Multicenter Clinical Trial Research Articles

Effect of Personalized Prebiotic and Probiotic Supplements on the Symptoms of Irritable Bowel Syndrome: An Open-Label, Single-Arm, Multicenter Clinical Trial.

Prebiotics and probiotics have been reported to improve symptoms of irritable bowel syndrome (IBS). Nevertheless, the effects of prebiotics/probiotics can vary depending on the IBS subtypes. The purpose of this study was to investigate the effects of personalized prebiotic and probiotic supplements based on intestinal microbiota and IBS subtypes in patients. Patients with diarrhea-type IBS (IBS-D), constipation-type IBS (IBS-C), and mixed-type IBS (IBS-M) were enrolled (n = 40 per group; total: n = 120). Personalized prebiotic and probiotic supplements were determined according to the IBS subtypes and intestinal microbiota. The patients received supplements for 4 weeks. The primary outcome was the change in the IBS-severity scoring system from baseline to week 4. The IBS-severity scoring system significantly decreased in all patients (-38.0 [95% confidence interval (CI): -53.6, -22.4]; p < 0.001), in patients with IBS-D (-44.5 [95% CI: -70.6, -18.5]; p = 0.004) and IBS-C (-51.2 [95% CI: -79.4, -22.9]; p = 0.002), but not in those with IBS-M (-20.0 [95% CI: -48.0, 8.1]; p = 0.47). In this study, no serious adverse events were observed that had a causal relationship with the intervention. In conclusion, personalized prebiotic and probiotic supplements selected according to individual intestinal microbiota and IBS subtype may alleviate the severity of IBS symptoms, particularly in patients with IBS-C and IBS-D.

Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

P1.06C.03 Prediction of STAS by Intraoperative Frozen Section for cT1N0M0 Lung Adenocarcinoma: A Prospective, Multi-Center Clinical Trial (ECTOP-1016)

P1.06C.03 Prediction of STAS by Intraoperative Frozen Section for cT1N0M0 Lung Adenocarcinoma: A Prospective, Multi-Center Clinical Trial (ECTOP-1016)

Test-retest and interrater reliability of experimental within-subject variability of pain reports as assessed by the focused analgesia selection test.

Within-subject variability (WSV) of pain intensity reports has been shown to predict the placebo response. The focused analgesia selection test (FAST), which allows to experimentally assess WSV of pain reports, has been used as a screening tool to identify participants who are likely to have a strong placebo response in drug-development clinical trials. Yet, the reliability of FAST has not been reported. To assess test-retest and interrater reliability of the FAST outcomes. To mimic pharma-sponsored clinical trials, we enlisted inexperienced assessors who underwent limited training. Healthy volunteers performed the FAST twice within a week and were randomly assigned to either the test-retest group or the interrater group. T-tests, partial Pearson correlations, intraclass correlations (ICC), and Bland-Altman plots were generated to assess FAST outcomes' reliability. Sixty-three participants completed the study and were assigned to the test-retest (N = 33) or interrater (N = 30) arms. No statistically significant differences in the FAST outcomes were detected between the 2 sessions, except for the FAST covariance (FAST CoV) in the interrater assessment (P = 0.009). Test-retest reliabilities of the FAST-main outcomes were r = 0.461, ICC = 0.385 for the FAST R 2 and r = 0.605, ICC = 0.539 for the FAST ICC and in the interrater cohort, they were FAST R 2: r = 0.321, ICC = 0.337 and FAST ICC: r = 0.355, ICC = 0.330. Using inexperienced assessors, the FAST outcomes test-retest ranged from moderate to strong, whereas the interrater reliability ranged from weak to poor. These results highlight the importance of adequately training study staff members before using this tool in multicentre clinical trials.

The impact of closed suction wound drainage on chronic pain and health-related quality of life after posterior spinal fusion in patients with adolescent idiopathic scoliosis.

