Non-randomized Controlled Trials Research Articles

Adenotonsillectomy Versus Watchful Waiting for Children with Obstructive Sleep Apnea Syndrome: A Systematic Review with Meta-Analysis

AbstractThe treatment of children with Obstructive Sleep Apnea Syndrome (OSAS) remains a point of debate among otorhinolaryngologists worldwide. This study aims to comparatively assess the clinical outcomes of adenotonsillectomy (ATE) and watchful waiting in children with OSAS. We searched the databases of PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), until the 1st of October 2023. Comparative trials assessing the efficacy of adenotonsillectomy and watchful waiting in children with OSAS were considered. The primary outcome measure was the apnea-hypopnea index (AHI), and secondary outcomes included quality of life as measured by OSA-18 score, and mean SpO2 levels. A subgroup analysis evaluating the changes in AHI depending on the severity of the initial disease was also executed. We conducted a random-effects pairwise meta-analysis of change scores to include randomized and non-randomized controlled trials. The quality assessment was carried out by using the Cochrane risk of bias tool for randomized and the ROBINS-I tool for non-randomized trials, respectively. Two randomized and five non-randomized trials were included. There was a statistically significant difference regarding AHI in favor of the ATE group compared to the watchful waiting group (Standardized mean difference [SMD] was − 0.60, 95%CI −0.79 to −0.41, p < 0.001). Likewise, a statistically significant decrease in change scores for OSA-18 between ATE and watchful waiting was noted (SMD was − 0.79, 95%CI −0.97 to −0.61, p < 0.001). On the other hand, there was no significant difference when ATE and watchful waiting groups were compared for SpO2 levels between each other (SMD was 0.52, 95%CI −1.53 to 2.56, p < 0.62). In the subgroup analysis assessing mild OSAS, there was a significant difference in favor of ATE compared to watchful waiting (SMD was −0.91, 95%CI −1.35 to −0.47, p < 0.0001). For mild to moderate OSAS, similar results were noted favoring ATE as well (SMD was − 0.53, 95%CI −0.87 to −0.19, p < 0.003). This study provides evidence of moderate strength supporting the superiority of ATE over the watchful waiting approach in terms of AHI and OSA-18. This also appears to be the case for AHI in children with mild and mild to moderate OSAS.

Effectiveness of implementation strategies for increasing clinicians' use of five validated imaging decision rules for musculoskeletal injuries: a systematic review.

Strategies to enhance clinicians' adherence to validated imaging decision rules and increase the appropriateness of imaging remain unclear. To evaluate the effectiveness of various implementation strategies for increasing clinicians' use of five validated imaging decision rules (Ottawa Ankle Rules, Ottawa Knee Rule, Canadian C-Spine Rule, National Emergency X-Radiography Utilization Study and Canadian Computed Tomography Head Rule). Systematic review. The inclusion criteria were experimental, quasi-experimental study designs comprising randomised controlled trials (RCTs), non-randomised controlled trials, and single-arm trials (i.e. prospective observational studies) of implementation interventions in any care setting. The search encompassed electronic databases up to March 11, 2024, including MEDLINE (via Ovid), CINAHL (via EBSCO), EMBASE (via Ovid), Cochrane CENTRAL, Web of Science, and Scopus. Two reviewers assessed the risk of bias of studies independently using the Cochrane Effective Practice and Organization of Care Group (EPOC) risk of bias tool. The primary outcome was clinicians' use of decision rules. Secondary outcomes included imaging use (indicated, non-indicated and overall) and knowledge of the rules. We included 22 studies (5-RCTs, 1-non-RCT and 16-single-arm trials), conducted in emergency care settings in six countries (USA, Canada, UK, Australia, Ireland and France). One RCT suggested that reminders may be effective at increasing clinicians' use of Ottawa Ankle Rules but may also increase the use of ankle radiography. Two RCTs that combined multiple intervention strategies showed mixed results for ankle imaging and head CT use. One combining educational meetings and materials on Ottawa Ankle Rules reduced ankle injury imaging among ED physicians, while another, with similar efforts plus clinical practice guidelines and reminders for the Canadian CT Head Rule, increased CT imaging for head injuries. For knowledge, one RCT suggested that distributing guidelines had a limited short-term impact but improved clinicians' long-term knowledge of the Ottawa Ankle Rules. Interventions such as pop-up reminders, educational meetings, and posters may improve adherence to the Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian CT Head Rule. Reminders may reduce non-indicated imaging for knee and ankle injuries. The uncertain quality of evidence indicates the need for well-conducted RCTs to establish effectiveness of implementation strategies.

