Incidence Of Side Effects Research Articles

Advances in epidural labor analgesia: Effectiveness and treatment strategies of butorphanol

In this editorial, we provide a critical review of the article by Tang et al published in the World J Clin Cases , focusing on the utilization of butorphanol for epidural analgesia during labor. Our discussion encompasses recent research developments in epidural labor analgesia, specifically highlighting the current status of clinical applications of butorphanol and associated treatment approaches. Epidural analgesia is widely acknowledged as the primary method for pain management during labor, offering effective and prolonged pain relief while allowing mothers to remain alert and actively participate in the delivery process. Among the various drugs utilized for epidural labor analgesia, butorphanol has received increasing attention due to its potential efficacy and distinctive pharmacological properties. As a synthetic opioid analgesic, butorphanol exhibits both agonistic and antagonistic activity on opioid receptors, striking a balance between analgesia and minimizing side effects. Nevertheless, the safety and efficacy of butorphanol in epidural labor analgesia remains controversial. While certain studies have reported positive outcomes with butorphanol, including effective pain relief and a reduced incidence of side effects, others have raised concerns about its safety and efficacy compared to traditional opioids or alternative analgesics. In addition, the optimal dosing strategy and regimen of butorphanol as an adjuvant in epidural labor analgesia still need to be verified. Through comprehensive synthesis and analysis of existing literature, we aim to evaluate the current evidence regarding the use of butorphanol for epidural labor analgesia, delineate areas of consensus and controversy, and propose future avenues for research and clinical practice in this domain.

The potency-ratio of ciprofol and propofol under procedural sedation and anesthesia for outpatient hysteroscopy during cervical dilation: a study using up-and-down sequential allocation method.

Ciprofol(HSK3486) is a novel 2,6-disubstituted phenol derivate, a short-acting intravenous sedative, which has similar efficacy characteristics as propofol with less incidence of side effect. Both ciprofol and propofol are often used in outpatient hysteroscopic surgery for sedation. However, the relative potency of these two drugs has not been fully determined in this context. Our study aimed to investigate the potency-ratio of ciprofol and propofol under procedural sedation and anesthesia in restraining reaction of outpatient hysteroscopy dilatation. The ED50 (effective dose in 50% of subjects) value for ciprofol and propofol were calculated by Up-and-Down Sequential Allocation Method. 60 healthy patients undergoing daytime hysteroscopy were randomly divided into two groups, which were intravenously injected with ciprofol at an initial dose of 0.4mg/kg (group C) or propofol at an initial dose of 2mg/kg (group P) at 2min after intravenous injection of sufentanil 0.15ug/kg. A successful response is defined as the absence of patient movement in the case of cervical dilation. Conversely, the presence of patient movement is defined as failure. After successful or failed responses, each follow-up patient in the corresponding group was reduced or increased with propofol 0.5mg/kg or ciprofol 0.1mg/kg, respectively. The estimated ED50 value for ciprofol and propofol in restraining reaction of hysteroscopy dilatation was 0.444mg/kg (95% CI, 0.385-0.503mg/kg) and 1.985mg/kg (95% CI, 1.801-2.170mg/kg), respectively. The incidence of respiratory depression, hypoxemia and injection pain in ciprofol was significantly lower than those in propofol. The ED50 of ciprofol and propofol in preventing hysteroscopy dilatation reaction was 0.444mg/kg (95% CI, 0.385-0.503mg/kg) and 1.985mg/kg (95% CI, 1.801-2.170mg/kg) for outpatient hysteroscopy. The potency-ratio of ciprofol and propofol observed in our study was 1.0:4.5(95%CI,1:3.9-1:5.1). The study was registered at Chinese Clinical Trial Registry http//www.chictr.org.cn/ (Registration date19/11/22 Trial ID ChiCTR2200065954).