Closed suction subfascial drainage is widely used after instrumented posterior spinal fusion in patients with a spinal deformity. The aim of this study was to determine the effect of this wound drainage on the outcomes in patients with adolescent idiopathic scoliosis (AIS). This was a further analysis of a randomized, multicentre clinical trial reporting on patients after posterior spinal fusion using segmental pedicle screw instrumentation. In this study the incidence of deep surgical site infection (SSI) and chronic postoperative pain at two years' follow-up are reported. We conducted a randomized, multicentre clinical trial on adolescents undergoing posterior spinal fusion for AIS using segmental pedicle screw instrumentation. A total of 90 consecutive patients were randomized into a 'drain' or 'no drain' group at the time of wound closure, using the sealed envelope technique (1:1). The primary outcomes in the initial study were the change in the level of haemoglobin in the blood postoperatively and total blood loss. A secondary outcome was the opioid consumption immediately after surgery. The aim of this further study was to report the rate of deep SSI and persistent postoperative pain, at two years' follow-up. As previously reported, the mean 48-hour opioid consumption was significantly higher in the no drain group (2.0 mg/kg (SD 0.8) vs 1.4 mg/kg (SD 0.7); p = 0.005). There were no delayed deep SSIs. At two years' follow-up, the mean Scoliosis Research Society 24-item questionnaire (SRS-24) total score did not differ between the groups (4.11 (SD 0.47) vs 4.16 (SD 0.33); p = 0.910). The mean SRS-24 pain score was 4.28 (SD 0.48) in the no drain group compared with 4.33 (SD 0.66) in the drain group (p = 0.245). Seven patients (19%) in the no drain group and six in the drain group (14%) reported moderate to severe pain (numerical rating scale ≥ 4) at two years' follow-up (p = 0.484). The general self-image domain score was significantly higher in the no drain group compared with the drain group (4.02 (SD 0.74) vs 4.59 (SD 0.54); p < 0.001). The main finding in this study was that more severe pain immediately after surgery did not result in a higher incidence of chronic pain in the no drain group compared with the drain group. Back pain and health-related quality of life at two years' follow-up did not differ between the groups. The patient-reported self-image domain was significantly better in the no drain group compared with the drain group.

Outcome and Risk of Poststroke Pneumonia in Patients with Acute Ischemic Stroke After Endovascular Thrombectomy: A Post Hoc Analysis of the DIRECT-MT Trial.

In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

Effects of mixed nuts as part of a Brazilian Cardioprotective diet on LDL-cholesterol in adult patients after myocardial infarction: a multicenter randomized controlled clinical trial

BackgroundNuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction.MethodsDICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality.ResultsAfter adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study.ConclusionAdding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting.Trial registrationThis study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259–8105.

Safety and efficacy of personalised versus standard dosing of linezolid in patients with sepsis (SePkLin): a pragmatic, multicentre, randomised, controlled and superiority clinical trial protocol.

Linezolid is a broadly used antibiotic to treat complicated infections caused by gram-positive bacteria. Therapeutic drug monitoring of linezolid concentrations is recommended to maximise its efficacy and safety, mainly haematological toxicity. Different pharmacokinetic/pharmacodynamic targets have been proposed to improve linezolid exposure: the ratio of the area under the concentration-time curve during a 24-hour period to minimum inhibitory concentration (MIC) between 80 and 120; percentage of time that the drug concentration remains above the MIC during a dosing interval greater than 85% and the trough concentration between 2 and 7 mg/L. This clinical trial aims to evaluate the safety, efficacy and the clinical and economic utility of personalised dosing of linezolid using Bayesian forecasting methods to attain pharmacokinetic/pharmacodynamic targets, known as model-informed precision dosing. This is a pragmatic, multicentre, randomised, parallel, controlled, phase IV and low intervention trial. Participants will be randomly assigned 1:1 to each group (n=346 per group). Control group will receive the standard dose of linezolid. Intervention group will receive personalised dosage of linezolid based on pharmacokinetic-pharmacodynamic adjustments. The primary outcome will be the incidence of thrombocytopenia in both groups. This protocol was approved by the Ethical Committee of the Investigation with Medicines of Galicia (code 2022/140) and authorised by the Spanish Agency for Medicines and Medical Devices. The trial is implemented in accordance with the Declaration of Helsinki and the international ethical and scientific quality standard, the Good Clinical Practice. The results will be published in peer-reviewed journals. EudraCT registration code: 2022-000144-30.

Racial representation in multicenter clinical trials leading to drug approvals for gynecological cancer indications by the US Food and Drug Administration (FDA).

