Incidence Of Other Adverse Events Research Articles

Ciprofol versus propofol for anesthesia induction in cardiac surgery: a randomized double-blind controlled clinical trial.

Ciprofol, a novel intravenous general anesthetic with a chemical structure similar to propofol, exhibits significantly enhanced potency. It offers a rapid onset, reduced incidence of injection pain, and has comparable effects on heart rate and blood pressure to propofol. However, clinical data on its use for anesthesia induction in cardiac surgery remain limited. Seventy-eight patients undergoing coronary artery bypass grafting or valve replacement surgery were randomly assigned to receive either ciprofol (N = 40) or propofol (N = 38) for anesthesia induction. Variables recorded included changes in mean arterial pressure and heart rate during anesthesia, alterations in the oxygenation index and lactic acid concentration before and 10min after anesthesia induction, and the incidence of adverse events such as bradycardia, hypotension, and injection pain. The incidence of anesthesia-induced injection pain was significantly lower in the ciprofol group compared to the propofol group (3% vs. 18%, P < 0.05). The incidence of other adverse events was similar between the groups. No significant differences in hemodynamics or oxygenation index were observed during anesthesia induction between ciprofol and propofol. Ciprofol demonstrated a significantly lower incidence of injection pain compared to propofol, potentially improving patient comfort during anesthesia induction. Additionally, ciprofol showed comparable circulatory stability to propofol during anesthesia induction in cardiac surgery, suggesting it may be a suitable alternative to propofol for this application. The trial was registered at the ClinicalTrials.gov on 03/10/2024 (NCT06312345).

Treating acid reflux without compressing the food passageway: 4-year safety and clinical outcomes with the RefluxStop device in a prospective multicenter study

IntroductionRefluxStop is an implantable device for laparoscopic surgical treatment of gastroesophageal reflux disease (GERD) to restore and maintain lower esophageal sphincter and angle of His anatomy without encircling and putting pressure on the food passageway, thereby avoiding side effects such as dysphagia and bloating seen with traditional fundoplication. This study reports the clinical outcomes with RefluxStop at 4 years following implantation of the device.MethodsA prospective, single arm, multicenter clinical investigation analyzing safety and effectiveness of the RefluxStop device in 50 patients with chronic GERD.ResultsAvailable data are presented for 44 patients at 4 years with the addition of three patients at 3 years carried forward. At 4 years, median GERD-HRQL score was 90% reduced compared to baseline. Two patients (2/44) used regular daily proton pump inhibitors (PPIs) despite subsequent 24-h pH monitoring off PPI therapy yielding normal results. There were no device-related adverse events (AEs), esophageal dilations, migrations, or explants during the entire study period. AEs reported between 1 and 4 years were as follows: one subject with heartburn and a pathologic pH result with device positioned too low at surgery; one subject with dysphagia, thus, 46/47 patients reported no dysphagia-related AEs between years 1 and 4. Two patients (2/47) were dissatisfied with treatment despite normal 24-h pH monitoring, of whom one had manometry-verified dysmotility at 6 months, indicating dissatisfaction for reasons other than acid reflux.ConclusionThese results confirm the excellent and already published 1-year results as stable in the long-term, supporting the safety and effectiveness of the RefluxStop device in treating GERD for over 4 years. GERD-HRQL score, pH testing, and PPI usage indicate treatment success without dysphagia or gas-bloating and only minimal incidence of other AEs. This favorably low rate of AEs is likely attributable to RefluxStop’s dynamic physiologic interaction and non-encircling nature.

Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands

Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre.

Apatinib plus chemotherapy is associated with an improved tumor response, survival and tolerance compared with chemotherapy alone for advanced lung adenocarcinoma treatment.