The Impact of Exercise Training on Muscle Sympathetic Nerve Activity: A Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to examine the effects of exercise training on muscle sympathetic nerve activity (MSNA) in humans. Studies included exercise interventions (randomized controlled trials [RCTs], non-randomized controlled trials [non-RCTs] or pre-to-post intervention) that reported on adults (>18 years) where MSNA was directly assessed using microneurography, and relevant outcomes were assessed (MSNA [total activity, burst frequency, burst incidence, amplitude], heart rate, blood pressure [systolic blood pressure, diastolic blood pressure, or mean blood pressure], and aerobic capacity [maximal or peak oxygen consumption]). 40 intervention studies (n=1,253 individuals) were included. RCTs of exercise compared to no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared to controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared to those without. However, the reduction in burst incidence was greater in those with cardiovascular disease (9 RCTs studies, n = 234, MD -21.08 bursts/100 hbs; 95% CI -16.51, -25.66; I2 = 63%) compared to those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence pre-intervention had a greater reduction in values post-intervention. These findings suggest that exercise training reduces muscle sympathetic nerve activity, which may be valuable for improving cardiovascular health.

Impact evaluation of a cash-plus programme for children with disabilities in the Xiengkhouang Province in Lao PDR: study protocol for a non-randomised controlled trial

IntroductionMore than 170 countries have implemented disability-targeted social protection programmes, although few have been rigorously evaluated. Consequently, a non-randomised controlled trial is being conducted of a pilot ‘cash-plus’ programme implemented...

Outcome comparison of meniscal allograft transplantation (MAT) and meniscal scaffold implantation (MSI): A systematic review.

Although numerous studies have reported successful clinical outcomes of Meniscal allograft transplantation (MAT) or Meniscal scaffold implantation (MSI), the difference between the outcome of MAT and MSI remains unclear. To compare the overall outcomes and survival rates of MAT and MSI, aiming to provide comprehensive evidence for determining the optimal treatment strategy for meniscal defects. A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of MAT or MSI were included according to the inclusion and exclusion criteria. The Lysholm score was chosen as the primary outcome measure, while secondary outcomes encompassed Patient-reported Outcome Measures (PROMs), Return to Sports (RTS) rates, survival rates, and complication rates. The outcomes were stratified into two groups: MAT group and MSI group, followed by statistical comparison (P<0.05). The quality of the included studies was assessed by the Cochrane Risk of Bias 2 (RoB2) assessment tool for randomized controlled trials (RCTs) and the Coleman Methodology Score (CMS) for non-randomized controlled trials. A total of 3932 patients (2859 MAT, 1073 MSI) in 83 studies (51 MAT, 32 MSI) had the overall significant improvement in all clinical scores. The group MSI had higher Lysholm score of both preoperative (P=0.002) and postoperative (P<0.001) than group MAT; however, the mean improvements were similar between the two groups (P=0.105). Additionally, MSI had higher improvements of IKDC (P<0.001), KOOS symptom (P=0.010), KOOS pain (P=0.036), and KOOS ADL (P=0.004) than MAT. Interestingly, MAT had higher preoperative (P=0.018) and less postoperative VAS pain (P=0.006), which was more improved in MAT (P<0.001). Compared with MAT, MSI had higher 10-year survival rate (P=0.034), similar mid-term survival rate MAT (P=0.964), and lower complication rate (P<0.001). Both MAT and MSI could have good clinical outcomes after surgery with the similar improvement in Lysholm score. MSI had higher 10-year survival rate and less complications than MAT. IV, systematic review.

SupporTive Care At Home Research (STAHR) for patients with advanced cancer: Protocol for a cluster non-randomized controlled trial.

Advancements in the treatment and management of patients with cancer have extended their survival period. To honor such patients' desire to live in their own homes, home-based supportive care programs have become an important medical practice. This study aims to investigate the effects of a multidimensional and integrated home-based supportive care program on patients with advanced cancer. SupporTive Care At Home Research is a cluster non-randomized controlled trial for patients with advanced cancer. This study tests the effects of the home-based supportive care program we developed versus standard oncology care. The home-based supportive care program is based on a specialized home-based medical team approach that includes (1) initial assessment and education for patients and their family caregivers, (2) home visits by nurses, (3) biweekly regular check-ups/evaluation and management, (4) telephone communication via a daytime access line, and (5) monthly multidisciplinary team meetings. The primary outcome measure is unplanned hospitalization within 6 months following enrollment. Healthcare service use; quality of life; pain and symptom control; emotional status; satisfaction with services; end-of-life care; advance planning; family caregivers' quality of life, care burden, and preparedness for caregiving; and medical expenses will be surveyed. We plan to recruit a total of 396 patients with advanced cancer from six institutions. Patients recruited from three institutions will constitute the intervention group, whereas those recruited from the other three institutions will comprise the control group.

