Routine Regimen Research Articles

P-631 Extended letrozole regimen versus routine letrozole regimen in women with polycystic ovary syndrome undergoing their first ovulation induction cycle

Abstract Study question Whether an extended letrozole regimen could result in a higher ovulatory rate than a routine regimen in PCOS women undergoing their first ovulation induction cycle. Summary answer PCOS women using the extended letrozole regimen failed to obtain a statistically higher rate of ovulation in comparison with the routine letrozole regimen. What is known already Letrozole has become the first-line agent for ovulation induction, however, nonresponsive cycles occurred in 10-58.8% of PCOS women during their ovulation induction therapy with letrozole alone. The extended letrozole regimen has been demonstrated to be a feasible method for inducing ovulation in those nonresponders. However, whether it could be applied to all the PCOS women as a first choice in the induction of ovulation remains to be explored. Study design, size, duration This is a prospective randomized controlled trial including 148 women with PCOS undergoing their first ovulation induction cycle with letrozole from January 2021 to October 2022. Participants/materials, setting, methods Participants were randomly assigned to receive an extended letrozole regimen (5 mg letrozole daily for 7 days) or a routine regimen(5 mg letrozole daily for 5 days) for one treatment cycle. Ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, the rate of multiple pregnancies. Main results and the role of chance The ovulation rate among women receiving a 7-day regimen was slightly higher than the rate with a 5-day regimen, but it did not reach a statistical significance in both the intention-to-treat analysis (90.54%[67/74]vs. 82.43%[59/74], P = 0.065) and per-protocol analysis (90.54%[67/74]vs. 84.29%[59/70], P = 0.257). The number of preovulatory follicles was nearly identical in the two groups (1.39±0.62 vs.1.37±0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. In the per-protocol analysis, the rates of clinical pregnancy (20.27%[15/74]vs.16.95%[10/70], P = 0.343) and live birth (13.51%[10/74]vs.11.43%[8/70], P = 0.976) did not differ significantly between treatment groups. Moreover, all the conceptions were singletons without neonatal defects. Limitations, reasons for caution The major concern of the current research is its single-centre and open label nature. Additionally, the limited number of lean PCOS women with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restrict the generalizability of our findings. Wider implications of the findings Letrozole 5-day regimen remains to be the first choice for PCOS women undergoing ovulation induction therapy. Additional prospective trials with a larger sample size and different subgroups of PCOS are needed to assess the ovulatory effects of different letrozole treatment duration. Trial registration number ChiCTR2100042082

Impact of Anaerobic Exercise Integrated Into Regular Training on Experienced Judo Athletes: Running Vs. Repetitive Throws.

Kamandulis, S, Dudėnienė, L, Snieckus, A, Kniubaite, A, Mickevicius, M, Lukonaitiene, I, Venckunas, T, Stasiule, L, and Stasiulis, A. Impact of anaerobic exercise integrated into regular training on experienced judo athletes: running vs. repetitive throws. J Strength Cond Res 38(9): e489-e495, 2024-Anaerobic training in high-level athletes is of considerable interest to practitioners aiming to optimize performance. This study compared the impact of interval anaerobic training (IAT) sessions consisting of either high-intensity running or throwing that were performed twice a week together with regular judo training on the anaerobic and aerobic performance of experienced judo athletes. Employing a repeated-measures, counterbalancing, research design, 12 national team judo athletes (7 women and 5 men; mean age, 20.4 ± 0.95 years; mean judo training experience, 13.4 ± 1.4 years; competitive level, black belt first and second Dan) performed each IAT modality for 6 weeks, for a full training cycle of 12 weeks. Assessments of their anaerobic fitness (Cunningham and Faulkner Anaerobic Treadmill Test), sport-specific anaerobic fitness (Special Judo Fitness Test [SJFT]), and aerobic capacity (maximal incremental treadmill running test) were performed before, after 6 weeks, and after 12 weeks of training. The uphill running performance improved by 13.1% over the 12-week period ( p = 0.047). Simultaneously, there was a 9.0% improvement in the SJFT index and a 6.9% increase in the number of throws ( p = 0.011 and p = 0.017, respectively). Although a trend for throwing drills being more effective than interval sprint running was observed, the interaction effect lacked statistical significance ( p = 0.074). Moreover, no substantial changes were noted in aerobic endurance markers. In conclusion, this study suggests that incorporating specific and nonspecific high-intensity drills into a routine training regimen may enhance anaerobic capacity among well-trained judo athletes, potentially leading to favorable competitive outcomes.