Clinical efficacy observation of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in treatment of malignant pleural effusion

To investigate the clinical efficacy of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in comparison with simple intrapleural perfusion of cisplatin on malignant pleural effusion (MPE). Forty patients with MPE, in compliance with the inclusion criteria, were randomly divided into an observation group (20 cases) and a control group (20 cases). In the control group, cisplatin solution (60 mg/m2) was injected into the thoracic cavity after pleural drainage under B-ultrasound positioning, once a week for 4 weeks. In the observation group, based on the intervention as the control group, the heat-sensitive moxibustion was delivered at the back and lumbar region (where Feishu ［BL13］, Pishu ［BL20］ and Shenshu ［BL23］ are located) and the chest-abdomen region (where Danzhong ［CV17］, Guanyuan ［CV4］ and Shuidao ［ST28］ are located), for 30 min to 90 min, once daily (the treatment was discontinued on Saturday and Sunday) and for 4 weeks. Before and after treatment, in the two groups, the pleural effusion volume was detected using B ultrasound, the activity of daily living was evaluated with Karnofsky performance statue (KPS) scale and TCM symptoms with TCM syndrome grading scale. The clinical therapeutic effect was evaluated in the two groups. According to the classification criteria table for acute and subacute toxicity of anticancer drugs made by WHO, the toxic and side reaction was judged. After treatment, the pleural effusion volume was reduced in comparison with that before treatment in the two groups (P<0.01, P<0.001), and the volume in the observation group was lower than that of the control group (P<0.05). KPS score was increased in the two groups after treatment compared with that before treatment (P<0.001), and the score in the observation group was higher than that of the control group (P<0.05). After treatment, the total score of TCM syndromes and the scores for dyspnea, cough and chest pain were lower than those before treatment in the two groups (P<0.001), and the scores in the observation group were lower than those of the control group (P<0.001, P<0.05). The scores for anorexia and lassitude were reduced in comparison with those before treatment in the observation group (P<0.001)；and the scores in the observation group were lower than those in the control group after treatment (P<0.001, P<0.01). After treatment, the effective rate of the observation group was 65.0%(13/20), which was higher than that of the control group (30.0%, 6/20, P<0.05). The incidence of bone marrow suppression in the observation group was 15.0%(3/20), lower than that in the control group (55.0%, 11/20, P<0.05). The incidence of gastrointestinal reactions in the observation group was 30.0%, lower than that in the control group (65.0%, 13/20, P<0.05). Heat-sensitive moxibustion combined with intrapleural infusion of cisplatin is superior to intrapleural infusion of cisplatin in the aspects of the amelioration of pleural effusion, daily-living activity and TCM syndromes in patients with MPE. This combined therapy presents the synergism by cooperating with chemotherapeutics and reduces the incidence of toxic and side effects implicated in chemotherapy so as to attenuate the toxicity of chemotherapeutics.

Incidence of side effects associated with acetaminophen in people aged 65 years or more: a prospective cohort study using data from the Clinical Practice Research Datalink.

The main objective of this study is to examine the safety of oral acetaminophen at its therapeutic dose in adults aged 65 years or more. This population-based cohort study used the Clinical Practice Research Datalink-Gold data. Participants were aged ≥65 years registered with a UK general practice for at least 12 months between 1998 and 2018. Acetaminophen exposure was defined as at-least two acetaminophen prescriptions within six-months of the first acetaminophen prescription, the first prescription date being the index-date. Acetaminophen non-exposure was defined as the absence of two acetaminophen prescriptions within six-months over the study period. We calculated propensity-score (PS) for acetaminophen prescription and undertook inverse probability treatment weighted (IPTW) using PS and PS-matched analyses to account for confounding. Missing data were handled using multiple imputation. The adjusted hazard-ratio (aHR) and 95% confidence-interval (CI) were calculated using the Cox-proportional hazards regression model. In total, 180,483 acetaminophen-users and 402,478 non-users were included in this study. Acetaminophen use was associated with an increased risk of peptic ulcer bleeding (aHR 1.24; 95% CI 1.16, 1.34), uncomplicated peptic-ulcers (aHR 1.20; 95% CI 1.10, 1.31), lower gastrointestinal-bleeding (aHR 1.36; 95% CI 1.29, 1.46), heart-failure (aHR 1.09; 95% CI 1.06, 1.13), hypertension (aHR 1.07; 95% CI 1.04, 1.11), and chronic kidney disease (aHR 1.19; 95% CI 1.13, 1.24). Despite its perceived safety, acetaminophen is associated with several serious complications. Given its minimal analgesic effectiveness, the use of acetaminophen as the first-line oral analgesic for long-term conditions in older people requires careful reconsideration.