Preliminary clinical observation and analysis of structural changes of optic nerve head in glaucoma patients after visual training

Objective: To investigate the effect of virtual reality visual training on remodeling optic nerve structures of glaucoma patients and analyze the influencing factors of visual training effect. Methods: A prospective non-randomized controlled trial was conducted. Glaucoma patients who presented to the Department of Ophthalmology, Beijing Shijitan Hospital between October 2021 and October 2022 were collected and divided into the training group or the control group according to their intentions. The training group accepted 3 months of visual training, while the control group did not. Optical coherence tomography was used to examine the disc edge area, cup volume, disc area, cup-to-disc ratio, and other parameters of the optic disc of both eyes of the patients at enrollment and after 3 months, and the changes of each parameter in the two groups were analyzed. Multivariate analysis was performed in the training group to investigate the effects of sex, age, visual field index, and mean defect on visual disc structure changes during visual training. Results: A total of 53 glaucoma patients (101 eyes) were included in the final analysis, among which the training group consisted of 27 cases (51 eyes), with 19 males and 8 females, and the age range was 48.0 (40.0, 61.0) years old. The control group comprised 26 cases (50 eyes), with 26 males and 11 females, and the age range was 54.0 (38.0, 63.0) years old. Compared with the control group, the deviation of cup volume was -0.006(-0.050, 0.015)mm3 (P<0.05), and the deviation of disc edge area was 0.00(-0.04, 0.05)mm2 (P<0. 05)in the visual training group after 3 months of visual training. The gender (OR=4.217, 95%CI=1.188-14.966) may be the influence factor of rim area. While,the mean defect (OR=1.526, 95%CI=0.245-9.491) was not that influential on rim area change. Conclusions: Visual training can increase the disc area and decrease the optic cup volume of the optic nerve in glaucoma patients. The rim area may be increased more easily after visual training in male glaucoma patients.

Effect of a higher protein diet and lifestyle camp intervention on childhood obesity (The COPE study): results from a nonrandomized controlled trail with 52-weeks follow-up

Abstract Purpose In adults, diets rich in protein seem beneficial in relation to satiety, weight loss, and weight management; however, studies investigating dietary protein and weight development in children are scarce and inconsistent. This nonrandomized controlled trial aimed to investigate the effect of a higher protein diet during lifestyle intervention on anthropometry and metabolic biomarkers in children with overweight and obesity. Methods Children (n:208) were recruited from two multicomponent lifestyle camps. One camp was assigned as the intervention group. In the intervention group, carbohydrates-rich foods at breakfast and two in-between-meals were replaced with protein-containing foods to increase the amount of protein from ~ 10–15 energy percent (E%) per day to ~ 25E% per day. Other components were similar between groups. Anthropometry and biochemical measurements were collected at baseline, 10 weeks (after camp) and 52 weeks. Results The intervention group had a non-significant improvement in BMI-SDS (− 0.07 SD (− 0.19; 0.05), p = 0.24) compared to the control group, but in general, there was no effect of a higher protein diet on anthropometry and metabolic biomarkers. Overall, 10 weeks at camp resulted in a more favorable body composition [− 6.50 kg (p &lt; 0.00), − 0.58 BMI-SDS (p &lt; 0.00), and − 5.92% body fat (p &lt; 0.00)], and improved metabolic health, with most changes maintained at 52 weeks. Conclusion A higher protein diet had no significant effect on body composition and metabolic health; however, these lifestyle camps are an efficiatious treatment strategy for childhood obesity. Clinical trial registration: clinicaltrials.gov with ID: NCT04522921. Preregistered August 21st 2020.

Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis

BackgroundRe-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery.MethodsA systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed.ResultsThirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort.ConclusionsIn post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

Comparison of Effects of Preserved and Preservative Free Anti-Glaucoma Drugs in Causing Dry Eyes