Apatinib plus chemotherapy demonstrates good efficacy in multiple advanced carcinomas; however, its use in patients with advanced lung adenocarcinoma (LUAD) has not yet been assessed. The present study evaluated the potential benefits of apatinib plus chemotherapy in patients with advanced LUAD. A total of 145 patients with advanced LUAD and negative driver genes who received apatinib plus chemotherapy (n=65) or chemotherapy alone (n=80) were analyzed. The overall response rate was significantly improved by apatinib plus chemotherapy vs. chemotherapy alone (53.8 vs. 36.3%; P=0.034). Moreover, progression-free survival (PFS) was significantly longer in patients who received apatinib plus chemotherapy, compared with those who received chemotherapy alone [median (95% CI), 13.4 months (11.5-15.3) vs. 8.2 months (6.9-9.5); P<0.001], as was overall survival (OS) [median (95% CI), 23.1 months (not reached) vs. 17.0 months (14.6-19.4; P=0.001). Following adjustment by multivariate Cox regression analysis, apatinib plus chemotherapy was associated with a significantly longer PFS [hazard ratio (HR), 0.444; P<0.001] and OS (HR, 0.347; P<0.001), compared with chemotherapy alone. Subgroup analyses revealed that PFS and OS were significantly improved following apatinib plus chemotherapy vs. chemotherapy alone (all P<0.05) in patients receiving first- or second-line treatment. Notably, the incidence of hypertension was significantly increased following apatinib plus chemotherapy vs. chemotherapy alone (43.1 vs. 25.0%; P=0.021), whereas the incidence of other adverse events was not significantly different between the two treatment groups (all P>0.05). In conclusion, apatinib plus chemotherapy is associated with an improved treatment response and survival compared with chemotherapy alone, with a tolerable safety profile in patients with advanced LUAD.

Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials.

To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight. A search formula was written using search terms such as "tirzepatide," "overweight," and "obesity." A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023. A total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), p < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = -4.08, 95% CI (-5.77, -2.39), p < 0.00001], [MD = -7.71, 95% CI (-10.17, -5.25), p < 0.00001], [MD = -9.15, 95% CI (-10.02, -8.29), p < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = -5.65, 95% CI (-7.47, -3.82), p < 0.001], [MD = -10.06, 95% CI (-12.86, -7.25), p < 0.001], [MD = -10.63, 95% CI (-12.42, -8.84), p < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group (p > 0.05). Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.

P524 Etrasimod shows low risk of adverse events following concomitant use with opioids or antidepressants in patients with ulcerative colitis

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).1 Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.2 This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. Methods Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).3 Results Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. Conclusion The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.

Efficacy and safety of camrelizumab-based comprehensive treatment for non-small cell lung cancer: a systematic review and meta-analysis.

Many studies show that camrelizumab combination therapy can significantly improve progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC). However, the time of camrelizumab to market is short, and there is no systematic evaluation of camrelizumab-based comprehensive treatment of NSCLC. To systematically evaluate the efficacy and safety of camrelizumab in comprehensively treating NSCLC. A systematic review and meta-analysis. Databases, including PubMed, Web of Science, Embase, and Cochrane, were searched by computer before August 2023 based on Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and reports on the efficacy and safety of camrelizumab-based treatment for NSCLC were collected, and RevMan 5.4 software was employed for meta-analysis finally. Totally, 5 RCTs, 2 cohort studies, and 12 single-arm studies were included. The meta-analysis results revealed that, compared with the treatment without camrelizumab, the camrelizumab-based combination treatment considerably extended the OS (hazard ratio (HR) = 0.60, 95% confidence interval (CI): (0.44-0.82), p < 0.01), PFS (HR = 0.42, 95% CI: (0.28-0.63), p < 0.01), and event-free survival (EFS) (HR = 0.55, 95% CI: (0.44-0.68), p < 0.01). The median objective response rate in single-arm studies was 41% (95% CI: 28%-53%), and the disease control rate was 84% (95% CI: 78%-89%). Furthermore, in terms of the occurrence of grades 3-5 adverse events, the incidence of neutropenia was lower in the camrelizumab combination group than in the control group, while the incidence of leukopenia and rash was higher than in the combination group, and no significant difference was revealed in the incidence of other adverse events. Among single-arm studies, the incidence of grades 3-5 adverse events did not exceed 10%. Treatment combined with camrelizumab can effectively prolong OS, PFS, and EFS in NSCLC patients with good safety, camrelizumab combined with chemotherapy is an effective treatment option for NSCLC patients.