Significant haematological alterations in clozapine-treated patients: prevalence and clinical correlation.

Clozapine is an atypical antipsychotic crucial for treatment-resistant schizophrenia, characterised by its multi-receptor targeting, including serotonin (5-HT2A, 5-HT2C) and dopamine (D1, D2, D3, D4) receptors, among others. This broad mechanism is effective against positive symptoms of schizophrenia with a lower incidence of extrapyramidal side effects. However, clozapine poses significant haematological risks, notably agranulocytosis, necessitating stringent blood monitoring protocols. This study examined haematological parameters in 157 patients on clozapine therapy, analysing the prevalence and clinical correlations of haematological abnormalities such as leucocytosis, thrombocytosis, and alterations in red blood cell distribution width (RDW) and mean platelet volume (MPV). The findings revealed leucocytosis in 36.9% of patients, thrombocytosis in 8.9%, and elevated RDW in 23.6%. Notably, higher clozapine doses were associated with leucocytosis, though no significant correlations were found between clozapine dose, duration of use, and changes in RDW, mean corpuscular haemoglobin concentration, or MPV. The study's results underscore the necessity of regular haematological monitoring to mitigate the risks of clozapine therapy while leveraging its therapeutic benefits. Additionally, the study suggests personalised dosing strategies to balance efficacy and safety, particularly in managing clozapine-induced haematological changes.

225Ac]Ac‐PSMA for the treatment of metastatic castration‐resistant prostate cancer: A systematic review and meta‐analysis

AbstractBackgroundApproximately 10%–20% of prostate cancers progress to metastatic and castration‐resistant forms (mCRPC). Radioligand (RLT) therapy with [177Lu]Lu‐prostate‐specific membrane antigen (PSMA) is an approved treatment for metastasized mCRPC. Moreover, Actinium‐225 (225Ac), an alpha‐emitter isotope, has also been used to label PSMA and, recently, to treat mCRPC patients with encouraging results. However, robust clinical data on [225Ac]Ac‐PSMA therapy and its comparison with [177Lu]Lu‐PSMA are still limited. Our aim was to evaluate the role of [225Ac]Ac‐PSMA in treating mCRPC and compare it with conventional [177Lu]Lu‐PSMA therapy.MethodsA systematic search was performed in PubMed, Web of Science, Scopus and the Cochrane Register of Controlled Trials from June 2023 to January 2024. This work was conducted in accordance with PRISMA guidelines.ResultsAfter screening and study selection according to PRISMA guidelines, 11 studies were included, 9 of which focused on [225Ac]Ac‐PSMA only and two on tandem therapy ([225Ac]Ac‐PSMA/[177Lu]Lu‐PSMA). Overall, the pooled proportion of PSA decline in patients was .85 (95% CI: .79–.91, p &lt; .001); patients pretreated with [177Lu]Lu‐PSMA achieved a pooled proportion of PSA decline of .90 (95% CI: .82–.97, p &lt; .001). In patients treated with tandem therapy, PSA decline was observed in approximately 90% of them, while PSA response rates above 50% ranged from 53.3% to 65%. Xerostomia was the most frequently reported side effect, along with anaemia, thrombocytopenia and nephrotoxicity.ConclusionsOverall, the main results of our study showed that [225Ac]Ac‐PSMA‐617 had a significant therapeutic effect on mCRPC with an acceptable toxicity level. The latter, however, appears greater than with [177Lu]Lu‐PSMA‐617. In future studies, an adequate analysis of the incidence of side effects associated with [225Ac]Ac‐PSMA should be performed to evaluate the role of cumulative toxicity of earlier treatments and the higher frailty of heavily pretreated patients.