Objective: The aim of this study was to assess the potential impact of antiglaucoma medication preservatives on ocular surface health and the subsequent development of dry eye symptoms. Methods: A non-randomized controlled trial study was conducted from March 2023 to June 2023.The study enrolled 32 patients, with 16 participants in each group. Patients meeting the inclusion criteria, including confirmed diagnosis of glaucoma and stable ocular health, were allocated to Group A(preserved medication) or Group B(preservative-free medication).Tear Film Break-Up Time(TBUT) and Schirmer's test were employed as objective indicators of tear film stability and tear production respectively. Measurements were recorded at baseline and after a 3-month duration of medication use. Results: At 1st visit, mean TBUT was 10.87 sec and mean Schirmer's test was 13.75 mm in group A while in group B it was 11.25 sec and 14.56 mm respectively. After 3 months of medication use, mean TBUT and mean Schirmer’s was 9.62 sec and 11.81 mm respectively in group A while in group B it was 10.18 sec and 13.18 mm respectively. The results showed that initial ocular status was similar in both groups however the decrease in values showed ocular surface deterioration. Notably group A demonstrated a more substantial decline in tear production compared to group B. Conclusion: This study underscores the importance of both preserved and preservative-free anti-glaucoma medications. Although both may potentially exacerbate dry eye symptoms to a greater extent, preservative-free anti-glaucoma may offer benefits in maintaining ocular surface health with long-term use.

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review.

Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

Abstract PO2-01-04: Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis

Abstract Background: Human epidermal growth factor receptor-2 overexpression or gene amplification (HER2+) breast cancer is considered to be a highly aggressive, dangerous and even fatal subtype..In recent years, with the application of large molecule anti-HER2 monoclonal antibody and its biosimilar in neoadjuvant therapy of HER2-positive breast cancer, small molecule tyrosine kinase inhibitors (TKIs) have also performed strong advantages of antineoplastic activity in breast cancer. At present, there is no direct evidence to demonstrate the differences in neoadjuvant efficacy of anti-HER2 monoclonal antibody and tyrosine kinase inhibitors (TKIs) in this subtype of breast cancer.We conducted a preliminary network meta-analysis to explore the difference of efficacy and safety between anti-HER2 monoclonal antibody and TKIs for neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer. Method: A systematic literature search in the Cochrane Central Register of Controlled Trials, PubMed, Embase and Web of Science was performed.Randomized or non-randomized controlled studies of neoadjuvant therapy for HER2-positive breast cancer including large molecules trastuzumab, pertuzumab and small molecules TKIs (pyrotinib, lapatinib, nenatinib, etc.) were screened.Studies had to satisfy the following criteria: i) randomized or non-randomized controlled trials, ii) at least one treatment group received an anti-HER2 agent, iii) available information of any efficacy end-point. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR) were the efficacy end-points of interest, and selected safety end-points were also analysed. Results: A total of 5885 published manuscripts were identified,and 19 studies including 6517 patients were finally included in our analysis. and 19 different regimens were evaluated. Dual anti-HER2-therapy,trastuzumab with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab or TKIs and chemotherapy in terms of pCR(OR=2.20, 95%CI=1.92-2.52).In the comparison of dual-target treatment regiments, the efficacy of pyrotinib plus trastuzumab combined chemotherapy was superior to that of pertuzumab plus trastuzumab combined chemotherapy (OR=1.20, 95%CI=0.85-1.70), but the difference was not statistically significant.In addition, compared with pertuzumab combined with trastuzumab and chemotherapy,there was no significant difference in the efficacy aspect of TKIs combined with trastuzumab and chemotherapy (OR=1.15, 95%CI=0.88-1.51). Conclusion:For the selection of neoadjuvant treatment for HER2-positive early or locally advanced breast cancer, trastuzumab plus pertuzumab combined with chemotherapy is still the preferred strategy at present.As our study showed that pyrotinib combined with trastuzumab and chemotherapy maybe could provide another option for neoadjuvant target therapy for HER2-positive breast cancer. Keywords: breast cancer, HER2-positive, neoadjuvant, network meta-analysis, target therapy. Characteristics of eligible studies. NAC=Neoadjuvant chemotherapy;T=nab-paclitaxel,paclitaxel or Docetaxel;F= fluorouracil;E=epirubicin;A=doxorubicin;C=cyclophosphamide; Cb=carboplatin;tzmb=trastuzumb;pzmb=pertuzumab;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% CIs for pCR among different experimental arms. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% confidence intervals (CIs) for pathologic complete response (pCR) in HR-positive and HR-negative subgroups. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Citation Format: Lu Gan, Fangxuan Li, Jialin Su. Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-04.

