariate analysis showed that the predictors of severe AKI (stage 2 or 3) included baseline hypoalbuminemia (aOR = 2.542; 95% CI: 1.000-6.564; p-value = 0.05); concomitant use of vasopressors (aOR = 6.396; 95% CI: 2.741-15.87; p-value < 0.0001); and CMS days of therapy (DOT) prior to development of AKI ≥ 7 days (aOR = 4.728; 95% CI: 2.069-11.60; p-value < 0.0001). All-cause mortality was recorded in 51.3% of patients (n = 153/298), and this was significantly higher in patients with AKI (76.8%; n = 106/138) compared to those without (29.4%; n = 47/160; OR = 7.964; 95% CI: 4.727-13.417; p-value < 0.0001). Independent predictors of all-cause mortality included a baseline Charlson comorbidity index score ≥5 (aOR = 4.514; 95% CI: 2.443-8.530; p-value < 0.0001); concomitant use of vasopressors (aOR = 7.76; 95% CI: 4.238-14.56; p-value < 0.0001); and CMS-induced AKI (aOR = 4.117; 95% CI: 2.231-7.695; p-value < 0.0001). The findings of this study suggest that old age, history of chronic kidney disease, and concomitant vasopressor treatment are all independent predictors of CMS-induced AKI. The risk of developing severe AKI significantly increases with CMS DOT. Understanding the risk factors of nephrotoxicity is essential for improving prognosis and treatment outcomes.

Effects of Acupotomy on Immobilization-Induced Gastrocnemius Contracture and Fibrosis in Rats via Wnt/β-Catenin Signaling.

To determine whether acupotomy ameliorates immobilization-induced muscle contracture and fibrosis via Wnt/β-catenin signaling pathway. Thirty Wistar rats were randomly divided into 5 groups (n=6) by a random number table, including control, immobilization, passive stretching, acupotomy, and acupotomy 3 weeks (3-w) groups. The rat model of gastrocnemius contracture was established by immobilizing the right hind limb in plantar flexion for 4 weeks. Rats in the passive stretching group received passive stretching at gastrocnemius, a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days. Rats in the acupotomy and acupotomy 3-w groups received acupotomy once and combined with passive stretching at gastrocnemius a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days. Additionally, rats in the acupotomy 3-w group were allowed to walk freely for 3 weeks after 10-day therapy. After treatment, range of motion (ROM), gait analysis [i.e., paw area, stance/swing and maximum ratio of paw area to paw area duration (Max dA/dT)], gastrocnemius wet weight and the ratio of muscle wet weight to body weight (MWW/BW) were tested. Gastrocnemius morphometric and muscle fiber cross-sectional area (CSA) were assessed by hematoxylin-eosin staining. Fibrosis-related mRNA expressions (i.e., Wnt 1, β-catenin, axin-2, α-smooth muscle actin, fibronectin, and types I and III collagen) were measured using real-time quantitative polymerase chain reactions. Wnt 1, β-catenin and fibronectin concentrations were measured by enzyme-linked immunosorbent assay. Types I and III collagen in the perimysium and endomysium were analyzed using immunofluorescence. Compared with the control group, ROM, gait function, muscle weight, MWW/BW and CSA were significantly decreased in the immobilization group (all P<0.01), while protein levels of types I and III collagen, Wnt 1, β-catenin, fibronectin and mRNA levels of fibrosis-related genes were obviously increased (all P<0.01). Treatment with passive stretching or acupotomy restored ROM and gait function and increased muscle wet weight, MWW/BW and CSA (all P<0.05), while protein expression levels of Wnt 1, β-catenin, fibronectin, types I and III collagen and mRNA levels of fibrosis-related genes were remarkably declined compared with the immobilization group (all P<0.05). Compared with passive stretching group, ROM, gait function, MWW was remarkably restored (all P<0.05), and mRNA levels of fibrosis-related genes as well as protein expression levels of Wnt 1, β-catenin, fibronectin, types I and III collagen in the acupotomy group were obviously decreased (all P<0.05). Compared with the acupotomy group, ROM, paw area, Max dA/dT, and MWW were restored (all P<0.05), and mRNA levels of fibrosis-related genes along with protein levels of Wnt 1, β-catenin, fibronectin, types I and III collagen in the acupotomy 3-w group were decreased (P<0.05). Improvements in motor function, muscle contractures, and muscle fibrosis induced by acupotomy correlates with the inhibition of Wnt/β-catenin signaling pathway.

Evaluation of an Automated, Pharmacist-Driven, Antimicrobial Patient Acuity Scoring System for Hospitalized Bacteremic Patients.