USO DO RETINOL NO TRATAMENTO DO ENVELHECIMENTO

INTRODUCTION: Skin aging results from intrinsic and extrinsic processes, manifesting itself in characteristics such as wrinkles and loss of firmness. Retinol, a form of vitamin A, plays a crucial role in skin health but can cause irritation, limiting skin acceptance. This study investigates the benefits of retinol in treating aging, including its effectiveness, dosage forms and interactions with other substances. METHODOLOGY: A systematic search was conducted, in accordance with PRISMA guidelines, using the PubMed and VHL databases until August 2024. The search was based on descriptors in English, such as “Retinol AND AntiAging”, applying exclusion criteria to limit the scope to relevant studies. RESULTS AND DISCUSSION: The search identified 128 studies, of which 13 met the eligibility criteria. Topical application of retinol has been shown to be effective in modulating the molecular biology of the skin, with a lower incidence of side effects compared to more potent retinoids. Studies have also indicated that combining retinol with massage techniques and new formulations, such as cyclodextrin encapsulation, improves its effectiveness and reduces irritation. Additionally, interactions with substances such as niacinamide and bakuchiol enhance anti-aging results. CONCLUSION: Topical use of retinol is a safe and effective approach to skin aging, offering significant benefits and reduced irritation. Its combinations with other substances and modern technologies promise innovative solutions for skin care.

Characteristics of Side Effects in Non-Emergency Indications Using Computer-Controlled Pressurized Monoplace Hyperbaric Chambers: A Retrospective Multicenter Study.

Background: Hyperbaric oxygen therapy (HBOT) involves inhaling nearly 100% oxygen in a pressurized environment and is commonly used to treat various diseases and injuries. Despite its well-known safety, HBOT is associated with side effects, with frequent middle ear barotrauma (MEB) and oxygen toxicity. Understanding the characteristics and risk factors associated with these side effects is critical for improving patient compliance and treatment outcomes. Methods: This retrospective multicenter study aimed to analyze the characteristics and factors associated with side effects during HBOT using a computer-controlled pressurized monoplace hyperbaric chamber. We conducted a retrospective observational study across the two tertiary hospitals in Korea, involving patients who received HBOT from October 2016 for one hospital and October 2017 for another hospital to June 2020. Data were extracted from electronic medical records and hyperbaric chamber logs, including patient demographics, medical history, HBOT indications, and details of side effects. Statistical analyses, including chi-square and t-tests, were used to compare variables. Results: A total of 247 patients (mean age: 59.35 ± 15.05 years, 63.56% male) were included. The most common indications for HBOT were sudden sensorineural hearing loss (27.94%) and post-graft/flap (24.29%). Hypertension (46.15%) and diabetes mellitus (39.27%) were the most frequent comorbidities. Otalgia was the most prevalent side effect (33.20%), followed by chest discomfort (2.02%) and headache (1.62%). A significant proportion of patients (11.74%) terminated HBOT due to side effects, with most pauses occurring at pressures between 1.2 and 1.4 ATA (26.67%). Side effects, particularly otalgia, significantly impact patient compliance with HBOT. Conclusions: The incidence of side effects varies by pressure level during treatment, suggesting the need for tailored strategies to minimize side effects. This study highlights the importance of patient monitoring and education to improve the safety and efficacy of HBOT in monoplace chambers.

Promising role of Voxelotor in managing sickle cell disease in children: a narrative review.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and intermittent vaso-occlusive crises. To date, four disease-modifying drugs have been approved for the treatment of SCD: hydroxyurea (an S-phase inhibitor), L-glutamine (an amino acid), crizanlizumab (a P-selectin inhibitor), and voxelotor (a hemoglobin S polymerization inhibitor). Preclinical studies suggested that voxelotor effectively treats SCD and sickle cell anemia (SCA). In a phase III trial, voxelotor-treated patients showed significantly elevated hemoglobin levels (>1 g/dL from baseline) compared to placebo-treated patients. The group that received voxelotor also showed a greater decrease in hemolytic markers but a comparable incidence of side effects. Six ongoing clinical trials also sought to ascertain the effectiveness and safety of high-dose voxelotor when administered to children younger than 12 years. Studies assessing their long-term efficacy and safety are needed to fully understand the role of voxelotor in treating SCD/SCA. In this review, we discuss the mechanisms, trials to date, and future treatment directions of voxelotor.