Endoscopic gallbladder inside-stenting combined with aspirated lavage for calculous cholecystitis in poor surgical candidates: a prospective pilot study

Although long-term stent placement via endoscopic gallbladder stenting (EGBS) reportedly reduces cholecystitis recurrence in patients unfit to undergo cholecystectomy, it can increase the frequency of other late adverse events (AEs) such as cholangitis. This study aimed to examine the feasibility of endoscopic gallbladder inside-stenting (EGB-IS) with lavage and aspiration. This prospective, single-center, pilot study enrolled 83 patients with acute calculous cholecystitis who were poor candidates for surgery. A dedicated catheter with eight side holes was used for lavage and aspiration, and a dedicated single-pigtail stent equipped with a thread was used for EGB-IS. Outcomes such as technical success, clinical success, early AEs, recurrence of cholecystitis, and other symptomatic late AEs associated with EGB-IS with lavage and aspiration were evaluated. The technical and clinical success rates were 80.7% (67/83) and 98.5% (66/67), respectively. The rate of early AEs was 3.6% (3/83). The rate of recurrent cholecystitis was 4.5% (3/66) and that of symptomatic late AEs (besides cholecystitis) was 6.1% (4/66). Consequently, the rate of overall late AEs (cholecystitis plus other events) was 10.6% (7/66). The 1-, 2-, and 3-year cumulative incidence rates of all late AEs were 3.2%, 11.2%, and 18.9%, respectively. EGB-IS with lavage and aspiration for calculous cholecystitis showed promising results in poor surgical candidates. EGB-IS may be useful when EGBS with long-term stent placement is planned, since prevention of cholecystitis recurrence, without a rise in the incidence of other AEs, is anticipated.

Feasibility of apalutamide combined with androgen deprivation therapy and short-course low-dose prednisone in treating metastatic hormone-sensitive prostate cancer: a pilot randomized controlled trial.

The role of prednisone in the prevention of androgen receptor antagonist-related rash and treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This pilot trial (ChiCTR2200060388) aimed to investigate the feasibility of apalutamide combined with androgen deprivation therapy (ADT) and short-course low-dose prednisone in the treatment of mHSPC. All patients received apalutamide and ADT and were randomly divided into two groups based on the administration of oral prednisone or not (control group). The primary endpoint was the incidence of rash. The secondary endpoint included the proportions of patients with a decline in PSA ≥50% from baseline, PSA ≥90% from baseline, and decreased to PSA ≤0.2 ng/mL. Between June 2021 and March 2022, a total of 83 patients were enrolled (41 in the prednisone group and 42 in the control group). During the 6-month follow-up, the incidence of rash was significantly lower in the prednisone group compared with the control group (17.1% vs. 38.1%, P=0.049). There were no significant differences in the incidence of other adverse events, the number of patients who required dose adjustment (reduction, interruption, or discontinuation) of apalutamide due to rash, the number of patients with prostate-specific antigen (PSA) decreased by ≥50%, the number of patients with PSA decrease ≥90%, and the number of patients with PSA ≤0.2 ng/mL between the two groups. All patients with diabetes had stable glycemic control with no glucose-related adverse events. In patients with mHSPC, the addition of short-course low-dose prednisolone to apalutamide plus ADT can reduce the incidence of rash without risk of other adverse events.

The Use of Dexmedetomidine in Preterm Infants: A Single Academic Center Experience.