تقييم نشاط التئام الجروح وتحفيز موت الخلايا المبرمج لمشتقات الكينازولينون الجديدة

Background: Chemotherapeutic medication treatment for cancer is typically used in conjunction with other techniques as part of a routine regimen. It is well established that the capacity of different chemotherapeutic drugs to induce apoptosis is correlated with their anticancer efficacy. Quinazolinone-based drugs have demonstrated excellent responses from several cancer cell types. These substances have a lot of potential for use as building blocks in the creation of apoptosis inducers. Objective: To assess the new quinazolinone derivatives (M1 and M2) that were recently synthesized for their potential to halt wound healing and to use the acridine orange/propidium iodide (AO/PI) double stain to assess their capacity to induce apoptosis in the chosen cancer cell lines. Methods: Using the breast carcinoma cell line (MCF-7) and the lung adenocarcinoma cell line (A549), two quinazolinone derivatives (M1 and M2) were investigated for their capacity to inhibit wound healing and induce apoptosis. Results: In both cell lines, the chemicals were found to be effective inducers of apoptosis and to considerably limit wound healing. Conclusions: In cancer cell lines (MCF-7 and A549), compounds M1 and M2 efficiently inhibited wound repair and triggered apoptosis.

Effects of Circuit Training on Sports Performance of Semi-professional Roll Ball Players

This study aimed to determine the six-week circuit training's effect on the components of fitness of semi-professional roll ball players. To accomplish the goal of this study, sixty (60) roll ball players between the ages of fourteen and eighteen were chosen, and they were split into two equal groups: An experimental group (n = 30), and a control group (n = 30). The full duration of the circuit training program was six weeks with three sessions per week. In addition, the experimental group had a circuit training regimen which was added to their regular traditional regimen. The control group did not have a specified training program instead they had their routine regular regimen. The physical fitness variables selected as dependent variables were speed, agility, explosive power, upper body and shoulder girdle strength endurance, abdominal strength, and endurance. The speed was determined through the 50m dash run, Agility was measured with the 4 x 10m shuttle run performance, the explosive power was determined by Standing broad jump, and the abdominal strength was measured through bent knee sit-ups and the upper body and shoulder girdle strength were determined from pull-ups. The tests were conducted before and after the six weeks of circuit training. An eight-station circuit was formulated, and an adaptation period of two weeks was provided. Every two weeks, we added at least ten seconds to each station’s exercise. The data collected was analyzed by paired t-test to examine if any significant difference exists or not between pre–test and post-test scores of the experimental group as well as between the pre and post–test scores of the control group. An unpaired t-test has been used for determining if the difference between scores in the pretest of experimental and control groups is significant and for post-test equality of experimental and control groups as well. Mean, SD, and t-ratio were tested. Accordingly, it was determined that a six-week circuit training workout was highly effective as it had visible effects on all the selected parameters of physical fitness.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer’s disease

ABSTRACT Background Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties. Objective This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients. Methods This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester. Results The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter silymarin = 13.37 ± 6.81, p < 0.001). Conclusion Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

P947 medical cannabis increases appetite but not body weight in patients with inflammatory bowel diseases

Abstract Background Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD. Methods An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment. Results Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P&amp;lt;0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010). Conclusion Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.

Implementing routine monitoring for nuclease contamination of equipment and consumables into the quality Management system of a laboratory

Nucleases are ubiquitous in the environment, present in biospecimens and widely used in many laboratory processes. However, in the wrong context, as contaminants, they have catastrophic potential because of their ability to rapidly degrade nucleic acids whilst retaining high resilience to inactivation. Although laboratories undertake rigorous precautions to prevent nuclease contamination, such measures are not infallible. In 2015, we devised and integrated a novel routine nuclease testing regimen into our Quality Management System that uses cleavable, fluorescent DNA and RNA substrates to detect, monitor and control for nuclease contamination in our laboratory processes, equipment and consumables. The testing regimen enables us to identify higher-risk activities, design our laboratory workflows such that risk is minimized and help fulfil our obligations in respect of ISO 20387:2018 General Requirements for Biobanking and ISO 17025 Testing and Calibrations Laboratory standards, both of which stipulate that environmental conditions in our laboratory must be monitored with defined quality control criteria. In seventeen rounds of testing (30 Test Items per round), 1.1 % of RNase tests and 0.2 % of DNase tests returned elevated nuclease levels (≥2.90 x 10−9 U RNase or 1.67 x 10−3 U DNase) and we were able to take remedial action. In no instance was an elevated nuclease level consequential in terms of an impact on sample quality. We present our protocols, results and observations.