Comparison of ultrasound-guided fascia iliaca compartment block versus the combined obturator nerve and adductor canal block application in postoperative analgesia for patients undergoing arthroscopic knee surgery

Background: Arthroscopic knee surgery is a surgical intervention that is frequently performed by orthopedic clinics and new studies are constantly carried out by anesthetists to ensure effective pain control. This study aimed to compare the efficacy of ultrasound-guided suprainguinal fascia iliaca compartment block (FICB) versus the combined adductor canal and obturator nerve block application in terms of postoperative analgesia in patients undergoing arthroscopic knee surgery under spinal anesthesia.Materials and Method: Sixty patients, who underwent arthroscopic knee surgery under elective conditions were included in the study. They were randomly divided into two groups, Group 1 (n=30) and Group 2 (n=30), using a lottery method. Patients operated under spinal anesthesia received ultrasound-guided suprainguinal fascia iliaca compartment block (FICB) for Group 1. The combined adductor canal and obturator nerve block for Group 2 at the end of the surgery. Intravenous patient-controlled analgesia (PCA) device containing tramadol was connected to all patients in both groups, and they were evaluated for Visual Analog Scale (VAS) scores at 0, 2, 4, 12, and 24 hours of ward follow-up. The amount of PCA used at 24 hours, additional analgesic use, development of side effects, mobilization capabilities, and satisfaction levels were assessed at the end of 24 hours.Results: There were no significant differences between the groups in terms of demographic characteristics and the type of surgery performed (p&gt;0.05). In Group 1, where fascia iliaca block was applied the block administration time was observed to be significantly shorter compared to Group 2 (p&lt;0.05). No significant differences were observed between the two groups in terms of postoperative VAS scores, PCA usage amounts, incidence of side effects, postoperative mobilization abilities, and satisfaction measures (p&gt;0.05).Conclusions: Ultrasound-guided fascia iliaca compartment block alone can be effectively applied for postoperative analgesia in patients undergoing arthroscopic knee surgery, instead of combined adductor canal and obturator nerve block.

Spotlight on Amniotic Membrane Extract Eye Drops: A Review of the Literature.

To review the literature focusing on the effectiveness of amniotic membrane extract eye drops (AMEDs) in the treatment of ocular surface diseases. PubMed/MEDLINE, Scopus, and CENTRAL databases were searched until March 4, 2024. Overall, we identified 1,121 studies, 26 of which were selected for a full-text review. Twelve studies met the inclusion criteria and were analyzed for clinical improvements, time to resolution of corneal staining, adverse events, and preparation methods. Strength of clinical data was graded according to the Oxford Center for Evidence-Based Medicine. Overall, AMED compounds were used in 296 eyes of 205 patients. Fifty-nine percent of eyes were treated for dry eye disease, 23% for an epithelial defect, and the rest (18%) for other corneal wound healing disorders. Three main types of eye drops preparation were described, that is, lyophilized, homogenized, and fresh AMED. Although the methods of outcome reporting were heterogeneous, all included studies showed various grades of improvement in both signs and symptoms. The overall incidence of ocular side effects was 2.3%. Despite the suboptimal quality of evidence, overall, the available literature suggests that AMED is a valuable tool in the treatment of ocular surface disorders.

Effect of Valproate Coprescription on Clozapine Pharmacokinetics in Clinical Practice

Abstract Background Sodium valproate has been coprescribed with clozapine for seizure prophylaxis and for augmentation in treatment-refractory schizophrenia. However, the effect of valproate on clozapine metabolism and on the incidence of clozapine-related side effects is unclear. Methods We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in smokers and nonsmokers of both sexes in samples submitted for clozapine therapeutic drug monitoring, 1996–2017 in relation to valproate coprescription. Results There were 1217 (665 patients) and 3823 (1600 patients) samples from nonsmokers and from smokers, respectively, who were coprescribed valproate and clozapine. Data from 9774 (5065 patients) and 15,465 (7298 patients) samples from nonsmokers and from smokers, respectively, for whom drugs other than valproate were coprescribed were used as controls. Valproate coprescription in nonsmokers was associated with an increase in average plasma clozapine of 22.5%, suggesting moderate inhibition of clozapine metabolism, but there was no marked effect of valproate coprescription on plasma clozapine in smokers. In all the valproate-treated groups (male and female smokers and nonsmokers), the median plasma norclozapine concentration and the median plasma clozapine-to-norclozapine ratio were significantly lower and higher, respectively, as compared with the controls. Mixed-effects models showed a significant dose-response effect of valproate on lowering the plasma norclozapine concentration and on increasing the plasma clozapine-to-norclozapine ratio. Implications Given the complexity of the effect of valproate coadministration on clozapine pharmacokinetics and the possibility that the toxicity of clozapine may be enhanced in the presence of valproate, the use of these drugs in combination must now be questioned in all patients and not only in women of childbearing age.