Preterm newborns (PTNBs) often require sedation and analgesia. Dexmedetomidine (DEX) is used to provide sedation in extremely PTNBs, even though information on such use is limited. The objective of this research is to describe the use of DEX in these patients in a single academic center. This is a retrospective study of PTNBs receiving DEX from January 1, 2010, through December 31, 2018, at the Cleveland Clinic Children's Hospital, a tertiary academic center operating 2 Level III and 1 Level IV neonatal intensive care units (NICUs). Inclusion criteria were gestational age (GA) <36 weeks and receipt of DEX for >2 days. Adequacy of clinical response was based on achieving Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores <3. Hypotension, bradycardia, and respiratory depression were recorded as the incidence as adverse events. A total of 105 patients were included. The birth weight median was 870 g (IQR, 615-1507); the GA median was 26 weeks (IQR, 24-31). The duration of DEX infusion averaged 7 days. The DEX dose averaged 0.4 mcg/kg (IQR, 0.3-0.45). Bradycardia was observed in 35 patients (57%) weighting <1 kg and in 7 patients (18%) >1 kg (p < 0.01). There was no difference in the incidence of other adverse events between these groups. However, infants <1 kg required more pharmacologic interventions to maintain N-PASS score <3. DEX was well tolerated overall and provided adequate sedation to PTNBs in this cohort. From this study, we recommend a starting dose of 0.2 to 0.4 mcg/kg/hr and titrating up hourly until adequate sedation is achieved.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study

BackgroundThis study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs).MethodsThe study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort.ResultsA total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7–51.2] in the MTX cohort and 24.3 months (95% CI: 16.6–32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8–35.2) in the MTX cohort and 32 months (95% CI: 27.6–36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts.ConclusionsThis was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses.Classification of evidenceThis study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate − based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Evaluation of SARS-CoV-2 vaccination in pregnant and breastfeeding women

ObjectivesWe aimed to assess the safety experience of women vaccinated with vaccines against SARS-CoV-2 during breastfeeding or pregnancy. MethodsVia an online questionnaire, we have inquired about the safety experience of 2192 pregnant or breastfeeding women vaccinated against SARS-CoV-2, including the incidence of adverse events (AEs), pregnancy outcomes, and confirmed infection with SARS-CoV-2. ResultsThe incidence of other AEs was higher in women vaccinated during breastfeeding. Significant differences were observed for fatigue (relative risk [RR] 1.230, 95% confidence interval [CI] 1.051-1.444, P = 0.0098), headache (RR 1.822, 95% CI 1.379-2.418, P <0.0001), myalgia (RR 1.633, 95% CI 1.269-2.110, P <0.0001), chills (RR 2.027, 95% CI, P <0.0001), subfebrile temperature ≤38°C (RR 1.697, 95% CI 1.240-2.335, P = 0.0007), arthralgia (RR 1.924, 95% CI 1.340-2.776, P = 0.0002), fever >38°C (RR 6.410, 95% CI 2.890-14.30, P <0.0001), and shivers (RR 2.204, 95% CI 1.264-3.863, P = 0.0049). No pattern of serious AEs emerged. Menstrual cycle bleeding disorders occurred in 0.7% of breastfeeding women after the first dose and 0.5% after the second dose. One spontaneous abortion occurred; 93.1% of pregnancies were carried to term, 5.6% late preterm, 0.9% moderate preterm, and 0.3% very preterm. Two children had congenital defects. Vaccine efficacy was 96.3%. ConclusionThe safety profile of SARS-CoV-2 vaccines in pregnant and breastfeeding women was similar to the general population. Breastfeeding women experienced higher AE rates than pregnant women, presumably due to immune alterations in pregnancy.