The methodology of resistance training is crucial for improving short-medium distance front crawl performance in competitive swimmers: a systematic review and meta-analysis.

Resistance training is often a part of the routine training regimen for competitive swimmers. However, due to the variety of resistance training methodology, the results can be inconsistent and sometimes unsatisfactory. Clear recommendations are still lacking at present. 1) Quantify the impact of resistance training on swimmers' upper limb maximum strength, front crawl performance and key technical parameters; 2) Find out the key technical parameters for improving front crawl performance-stroke rate or length; 3) Through subgroup analysis determine the best methodology of resistance training to enhance the front crawl. Systematic search in the PubMed, Embase, and Web of Science databases. Meta-analyses using the inverse-variance are performed to compare swimmers' upper limb maximum strength, front crawl performance and key technical parameters in resistance training and habitual aquatic training. A subgroup analysis was performed to examine whether the results were affected by the methodology of resistance training. Thirteen studies (267 competitive swimmers) met the inclusion criteria. The results of meta-analysis showed that resistance training significantly improved upper limbs maximum muscle strength, and 25, 50, 100, and 200m front crawl performance in competitive swimmers. And improvements in swimming performance may simply resulted from resistance training increasing stroke rate rather than stroke length. In addition, the results of subgroup analysis showed that only concurrent resistance training (CRT) and power training (PT) ultimately improved swimming performance by increasing the maximum muscle strength of the upper limbs. Resistance training significantly enhances competitive swimmers' upper limb strength and front crawl performance across various distances. The improvement in performance is likely attributed to an increased stroke rate rather than stroke length. In addition, CRT and PT are particularly effective, indicating the importance of selecting the appropriate methodology of resistance training for optimal swimming performance enhancement. https://doi.org/10.17605/OSF.IO/3JEGW.

The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial.

The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18-70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).

Pharmacokinetic–pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses

IntroductionThe aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses.MethodsA population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations.ResultsA 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The fAUC/MIC or fT&amp;gt;MIC were calculated with a free BP fraction set at 0.4. For fAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. For fT&amp;gt;MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, a fT&amp;gt;MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L.DiscussionThe PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.

The hypoglycemic effects of Juglans regia L. internal septum in type 2 diabetic patients: A double-blind, randomized, placebo-controlled clinical trial.

The internal septum of J.regia is traditionally used to control diabetes, and its effectiveness has been shown in animal studies. Accordingly, human clinical trials are needed to confirm its effectiveness on hemoglobin A1c (HbA1c), fasting blood sugar (FBS), blood insulin level, and insulin resistance as a complementary for better control of type 2 diabetes. This study was a randomized, double-blinded, controlled trial. The lyophilized powder of extract of the internal septum of J.regia was used to fill the capsules. Sixty type 2 diabetic patients were randomly divided into two groups. 500 mg capsules three times daily before meal was added to their routine drug regimen, and HbA1c, FBS, and blood insulin level were checked at the baseline and after three months. Sixty patients completed the study. The mean(±SD) age of patients was 49.1(10.2) and 50.9(12.7) years in the placebo and J.regia groups, respectively. We observed that J.regia internal septum increases the level of HbA1c by about 0.02 units, but this effect was not significant (MD=0.02,95%CI=-0.36 to 0.40, P=0.93). Regarding the impact of capsules on insulin level, it seems that J.regia-containing capsules can raise insulin level by one unit. However, it was not significant (MD=1.01,95%CI=-0.86 to 2.88, P=0.28). As for FBS, it can cause a decrease of four units, but this effect is also not significant (MD=-3.98,95%CI=-18.33 to 10.37, P=0.58). Based on our study, the internal septum of J.regia has no significant effect on HbA1c, FBS, and insulin resistance. Moreover, no specific adverse reaction was observed in any of the patients.