66 Background: Enrollment disparities in gynecologic (Gyn) cancer clinical trials in the United States (US) are well-documented. However, there is limited data evaluating how recruitment sites in international clinical trials contribute to racial representation, specifically in Gyn cancers. Here, we examined racial enrollment and geographic location in clinical trials that have led to approval for Gyn cancer applications. Methods: Agents approved by the FDA for Gyn cancer treatment and corresponding clinical trials were identified from the FDA Drug Approvals and Databases. Enrollment data were abstracted from ClinicalTrials.gov then cross-checked with published manuscripts and FDA labels. Using Gyn disease site prevalence from the 2021 SEER database, we calculated expected enrollment proportions by race and compared these to actual clinical trial enrollment data. The binomial test was used to compare expected vs. observed proportions with White patients as the reference group. Results: From 2014 to 2024, 9 drugs received 22 FDA approvals for ovarian (n=13), endometrial (n=4), or cervical cancer (n=5). These approvals were based on 28 clinical trials enrolling a total of 13,763 patients (75.7% White, 3.4% Black, 12.0% Asian, 8.9% Other/Unknown). These trials included 1 (3.6%) US only study, 3 (10.7%) non-US, primarily Europe-based studies (PAOLA-1, AURELIA, STUDY42 [Europe + Australia]), and 24 (85.7%) international studies across the US and 46 other countries. Considering the distribution of race (White: 86.3%, Black: 8.4%, Asian: 4.9%) of Gyn cancers in the US, Black patients had lower enrollment (45% of expected enrollment) vs. White patients (95% of expected enrollment, P&lt;0.0001). African countries were rarely included among the recruitment sites. Two international trials reported patient recruitment from South Africa (3.2% Black, 6/188 patients, 38% of expected enrollment).However, Asian patients had higher enrollment (269% of expected enrollment, P&lt;0.0001) compared to White patients. In 13 trials that included study sites in East Asia, Asian patients comprised 16% of the trial population (1310/8205 patients; 327% of expected enrollment) vs. 3.2% in trials that did not open in Asia (n=15) (181/5558 patients; 67% of expected enrollment). Conclusions: Black patients were underrepresented in pivotal trials that led to FDA approvals for Gyn cancers. Overrepresentation of Asian patients was likely due to international enrollment from East Asia. Post-marketing retrospective studies or additional studies focused on underrepresented groups are needed to assess true drug efficacy and safety in US populations that are disproportionately affected by Gyn cancer mortality.

De Novo Atherosclerotic Renal Artery Stenosis Covered Stent Treatment for Resistant Hypertension (ARTISAN) Results

BackgroundAtherosclerotic renal artery stenosis (ARAS) may provoke hypertension and/or impaired kidney function. Some patients develop uncontrolled hypertension and deteriorating kidney function despite optimal medical therapy. In these patients, endovascular treatment is an important therapeutic option. ARTISAN was a prospective, open-label, single-arm, multicenter clinical trial to evaluate the safety and effectiveness of the iCast RX covered stent both functionally for reestablishing renal artery flow, and clinically for controlling resistant hypertension. MethodsPatients considered for enrollment had average systolic blood pressure (SBP) ≥155 mm Hg despite taking 3 antihypertensive medications. Prior to enrollment and covered stent placement, angiographic confirmation of ARAS ≥80% with physiologic significance was required. Clinical assessments were performed at 30 days, 9 months, and annually through 36 months. Covered stent safety and efficacy were based on 9-month coprimary end points, including primary vessel patency and SBP improvement at 9 months. Secondary outcomes included target lesion revascularization, major adverse events, and secondary patency. ResultsSixty-eight of the planned 138 subjects were enrolled. Primary patency was seen in 94.3% of subject lesions; the mean SBP reduction was 15.7 mm Hg. The functional and clinical end points met prespecified performance goals of 70% primary patency (P < .0001) and ≥10 mm Hg SBP decrease (P = .0192), respectively, at 9 months. Six subjects (8.8%) experienced 7 major adverse events within 36 months. The clinically driven target lesion revascularization rate was 7.3% at 36 months. ConclusionsThe high primary patency and improvement in SBP, persisting through 36 months, suggest that the iCast RX covered stent is safe and effective for the treatment of appropriately selected patients with ARAS.