Safety and efficacy in pediatric secondary intraocular lens implantation, in-the-bag versus sulcus implantation: a multicenter, single-blinded randomized controlled trial

BackgroundTreatment of pediatric cataract remains challenging because of the extremely high incidence of postoperative adverse events (AEs), especially the AEs related to the locations of secondary implanted intraocular lens (IOL). There are two common locations for secondary IOL implantation in pediatric aphakic eyes: ciliary sulcus or in-the-bag implantation. However, there are currently no large, prospective studies comparing complication rates and visual prognosis of in-the-bag versus ciliarysulcus secondary IOL implantation in pediatric patients. Whether or how much secondary in-the-bag IOL implantation benefits the pediatric patients more than sulcus implantation and deserves to be performed routinely by surgeons remains to be elucidated. Here, we describe the protocol of a randomized controlled trial (RCT) designed to evaluate the safety and efficacy of two approaches of IOL implantation in pediatric aphakia.MethodsThe study is a multicenter, single-blinded RCT with 10 years of follow-up. Overall, a minimum of 286 eyes (approximately 228 participants assuming 75% have two study eyes) will be recruited. This study will be carried out in four eye clinics across China. Consecutive eligible patients are randomized to undergo either secondary in-the-bag IOL implantation or secondary sulcus IOL implantation. Participants with two eyes eligible will receive the same treatment. The primary outcomes are IOL decentration and the incidence of glaucoma-related AEs. The secondary outcomes include the incidence of other AEs, IOL tilt, visual acuity, and ocular refractive power. Analysis of the primary and secondary outcomes is to be based on the intention-to-treat and per-protocol analysis. Statistical analyses will include the χ2 test or Fisher’s exact test for the primary outcome, mixed model and generalized estimated equation (GEE) model for the secondary outcome, Kaplan–Meier survival curves for the cumulative probability of glaucoma-related AEs over time in each group.DiscussionTo the best of our knowledge, this study is the first RCT to evaluate the safety and efficacy of secondary IOL implantation in pediatric aphakia. The results will provide high-quality evidence for the clinical guidelines for the treatment of pediatric aphakia.Trial registrationClinicalTrials.gov NCT05136950. Registered on 1 November 2021.

Efficacy and safety of oxymetazoline for the treatment of rosacea: A meta-analysis.

Since there is currently no conclusion on the efficacy and adverse effects of oxymetazoline, this meta-analysis attempts to explore its efficacy and adverse events, so as to provide guidance for clinical medication. We searched PubMed, Embase, and Cochrane Library from the establishment of the database to May 2021. We included studies that patients were randomly assigned to receive oxymetazoline or vehicle, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results show that the 3 (RR = 1.76, 95% CI: 1.53-2.03), 6 (RR = 1.71, 95% CI: 1.47-2.00), 9 (RR = 1.63, 95% CI: 1.40-1.90), 12 (RR = 1.41, 95% CI: 1.18-1.67) -hours CEA success rate and the 3 (RR = 1.65, 95% CI: 1.34-2.03), 6 (RR = 1.75, 95% CI: 1.43-2.14), 9 (RR = 1.63, 95% CI: 1.33-2.00), 12 (RR = 1.78, 95% CI: 1.45-2.18) -hours SSA success rate after oxymetazoline treatment for rosacea is significantly higher than that of vehicle. Additionally, the pooled results show that the incidence of TEAEs after treatment with oxymetazoline is significantly higher than that of vehicle (RR = 1.34, 95% CI: 1.10-1.2). However, our analysis of specific adverse events found that the oxymetazoline group was only significantly higher than the vehicle group in the incidence of application-site dermatitis (RR = 8.91, 95% CI: 1.76-45.23), and there was no statistical significance in the difference in the incidence of other adverse events. Oxymetazoline is effective and can be selected for the treatment of persistent facial erythema of rosacea. Additionally, application-site dermatitis was the most important one.

A novel prednisone premedication protocol significantly decreases infusion‑related reactions of rituximab in newly diagnosed diffuse large B‑cell lymphoma.