Effect of Dexmedotomdine hydrochloride (Percedex®) on functional outcome of patients with moderate and severe traumatic brain injury

Traumatic brain injury (TBI) is considered among the leading causes of morbidity and mortality worldwide being associated with significant social and economic burden. The best sedative regimen in TBI patients is yet to be identified. This study was designed to determine the effects of dexmedotomdine hydrochloride (Percedex®, DEX) on functional outcome of patients with moderate and severe traumatic brain injury (TBI). This was a retrospective cohort study including patients with severe (3–8) and moderate (9–13) TBI referring to a level I trauma center. We studied two groups of patients, those receiving DEX or routine sedation regimen in neurointensive care unit (NICU). The main outcome measures were the Glasgow outcome scale extended (GOSE) at 3 and 6-month. We have also recorded ICU and hospital length of stay (LOS) and the tracheostomy rate. We included 138 patients in two study groups (each including 69). The baseline characteristics were comparable between groups. DEX was associated with lower LOS in hospital (p = 0.002) and NICU (p = 0.003). The GOSE was comparable between two study groups at 3 (p = 0.245) and 6-month (p = 0.497). Multivariate regression analysis revealed that after LOS of NICU and hospital stay adjustment, DEX group experienced significantly improved 6-month GOSE with the average improvement in score of 0.92 compared to the control group (p = 0.041). DEX administration in patients with moderate and severe TBI was associated with decreased NICU and hospital LOS and improved functional outcome at 6-month.

The Effect of Memantine Versus Folic Acid on Cognitive Impairment in Patients with Schizophrenia: A Randomized Clinical Trial.

Objective: Schizophrenia, as one of the most severe psychiatric diseases, has a chronic and debilitating process. The majority of patients with schizophrenia do not respond adequately to treatment with common antipsychotic drugs. Therapeutic problems induced by drug side effects as well as undesired results are major challenging issues regarding this disease. This study aimed at evaluating the effect of memantine supplementation on the improvement of cognitive symptoms in patients with schizophrenia. Method : The present clinical trial was performed on 50 patients with acute schizophrenia who were admitted to Kargarnejad Psychiatric Hospital in Kashan in 2022 and who were diagnosed as schizophrenia cases at least three months ago. Patients were randomly divided into either the intervention group (n = 25) or the placebo group (n = 25). The intervention group received 5 mg of memantine per day for three months. The dose of memantine in this group was increased to the maximum of 20 mg per day. The placebo group received 1 mg of folic acid per day for three months. Moreover, an identical routine schizophrenia therapeutic regimen was administered to all patients. The effectiveness of memantine was evaluated using the Wechsler Adult Intelligence Scale (WAIS-III), which assessed cognitive ability in older adults over a 12-week follow-up period. Results: The WAIS-III score in the 12th week of the study was significantly different between the placebo and intervention groups (P = 0.004), such that the score of the memantine group was higher than that of the placebo group. No significant difference was observed between the two groups in terms of drug side effects. Conclusion: Memantine can be supplemented in the treatment of schizophrenia so as to improve the cognitive symptoms of this disorder. However, subsequent studies involving larger sample sizes and different doses seem to be necessary to provide more accurate results in this respect.

Colchicine usage for prevention of post atrial fibrillation ablation pericarditis in patients undergoing high-power short-duration ablation.