Non-pharmacological interventions of traditional Chinese medicine in treating polycystic ovary syndrome: a group consensus

ObjectiveTo make a group consensus about non-pharmacological interventions of traditional Chinese medicine in treating polycystic ovary syndrome based on the previous guidelines, literature, and expert viewpoints. MethodsOrganized by Chinese Integrative Medicine & Traditional Chinese Medicine Academy, Chinese Maternal and Child Health Association, China, 29 experts from 18 Chinese provinces and 2 international experts, who specialize in gynecology, obstetrics, pediatrics, endocrinology, cardiovascular, psychology, reproductive genetics, nursing, acupuncture and tuina, traditional Chinese medicine, integrative medicine, and other disciplines, discussed and revised the recommendations one by one through in-person or online communication. Each recommendation was approved by ≥90% of the experts before it could be established. Main outcome measure(s)An optimal clinical regimen for addressing the requirements of women with PCOS and improving their quality of life. Result(s)The writing panel drafted the initial report, following a consensus process via adequate communication, which was then reviewed and revised by the consensus panel. This consensus provides 12 non-pharmacological interventions (including acupuncture, thumbtack needle, thread-embedding therapy, TEAS, AA, acupoint hot compress, cupping, acupressure, moxibustion, five elements music, aromatherapy, traditional Chinese exercises) for 8 phenotypes of PCOS, resulting in 34 items of clinical practice recommendations. Conclusion(s)The consensus provides 12 non-pharmacological interventions of traditional Chinese medicine for 8 phenotypes of PCOS, resulting in 34 items of clinical practice recommendations, which may be improved by more high-quality multicenter clinical trials.

History of tobacco smoking and alcohol use can predict the effectiveness of electroconvulsive therapy in individuals with schizophrenia: A multicenter clinical trial

BackgroundCurrent research has found that factors such as gender, age, and family history can predict the efficacy of electroconvulsive therapy (ECT) in individuals with schizophrenia. In our clinical practice, we anecdotally observed that tobacco smokers and alcohol drinkers with schizophrenia seemed to respond more effectively to ECT than non-smokers and non-drinkers. The current study aimed to examine whether history of tobacco smoking or alcohol consumption serve as indicators for predicting therapeutic efficacy of ECT in individuals with schizophrenia. MethodsA total of 481 individuals receiving ECT combined with antipsychotic medication (ECT + AP medication) completed a two-week (six sessions of ECT) follow-up; 106 individuals receiving only antipsychotic medication (AP medication) also completed a two-week follow-up. Smoking, alcohol consumption, and AP medication usage was recorded for these individuals. Severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). ResultsECT + AP medication: Compared to schizophrenic individuals without a history of smoking (non-smokers), those with a history of smoking (smokers) showed a high decrease in negative symptoms (36.96% vs 24.76%; F = 5.974, p = 0.015). While, compared to individuals without a history of alcohol consumption (non-drinkers), those with a history of alcohol consumption (drinkers) showed a high decrease in positive symptoms (48.90% vs 41.47%; F = 5.074, p = 0.025). AP medication: No differences were found in symptom reduction between smokers and non-smokers or between drinkers and non-drinkers (p > 0.05). ConclusionsSmoking history in schizophrenic individuals independently predicts better improvement in negative symptoms after ECT, while alcohol consumption history independently predicts better improvement in positive symptoms after ECT. This is a clinically significant finding.

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

Protocol for a feasibility multi-centre randomised controlled trial of a pre-operative two-week very low-calorie diet to reduce steatosis prior to liver resection (RESOLVE)