Purpose: The implementation of an automated, pharmacist-driven, scoring system within the EMR has been shown to improve patient care in patients with Staphylococcus aureus bacteremia by increasing the adherence to disease specific quality-of-care measures. However, there are a lack of studies evaluating the incorporation of blood culture review into standard, non-antimicrobial stewardship pharmacist workflow. Our institution implemented an automated, pharmacist-driven, antimicrobial scoring system in the electronic medical record (EMR) on August 6, 2019. Methods: This was a retrospective, single-center, quasi-experimental study of hospitalized, non-critically ill adult (18-89 years of age) patients with bacteremia between July 6, 2018 and July 5, 2019 (pre-implementation group) and September 6, 2019 and September 5, 2020 (post-implementation group). The primary outcome was time to directed antibiotic therapy in patients with positive blood cultures. Secondary outcomes included hospital length-of-stay, days of therapy (DOT) while inpatient, time to effective therapy, 30-day all-cause mortality, and rates of Clostridioides difficile infections documented within 3 months of positive culture results. Results: Implementation of the antimicrobial scoring system did not result in a significant change in time to directed antibiotic therapy (32.5 hours vs 37.4 hours; P = .757). There was also no difference found for time to effective antibiotic therapy (-12.6 hours vs -14.2 hours; P =.905) and no difference found for all other secondary outcomes. Conclusion: The implementation of the antimicrobial scoring system did not lead to an improvement in clinical outcomes. Further research is needed to better define a patient population that may benefit from this system.

Ten-day tegoprazan-based concomitant therapy as a first-line treatment for Helicobacter pylori eradication.

Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a tegoprazan-based, nonbismuth-containing quadruple (concomitant) therapy for the primary eradication of Helicobacter pylori. We conducted a prospective, single-arm, single-center, primitive study to verify the efficacy of a 10-day tegoprazan- based (50-mg dose) concomitant therapy, including amoxicillin (1,000-mg dose), clarithromycin (CLA; 500-mg dose), and metronidazole (MET; 500-mg dose) twice daily as a first-line treatment for H. pylori eradication. We tested consecutive cultures for antibiotic susceptibility and minimum inhibitory concentrations. We enrolled 84 participants; 79 (94.0%) completed first-line therapy. The overall intention-to-treat and per-protocol eradication rates were 90.5% (95% confidence interval [CI], 82.1-95.8) and 96.2% (95% CI, 83.4-97.6), respectively. Of the 73 participants evaluated for antibiotic resistance, 19 (26.0%), 32 (42.5%), and 8 (11.0%) exhibited CLA, MET, and CLA and MET dual resistance, respectively. Of these, 39 participants (66.1%) exhibited successful eradication after the therapeutic regimen despite antibiotic resistance. The 10-day tegoprazan-based concomitant therapy may be an effective first-line treatment for eradicating H. pylori.

The Effects of Music Intervention on Respiratory Comfort, Anxiety, and Depression During Noninvasive Mechanical Ventilation Among Patients With COVID-19

Background: Hospitalized patients with COVID-19 may experience emotional problems and respiratory discomfort during mechanical ventilation. This study aimed to evaluate the effects of music therapy on respiratory comfort, anxiety, and depression among patients with COVID-19 under noninvasive mechanical ventilation. Methods: It was a randomized clinical trial. The study subjects were 64 patients requiring noninvasive mechanical ventilation (NIV) who were selected from the COVID-19 intensive care unit (ICU) of Ali ibn Abi Talib Hospital, Rafsanjan City, Iran. They were randomly allocated to the intervention (n=32) and control (n=32) groups. The intervention group received 30 minutes of daily light music by an MP3 player and a JBL headphone for 4 consecutive days, and the control group only used headphones. The data were collected by the hospital anxiety and depression scale and a visual analog scale before and 4 days after the intervention. The SPSS software, version 16 was employed for data analysis through the chi-square, independent sample, and paired-samples t-tests at a significance level P&lt;0.05. Results: The groups did not significantly differ regarding the pre-test mean scores of respiratory comfort, anxiety, and depression before intervention (P&gt;0.05). The mean scores of respiratory comfort, anxiety, and depression significantly changed in the intervention group (P&lt;0.05), but no significant changes were seen in the control group (P&gt;0.05). Between-group differences respecting the post-test mean scores of these variables were also significant (P&lt;0.05). Conclusion: Thirty minutes of daily music therapy for 4 days is effective in reducing anxiety and depression and improving respiratory comfort among patients with COVID-19 under noninvasive mechanical ventilation.