A Systematic Review of Loco-Sedative Anesthesia for Urologic Surgery

ObjectiveTo perform a systematic review of the characteristics and outcomes of conscious sedation and local anesthesia for various urologic procedures. Urologic care has much to gain from the routine integration of ambulatory surgery via loco-sedative anesthetic techniques for both surgeon and patient. MethodsA comprehensive systematic literature search was conducted on PubMed, and Scopus databases following PRISMA criteria from June to August 2021. Articles were included if they were English, prospective, randomized, or non-randomized controlled trials that used local anesthetic or conscious sedation for urologic interventions in adult patients. Additionally, included studies provided primary data on the use loco-sedative anesthesia and the efficacy and complications. All studies included were further reviewed to assess the biases and conflicts of interests. Results32 studies with 6897 patients were included in the review. Mean patient age was 46.4 years. The most common anesthetic and analgesic relief was the use of local anesthetic with 1% lidocaine. The majority used lidocaine as an injection, whereas the second most common route of administration was a topical cream. However, there was significant heterogeneity in the type of local or conscious sedation method and whether a combination was used. 44.4% of the studies used the visual analog scale as their primary endpoint. All the studies reported an 83% to 100% successful procedure rate without note of significant sedation-related complications. ConclusionsGiven the high efficacy rates, loco-sedative anesthesia is a promising technique for urologic interventions and should be further investigated to determine whether it may become be the standard of care.

Effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine for postoperative analgesia in women undergoing cesarean section: a systematic review protocol.

The aim of this review is to compare the effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine in providing postoperative analgesia in patients undergoing cesarean section. Pain following cesarean section remains a challenge, with limited treatment options due to potential undesirable parturient and neonatal side effects. Intrathecal dexmedetomidine has emerged as a favorable alternative to opioid additives to hyperbaric bupivacaine in prolonging postoperative analgesia, but its effectiveness requires further investigation. The review will evaluate studies of patients who underwent cesarean section under spinal anesthesia where dexmedetomidine and fentanyl were compared as intrathecal additives to hyperbaric bupivacaine for postoperative analgesia. This review will consider randomized controlled trials, non-randomized controlled trials, and prospective cohort studies for inclusion. No limits regarding publication date or language will be applied. A preliminary search of PubMed and Cochrane Central Register of Controlled Trials has been conducted to identify relevant index terms and keywords, which will be applied in a second search across PubMed, Cochrane CENTRAL, Scopus, and Embase. Google Scholar, National Library of Medicine (Clinicaltrials.gov), and the World Health Organization International Clinical Trial Registry Platform will be searched to identify unpublished literature. Full-text studies will be subjected to an assessment of methodological quality, and data extraction will be performed independently by 2 reviewers. The results will be presented in both tabular and narrative format and, where possible, pooled into a meta-analysis. A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be created to grade the certainty of evidence of the reported outcomes. PROSPERO CRD42022364815.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Implications of Pimavanserin in Patients with Dementia-related Psychosis: A Systematic Review

Abstract Psychosis in patients with dementia-related disorders has long been a challenging issue to be tackled by the medical fraternity. Although atypical antipsychotics (AP) are in use for the same reason, there has always been a question regarding their safety and tolerability in this group of patients. Pimavanserin, a serotonin receptor inverse agonist or antagonist, is the only drug that is Food and Drug Administration-licensed to be used for the treatment of Parkinson's disease psychosis. This systematic review, which was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020, had the objective of examining the effects of pimavanserin in patients with dementia-related psychosis (DRP). Among the publications (January 1, 2013–July 12, 2023) we gathered and examined were case–control and cohort studies, systematic reviews, meta-analyses, clinical trials, literature reviews, and randomized and nonrandomized control trials. The databases used to construct this list of publications were PubMed, Cochrane Library, and Google Scholar. These three databases yielded 157 reports in total once the relevant filters were applied. They were then further screened and put through quality evaluation processes, which led to the final nine papers that were included in this systematic review. We concluded from our review that pimavanserin proves to be a promising alternative for the treatment of DRP, showing significant improvements and fewer side effects compared to other atypical AP.

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer

Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. ClinicalTrials.gov Identifier: NCT03239613.

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials

ABSTRACT Objectives: Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Materials and Methods: Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Results: Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1–2 relapses (MD = 0.44, [95% CI: 0.21–0.91]) and had higher eGFR values (MD = 6.67; [CI − 2.92–10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Conclusion: Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.

Effects of intermittent fasting on periodontal inflammation and subgingival microbiota.

Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota. This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n=14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing. After 6months of intermittent fasting, weight, body mass index, C-reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p<0.05). Moreover, significant reductions were observed in bleeding on probing (p=0.01) and the presence of shallow periodontal pockets after fasting (p<0.001), while no significant change was seen in plaque index (p=0.14). While we did not observe significant changes in α- or β-diversity of the subgingival microbiota related to dietary intervention (p>0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4-5mm compared to those with <60% reduction (bad responders). Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea

Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. 140 mg of erenumab every 4 weeks for 12 weeks. The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by -6.9 days (95% CI, -10.4 to -3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by -8.1 days (95% CI, -12.5 to -3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. ClinicalTrials.gov Identifier: NCT04419259.