BackgroundHepatic steatosis (HS) increases morbidity and mortality associated with liver surgery (LS). Furthermore, patients with HS are more likely to require a blood transfusion, which is associated with worse short and long-term outcomes. Patients with HS requiring LS receive no specific dietary treatment or advice. A very low-calorie diet (VLCD) is commonly used before gallbladder and bariatric surgery to reduce liver volumes and associated intraoperative morbidity. These diets typically provide 800–1200 kcal/day over a 2–4-week period. Limited evidence suggests that a VLCD in patients with LS may result in better outcomes.MethodsThis study aims to test the feasibility of delivering a multi-centre randomised clinical trial to compare a dietary intervention (VLCD plus motivational instructions) versus treatment as usual (TAU) in people with HS having LS. This study will provide high-quality data to estimate screening rates, recruitment, randomisation, retention, and intervention adherence. The study will also determine the definitive trial’s most clinically relevant primary outcome. The study will also estimate resource use and costs associated with the delivery of the intervention. Seventy-two adults ≥ 18 who are scheduled to undergo elective LS and have a magnetic resonance imaging (MRI) identified HS will be recruited. Acceptability to the dietary intervention will be evaluated with food diaries and focus groups. Clinical and patient-reported outcomes will be collected at baseline, pre- and post-surgery, day of discharge, plus 30- and 90-day follow-up.DiscussionThis feasibility study will provide data on the acceptability and feasibility of a dietary intervention for patients with HS having LS. The intervention has been developed based on scientific evidence from other clinical areas and patient experience; therefore, it is safe for this patient group. Patients with experience of LS and VLCDs have advised throughout the development of the study protocol. The findings will inform the design of a future definitive study.Trial registrationISRCTN Number 19701345. Date registered: 20/03/2023. URL: https://www.isrctn.com/ISRCTN19701345.

Efficacy and safety of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause: A randomized double-blind placebo-controlled trial

ObjectivesThis study evaluated the efficacy of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause. Study designRandomized, double-blind, placebo-controlled, multicenter clinical trial conducted across 28 Spanish sites involving specialists in gynecology, urology, and primary care. A total of 108 postmenopausal women were randomly assigned in a 1:1 ratio to receive 1 g of vaginal gel with 50 micrograms of estriol or an identical moisturizing vaginal gel without estriol. Main outcome measuresThe primary outcome was the number of episodes of urinary tract infection by the end of the 24-week treatment. Secondary measures encompassed percentage of patients without recurrence, time to first recurrence, use of antibiotic treatment, vaginal pH, safety, and tolerability, among others. ResultsThe incidence rate of urinary tract infections (new cases per 100 women-year) was 26 % lower in the group that received estriol vs. the group that received placebo (32.34 vs. 43.76 (RR = 0.74) p < 0.001). The frequency of urinary tract infections fell during treatment in all patients in the estriol group. Favorable pH changes from baseline were observed in the estriol arm at all follow-up visits. ConclusionsUltra-low-dose 0.005 % estriol vaginal gel is safe and effective in preventing recurrent urinary tract infections in postmenopausal women with genitourinary syndrome of menopause, reducing the incidence and potentially decreasing the susceptibility to urogenital infections by improving vaginal pH.Study registration N°: 2018-001481-42. Date of registration: 09-04-2018.

Cost-effectiveness of MLC601 in post-stroke functional recovery compared with placebo - the CHIMES & CHIMES-E studies

BackgroundDespite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14).MethodsA Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs.ResultsBase-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust.ConclusionCompared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study.Trial registrationURL http://www.clinicaltrials.gov. Unique identifier NCT00554723 November 7, 2007.

From pain level to pain experience: redefining acute pain assessment to enhance understanding of chronic postsurgical pain

BackgroundChronic postsurgical pain (CPSP) significantly impairs quality of life and poses a substantial healthcare burden, affecting up to a quarter of patients undergoing surgery. Although acute pain is recognised as a predictor for CPSP development, the role of patient experience remains underexplored. This study examines the predictive value of patient experience alongside traditional risk factors for CPSP after orthopaedic surgery. MethodsAn exploratory analysis was conducted on 294 patients from a multicentre randomised clinical trial comparing continuous perineural analgesia and single-injection nerve block in ambulatory orthopaedic surgeries. Patient experience was assessed using the Evaluation du Vecu de l’Anesthésie Générale (EVAN-G) validated questionnaire. Factors associated with CPSP at 90 days after surgery were identified through univariate and multivariate analyses, incorporating patient-reported outcomes and classical variables. ResultsOut of 219 patients with complete data, 63 (29%) developed CPSP at day 90. Multivariate analysis revealed a poor pain experience, as assessed by the pain dimension of EVAN-G on postoperative day 2, as an independent predictor of CPSP (odds ratio 6.45, 95% confidence interval 1.65–25.26, P<0.01). Poor pain experience was associated with an augmented risk of CPSP. ConclusionsThis study underscores the role of patient-reported outcomes, specifically the pain experience dimension captured by the EVAN-G scale, in prediction of CPSP 90 days after surgery. It suggests a shift from conventional assessments of pain intensity to a comprehensive understanding of pain experience, advocating for tailored pain management approaches that could reduce chronic pain, thereby improving patient quality of life and functional recovery.

Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates

A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes. To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units. This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024. Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up. The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA. A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups. In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Comparative postoperative prognosis of ceramic-on-ceramic and ceramic-on-polyethylene for total hip arthroplasty: an updated systematic review and meta-analysis.

To compare the clinical outcomes between ceramic-on-ceramic (CoC) and ceramic-on-polyethylene (CoP) bearing surfaces in patients undergoing total hip arthroplasty (THA) through a pooled analysis and evidence update. We performed a systematic literature search using PubMed, Embase, Cochrane Library and Web of Science up to March 2023 for studies that compared the bearing surfaces of CoC and CoP in patients undergoing THA. The primary outcomes were the incidence of common postoperative complications and the rate of postoperative revision. The secondary outcome was the Harris Hip Score. A total of 10 eligible studies involving 1,946 patients (1.192 CoC-THA versus 906 CoP-THA) were included in the evidence synthesis. Pooled analysis showed no significant difference in the rates of common postoperative complications (dislocation, deep vein thrombosis, infection, wear debris or osteolysis) and of revision. After eliminating heterogeneity, the postoperative Harris Hip Score was higher in the CoC group than in the CoP group. However, the strength of evidence was moderate for the Harris Hip Score. CoC articulations are more commonly used in younger, healthier, and more active patients. While the performance of conventional polyethylene is indeed inferior to highly cross-linked polyethylene, there is currently a lack of sufficient research comparing the outcomes between highly cross-linked polyethylene and CoC bearing surfaces. This area should be a focal point for future research, and it is hoped that more relevant articles will emerge. Given the limited number of studies included, the heterogeneity and potential bias of those included in the analysis, orthopaedic surgeons should select a THA material based on their experience and patient-specific factors, and large multicentre clinical trials with >15 years of follow-up are needed to provide more evidence on the optimal bearing surface for initial THA.

Evaluating the Effect of a Novel Digital Ostomy Device on Leakage Incidents, Quality of Life, Mental Well-Being, and Patient Self-Care: An Interventional, Multicentre Clinical Trial

Background: Most people with a stoma worry about leakage, and a quarter experience leakage of stomal effluent outside the baseplate on a monthly basis. Leakage has additional physical and psychosocial consequences, for instance, peristomal skin complications, feeling unable to cope, and self-isolation. Method: An interventional, single-arm, multi-centre study was undertaken in the United Kingdom to evaluate a novel digital leakage notification system for ostomy care, including a support service (=test product) for 12 weeks in patients with a recent stoma formation (≤9 months). Patients completed questionnaires at baseline and after 4, 6, 8, 10, and 12 weeks, evaluating leakage episodes, Ostomy Leak Impact (tool containing three domains), and patient self-management (by PAM-13). Additionally, mental well-being (by WHO-5) and health-related quality of life (QoL) (by EQ-5D-5L) were assessed. Outcomes between baseline and final evaluation were compared by generalised linear and linear mixed models. Results: 92 patients (ITT population) with a mean age of 49.4 years (range 18–81 years) were recruited. Of these, 80% had an ileostomy, and 53% were female. After 12 weeks of using the test product, a significant decrease in mean episodes of leakage outside the baseplate (1.57 versus 0.93, p &lt; 0.046) was observed. Ostomy Leak Impact scores improved across all three domains (p &lt; 0.001), indicating less embarrassment, increased engagement in social activities, and increased control. Patient self-management also improved significantly (PAM-13 score: ∆6.6, p &lt; 0.001), as did the WHO-5 well-being index (∆8.0, p &lt; 0.001). Lastly, EQ-5D-5L profile scores tended to improve (p = 0.075). Conclusions: A new digital leakage notification system demonstrated strong improvements to patients’ stoma self-care, mental well-being, and QoL. Registration number on ClinicalTrials.gov: NCT05135754.