Radiofrequency ablation (RFA) for atrial fibrillation (AF) has been associated with variable incidence (0.88%-10%) of pericarditis manifested as chest pain, possibly more prevalent with the advent of high-power short-duration (HPSD) ablation. This has led to the widespread use of colchicine in preventative protocols for postablation pericarditis. However, the efficacy of preventative colchicine has not been validated yet. To evaluate the efficacy of a routine postoperative colchicine regimen (0.6 mg twice a day for 14 days post-AF ablation) for prevention of postablation pericarditis in patients undergoing HPSD ablation. We retrospectively evaluated consecutive single-operator HPSD AF ablation procedures at our institution from June 2019 to July 2022. A colchicine protocol was introduced in June 2021 for the prevention of postablation pericarditis. All ablations were performed with 50 watts. Patients were divided into colchicine and noncolchicine groups. We recorded incidence of postablation chest pain, emergency room (ER) visit for chest pain, pericardial effusion, pericardiocentesis, any ER visit, hospitalization, AF recurrence, and cardioversion for AF within the first 30 days following ablation. We also recorded colchicine-related side effects and medication compliance. Two hundred and ninety-four consecutive HPSD AF ablation patients were screened for the study. After implementing the prespecified exclusion criteria, a total of 205 patients were included in the final analysis, yielding 101 patients in the colchicine group and 104 patients in the noncolchicine group. Both groups were well-matched for demographic and procedural parameters. There was no significant difference in postablation chest pain (9.9% vs. 8.6%, p = .7), pericardial effusion (2.9% vs. 0.9%, p = .1), ER visits (11.9% vs. 12.5%, p = .2), 30-day hospitalization for AF recurrence (0.9% vs. 0.96%, p = .3), and 30-day need for cardioversion for AF (3.9% vs. 5.7%, p = .2). Fifteen (15) patients had severe colchicine-related diarrhea, out of which 12 discontinued it prematurely. There were no major procedural complications in either group. In this single-operator retrospective analysis, prophylactic colchicine was not associated with significant reduction in the incidence of postablation chest pain, pericarditis, 30 day hospitalization, ER visits, or AF recurrence or need of cardioversion within first 30 days after HPSD ablation for AF. However, its usage was associated with significant diarrhea. This study concludes no additional advantage of prophylactic use of colchicine after HPSD AF ablation.

Towards a population pharmacokinetic/pharmacodynamic model of anti-VEGF therapy in patients with age-related macular degeneration

PurposeTo develop a population pharmacokinetic/pharmacodynamic model (popPKPD) of intravitreal bevacizumab treatment for neovascular age-related macular degeneration (nAMD) patients to learn about the PK/PD relationship and utilise it for dosing regimen decisions on future nAMD patients. MethodsThe Greater Manchester Avastin for Neovascularisation (GMAN) randomised clinical trial data was retrospectively utilised, and the best-corrected visual acuity (BCVA) and central macular retinal thickness (CRT, measured by optical coherence tomography) were the PD inputs to the model. Using the nonlinear mixed-effects method, the best PKPD structural model was investigated, and the clinical significance of the two different dosing treatment regimens (as-needed versus routine) was evaluated. ResultsA structural model to describe the change of BCVA from the baseline of nAMD patients was successfully obtained based on the turnover PD model concept (drug stimulates the “visual acuity response production”). The popPKPD model and simulation indicate that the routine regimen protocol improves patient visual outcome compared to the as–needed protocol.For the change in CRT, the turnover structural PKPD model was too demanding to fit to the given clinical data. ConclusionsThis is the first popPKPD attempt in nAMD treatment that shows the potential of this strategy to understand/inform the dosing regimen. Clinical trials with richer PD data will provide the means to build more robust models.

PO-02-204 COLCHICINE USAGE FOR PREVENTION OF POST ATRIAL FIBRILLATION ABLATION PERICARDITIS IN PATIENTS UNDERGOING HIGH POWER SHORT DURATION ABLATION

Radiofrequency ablation (RFA) for atrial fibrillation (AF) can be associated with up to 10% incidence of post-operative pericarditis, suspected to be more prevalent with the advent of high-power short duration (HPSD) ablation. This has led to widespread use of colchicine, an anti-inflammatory medication, for prevention of post-AF ablation pericarditis. However, the utility of preventative colchicine remains unproven. To evaluate the efficacy of a routine post-operative colchicine regimen for prevention of post-ablation pericarditis in patients (pts) undergoing HPSD ablation for AF. We retrospectively evaluated consecutive single-operator HPSD AF ablation procedures at our institution from June 2019 to July 2022. A colchicine protocol was introduced in June 2021 for prevention of post-ablation pericarditis. None of the pts before this date received preventative colchicine while all consecutive pts after this date received routine colchicine 0.6 mg twice daily for 14 days starting on the procedure day. Pts were divided into colchicine and non-colchicine groups (gps). We recorded the incidence of post ablation chest pain, emergency room (ER) visit for chest pain, pericardial effusion, pericardiocentesis, any ER visit, hospitalization, AF recurrence and cardioversion (CV) for AF within the first 30 days post-ablation. We also recorded colchicine-related side effects and medication compliance. Out of 225 consecutive procedures, 20 were excluded for lack of follow-up data, yielding 101 pts in the colchicine gp and 104 pts in the non-colchicine gp. Both gps were well-matched for demographic and procedural parameters (Table 1). There was no significant difference in post-ablation chest pain (9.9% vs 8.6%, p = 0.7), pericardial effusion (2.9% vs 0.9%, p = 0.1), ER visits (11.9% vs 12.5%, p = 0.2), 30-day hospitalization for AF recurrence (0.9% vs 0.96%,p = 0.3) and 30-day need for CV for AF (3.9 % vs 5.7%, p = 0.2) (Table 1). 15 pts had severe colchicine-related diarrhea, out of which 12 discontinued it prematurely (Figure 1). In this single-operator retrospective analysis, preventative colchicine was not associated with any significant reduction in the incidence of pericarditis, pericardial effusion, ER visits or AF recurrence within the first 30 days after HPSD ablation for AF. Colchicine usage was associated with significant diarrhea affecting patient compliance. Our findings argue against routine use of colchicine for prevention of post AF-ablation pericarditis.