Rituximab is a widely used anti-CD20 monoclonal antibody with a high incidence of infusion-related reactions (IRRs) during administration. Reducing the incidence of IRRs remains problematic in hematological practices. In the present study, a novel strategy of a prednisone pretreatment regimen was designed similar to the combination of rituximab, cyclophosphamide, epirubicin, vincristine and prednisone (R-CHOP) with the aim of exploring the effect on the incidence of IRRs to rituximab in patients with diffuse large B-cell lymphoma (DLBCL). A prospective, randomized (1:1) and controlled study was conducted in three regional hospitals in two groups (n=44 for each group): i) A control group treated with standard R-CHOP-like regimen; and ii) a group receiving a prednisone-pretreatment, modified R-CHOP-like protocol for newly diagnosed patients with DLBCL. The primary endpoint was to assess the incidence of IRRs to rituximab, as well as the association of IRRs with the efficacy of treatment. The second endpoint involved clinical outcomes. The total incidence of IRRs to rituximab in the treatment group was significantly lower compared with that in the control group (15.9 vs. 43.2%; P=0.0051). The different grade incidence of IRRs was lower in the treatment group compared with that in the control group (P=0.0053). In total, 29.5% of patients (26/88) experienced >1 IRR episode. The incidence of IRRs in the pre-treatment group was decreased compared with that in the control group in the 1st cycle (15.9 vs. 43.2%; P=0.0051) and 2nd cycle (6.8 vs. 27.3%; P=0.0107). The overall response rate was similar between the two groups (P>0.05). Median progression-free survival and median overall survival time were not statistically distinct between the two groups (P=0.5244 and P=0.5778, respectively). Grade ≥III toxicities mainly included vomiting and nausea (<20%), leukopenia and granulocytopenia (<20%), and alopecia (<25%). No death events were reported. Apart from IRRs to rituximab, the incidence of other adverse events was similar in both groups. The novel prednisone-pretreatment R-CHOP-like protocol in the present study significantly decreased the total and different grade incidences of IRRs to rituximab among newly diagnosed patients with DLBCL. This clinical trial was retrospectively registered with the Chinese Clinical Trial Registry (registration number, ChiCTR2300070327; date of registration, 10 April 2023).

Effectiveness and safety of intrathecal morphine for percutaneous endoscopic lumbar discectomy under low-dose ropivacaine: a prospective, randomized, double-blind clinical trial

BACKGROUND CONTEXTPercutaneous endoscopic lumbar discectomy (PELD) is a surgical setting that requires minimal motor impairment. Low-dose spinal ropivacaine induces little motor blockade and could be ideal for maintaining safety of PELD, but its analgesic efficacy is questionable. An adjunct analgesic approach is needed to maximize the benefits of low-dose spinal ropivacaine for PELD. PURPOSEThis study aimed to explore the effectiveness and safety of 100 µg intrathecal morphine (ITM) as an adjuvant analgesic method for PELD under low-dose spinal ropivacaine. STUDY DESIGNA double-blind, randomized, placebo-controlled trial. Trial registration: ChiCTR2000039842 (www.chictr.org.cn). SAMPLENinety patients scheduled for elective single-level PELD under low-dose spinal ropivacaine. OUTCOME MEASURESThe primary outcome was the overall intraoperative visual analogue scale (VAS) score for pain. Secondary outcomes were intraoperative VAS scores assessed at multiple timepoints; intraoperative rescue analgesic requirement; postoperative VAS scores; disability scale; patients’ satisfaction with anesthesia; adverse events; and radiographic outcomes. METHODSPatients were randomized to receive low-dose ropivacaine spinal anesthesia with (ITM group, n=45) or without (control group, n=45) 100 µg ITM. RESULTSThe overall intraoperative VAS score in the ITM group was significantly lower than that in the control group (0 [0, 1] vs 2 [1, 3], p<.001). During operation, the VAS scores at cannula insertion, 30 minutes after insertion, 60 minutes after insertion, and 120 minutes after insertion were all significantly lower in the ITM group (all p<.05). Less patients in the ITM group required rescue analgesia during operation compared with those in the control group (14% vs 42%, p= .003). The VAS score for back pain in the ITM group was lower than that in the control group at 1 hour, 12 hours, and 24 hours postoperatively. Besides, the satisfaction score in the ITM group was significantly higher than that in the control group (p=.017). For adverse events, 8/43 of ITM and 1/44 of control participants experienced pruritus (p=.014), with a relative risk (95% confidence interval) of 8.37 (1.09–64.16). The incidence of other adverse events was similar between the two groups. Of note, respiratory depression occurred in one ITM-treated patient. CONCLUSIONThe addition of 100 µg ITM to low-dose ropivacaine appears to be effective in analgesia without compromised motor function for PELD; however, ITM increased the risk of pruritus and clinicians should be vigilant about its potential risk of respiratory depression.

The efficacy and safety of using pyrotinib combined with capecitabine as neoadjuvant therapy in elderly patients with HER2-positive breast cancer: a single-arm prospective clinical trial.

Pyrotinib combined with capecitabine has been approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in China. To date, the management of early-stage or locally advanced HER2-positive breast cancer in the clinic remains challenging. We conducted this trial to investigate the efficacy and safety of pyrotinib combined with capecitabine as neoadjuvant therapy (NAT) in elderly patients with HER2-positive breast cancer. Due to the stimulation of blood vessels by chemotherapy drugs, the elasticity of blood vessels in the elderly decreases, and then chemotherapy infusion is more likely to lead to phlebitis. Both pyrotinib and capecitabine can be taken to facilitate home treatment for elderly patients with HER2-positive breast cancer (BC). From January 2020 to March 2021, patients aged between 70 and 81 years old with stage IIA-IIIB HER2-positive breast cancer were screened, enrolled, and assigned to receive six cycles of pyrotinib (320-400 mg, orally, once daily) plus capecitabine (1,250 mg/m2, orally, twice daily) on days 1-14 in every 21-day cycle. The primary endpoint was the objective response rate (ORR). Adverse events (AEs) were assessed in every neoadjuvant cycle. Surgery was performed after the last cycle, and the total pathological complete response (tpCR) was evaluated postoperatively. Of the 23 patients enrolled, the ORR was 100% (23/23; 95% confidence intervals: 85 to 100). All patients underwent surgery with a tpCR rate of 43.5% (10/23; 95% confidence intervals: 23 to 66). The most common AE was diarrhea, occurring in 19 of 23 patients (82.6%); most of these patients sustained mild diarrhea (Grade 1 or Grade 2) and only three had moderate diarrhea (Grade 3). The incidences of other AEs, including weakness, loss of appetite, leukopenia, nausea, vomiting, hand-foot syndrome, etc., were low and the symptoms were mild. No severe AEs (Grade 4 or 5) were observed throughout the treatment. In our study, pyrotinib combined with capecitabine as neoadjuvant therapy in elderly women with HER2-positive breast cancer is safe and showed efficacy in this population, which may be widely used as a protocol for clinical neoadjuvant therapy.

Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes Mellitus Fasting During Ramadan: A Real-World Study from Bangladesh.

In Bangladesh, there is a large population of Muslims with type 2 diabetes mellitus (T2DM) who fast during Ramadan. Changes in the pattern of meal and fluid intake during this long-fasting hours may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. Our key point of focus was to evaluate the efficacy and safety of Empagliflozin, a sodium-glucose co transporter 2 inhibitor (SGLT2i), in patients with T2DM while fasting during Ramadan. This was a 24-weeks, multi-centre, open-label, two-arm parallel-group study. In this prospective type of observational study, we enrolled patients taking Empagliflozin and Metformin with or without a DPP-4 inhibitor in one group (n = 274) and a parallel group (n = 219) who were treated with Metformin with or without a DPP-4 inhibitor. The primary endpoint of this study was HbA1c reduction, weight loss and the number of reported or symptomatic hypoglycemic events. In secondary endpoints, we evaluated the changes from baseline in blood pressure, estimated glomerular filtration rate (eGFR), serum creatinine, and serum electrolyte, the proportion of volume depletion (≥1 event) and incidence of other adverse events (AEs) of interest potentially related to SGLT2 inhibitor. During Ramadan, HbA1c reduction was significant in Empagliflozin arm (-0.49% vs -0.12%); [p < 0.001]. From before to the end of the study, significant weight reduction was seen in the Empagliflozin arm (-1.4 kg vs -0.09 kg); [p < 0.001]. We observed no significant increase in the incidence of hypoglycemia (0.7% vs 0.4%, p = 0.267) and volume depletion (2.6% vs 1.8%; p = 0.55) in both arm. All these milder forms events did not require any hospital admission. There was no report of serious adverse events or any discontinuation, or reduction of prescribed doses of empagliflozin during Ramadan. Empagliflozin is efficacious and safe for treating adults with T2DM during Ramadan.