The Effect of Adding Curcumin to Sertraline in the Treatment of Severe Major Depressive Disorder: A Randomized, Double-Blind Clinical Trial.

Major depressive disorder (MDD) is a chronic and debilitating disease influenced by inflammatory processes in the brain. Some evidence has represented the adding curcumin as a complementary regime to the standard medication in treating depressive symptoms. However, limited clinical trials have been conducted on the antidepressants effects of curcumin in MDD patients. Therefore, this study aimed to investigate the effectiveness of curcumin in the treatment of MDD. In a randomized, double-blind clinical trial, 45 severe MDD patients referred to the psychiatric clinic of Ibn-e-Sina Hospital, Mashhad, Iran, during 2016 were selected. Patients were randomly divided into 2 groups who received sertraline plus curcumin or placebo at a dose of 40 mg/d for 8 weeks. The patients were evaluated using Beck Anxiety and Depression Surveys at the beginning of the study, fourth, and eighth weeks by a psychiatry resident. The data analyzed aiding SPSS software. While depression and anxiety significantly decreased during the 8 weeks of the study, there was no significant difference between the 2 groups (P > 0.05). However, the anxiety score was lower in the intervention group. Moreover, no severe adverse events were observed in all patients. Adding 40 mg/d of SinaCurcumin to sertraline as a routine medical regimen did not improve the depression and anxiety levels in severe MDD patients. However, the anxiety score was lower in the intervention group than in the placebo receiver, which suggests curcumin may have a more effect on anxiety.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Efficacy of topical galbanum oil with dry cupping in hospitalized COVID-19 patients: A randomized open-label clinical trial.

This study was designed to detect the therapeutic effects of galbanum oil plus dry cupping (a Persian medicine-based method) in hospitalized patients with coronavirus disease-2019 (COVID-19). In this randomized controlled trial, 60 hospitalized COVID-19 patients with positive polymerase chain reaction test (PCR), pulmonary involvement and blood oxygen saturation (SpO2) ≤93 mmHg, were randomly assigned into two groups to take the standard therapeutic regimen alone or alongside cupping and topical galbanum oil (Ferula gommosa oleo-gum resin) for 3-5 days. The SpO2 level, the severity of signs and symptoms of patients and laboratory parameters were compared between the two groups. Fifty-eight patients were analyzed. The SpO2 level changed from 89.27±3.82 to 90.29±3.09 mmHg (p=0.038) in control group, while it increased from 88.74±3.45 to 94.23±2.1 mmHg (<0.001) in galbanum group with a significant difference between the groups (p<0.001). Fever, cough, dyspnea, and anorexia alleviated in the galbanum group more than the control (p=0.003, 0.001, 0.01, and 0.04, respectively). No adverse effects were reported due to galbanum oil and cupping therapy. Dry cupping with galbanum oil alongside the routine therapeutic regimen could be more effective than the routine therapeutic regimen alone for improving SpO2 level and alleviating fever, cough, and dyspnea in COVID-19 patients.

Study on the Effect of Bushen Zhuanggu Tablet Combined with Conventional Regimen on Bone Mineral Density Improvement, Functional Recovery and Fracture Risk Prevention in Patients with Postmenopausal Osteoporosis.

This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of β-cross-linked C-terminal telopeptide of type I collagen (β-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.