Efficacy and Safety of Adjunctive Recombinant Human Interleukin-2 for Patients with Pulmonary Tuberculosis: A Meta-Analysis.

The results of previous clinical trials evaluating the efficacy and safety of recombinant human interleukin-2 (rhuIL-2) for adult patients with pulmonary tuberculosis showed inconsistent results. Accordingly, a comprehensive systematic review and meta-analysis was performed. Relevant randomized controlled trials (RCTs) were retrieved by searching the PubMed, Embase, Cochrane's Library, Web of Science, Wanfang, and CNKI databases. A random-effects model was used to combine the results. 18 RCTs with 2630 patients were included in this meta-analysis. Pooled results showed that adjunctive rhuIL-2 significantly increased the odds of sputum culture conversion to negative (risk ratio [RR]: 1.27, 95% CI: 1.09 to 1.47, p=0.002, I 2 = 80%), sputum smear conversion to negative (RR: 1.35, 95% CI: 1.17 to 1.57, p < 0.001, I 2 = 83%), radiographic focus absorption (RR: 1.17, 95% CI: 1.06 to 1.30, p=0.002, I 2 = 72), and cavity closure (RR: 1.24, 95% CI: 1.09 to 1.40, p < 0.001, I 2 = 23). The use of rhuIL-2 was not related to any severe adverse events which led to discontinuation of the treatment. Results showed that rhuIL-2 was related to an increased risk of fever (RR: 2.46, 95% CI: 1.29 to 4.70, p=0.006, I 2 = 0%). The incidence of other adverse events, such as musculoskeletal pain, hepatic injury, and renal toxicity, was not significantly different between groups (p all >0.05). rhuIL-2 is an effective adjunctive immunotherapy for patients with pulmonary tuberculosis.

Comparison of efficacy and safety of three different drugs combined with radiotherapy in the treatment of patients with advanced pancreatic cancer

Purpose: To investigate the clinical efficacy and safety of three different drugs combined with radiotherapy, viz, apatinib mesylate combined radiotherapy (group A), gemcitabine combined oxaliplatin (group B), and Huachansu capsules combined radiotherapy (group C)] in advanced pancreatic cancer patients.&#x0D; Methods: A total of 174 patients with advanced pancreatic cancer treated in Yantai Qishan Hospital, Yantai, China from June 2015 to December 2016 were randomly and evenly divided into groups A, B, and C. The incidence of adverse reactions during treatment, immune reaction, efficacy, quality of life, and survival were compared among the three groups after four courses of treatment.&#x0D; Results: Compared with groups B and C, the incidence of nausea and vomiting was higher in group A (p &lt; 0.05), but the incidence of other adverse events was not significantly different (p &gt; 0.05). Group A showed higher response rate and disease control rate, higher CD4+, CD4+/CD8+ levels and QOL scores, as well as lower CD8+ level in peripheral blood after treatment than groups B and C (p &lt; 0.05). Group A also exhibited longer median OS and median PFS, and higher 2-year survival than groups B and C (p &lt; 0.05).&#x0D; Conclusion: Among the three different drug treatments combined with radiotherapy, apatinib mesylate combined radiotherapy enhanced efficacy and quality of life, and lengthen the survival time of advanced pancreatic cancer patients. However, additional clinical trials are required to validate these findings.