COMPARISON OF TWO DIFFERENT DOSES OF ORAL GABAPENTIN FOR POST OPERATIVE ANALGESIA IN LOWER LIMB SURGERY UNDER SPINAL ANAESTHESIA

Background: Pre-emptive analgesia is a technique of pain control where treatment is initiated before intervention and operational during the surgical procedure in order to reduce the physiological consequences of nociceptive transmission provoked by the procedure. Gabapentin has demonstrated analgesic effects in clinical trials as a preemptive analgesic in acute postoperative pain management with very few side effects. Owing to the protective effect of gabapentin on the nociceptive pathways, preemptive analgesia has the potential to be more effective and hence reduce postoperative pain and development of chronic pain. Objective: We therefore designed this study to compare two different doses of Oral Gabapentin (300mg and 600mg) given as pre-emptive analgesic for post-operative pain relief in lower limb surgeries under spinal anaesthesia. Method: After the approval from ethical committee this prospective randomized double blinded clinical study was conducted over a period of two years in department of anaesthesia in M.G.M.s medical college, Aurangabad. Randomly allocated two groups were given Oral Gabapentin 300mg and 600mg respectively, one hour prior to giving spinal anaesthesia for post operative analgesia in lower limb surgeries. Conclusion: There is no statistically significant difference between group G300 (gabapentin 300mg) and group G600 (gabapentin 600mg) regarding age, gender, duration of analgesia (i.e. demand for first rescue analgesic), total dose of analgesics in first twenty four hours after surgery, duration of sensory block (i.e. L1 regression), highest ramsay sedation score and VAS scores. No significant difference was seen in cases hemodynamic stability and incidence of side effects.

СОВРЕМЕННОЕ ЛЕЧЕНИЕ РУБЦОВОЙ ДЕФОРМАЦИИ ТКАНЕЙ

The problem of scar treatment is one of the most widespread in modern medicine. Treatment of scar formations is one of the most difficult tasks, as there is no single standard that is favorable in terms of efficacy and safety despite the active development in this area of research. Currently, conservative methods of treatment of scar tissue deformities such as corticosteroid administration, botulinum therapy, cryotherapy, microneedling, as well as surgical excision in combination with therapeutic methods are widely used, due to which the most favorable result is achieved. This study is devoted to the study of various modern methods of correction of hypertrophic and keloid scars that are becoming widespread in medicine, their comparison and identification of important advantages and disadvantages in order to choose the most effective treatment technique. Currently used conservative methods of treatment allow to cope with the problem of scar formations, but due to the high incidence of side effects, there is a tendency to search for the combined use of each of them, including with surgical excision to prevent the development of recurrences and to achieve a pronounced cosmetic effect and satisfaction among patients. Thanks to the constant development of medicine and the improvement of various methods, each patient can receive a personalized treatment approach that is guaranteed to reduce aesthetic discomfort due to the existing pathology, which is the main and important aspect of scar correction.

Comparative study between the roles of intrauterine misoprostol versus the sublingual route for prevention of postpartum blood loss in elective cesarean sections: a randomized controlled trial

BackgroundThe prostaglandin E1 analog “misoprostol” is a drug that has powerful ecbolic effects and can be beneficial in the prevention and treatment of postpartum hemorrhage, which is the leading cause of maternal mortality worldwide.ObjectivesTo assess the value of adding intrauterine misoprostol together with intravenous oxytocin injection compared with sublingual misoprostol together with intravenous oxytocin injection during elective cesarean section to reduce blood loss intraoperatively and prevent postpartum hemorrhage.MethodsA total of 192 pregnant women were counseled and recruited from the labor and delivery unit at Kasr Al Aini Hospital, Cairo University, and equally randomized into two groups. Group (A) included 96 women who received intrauterine misoprostol (400 mg) + oxytocin. Group (B) included 96 women who received sublingual misoprostol (400 mg) + oxytocin. The primary outcome of our study was estimation of the amount of blood loss during and after cesarean delivery. The secondary outcomes were the incidence of PPH within the first 6 h after labor, the need for blood transfusion, the need for any supplementary ecbolic drugs, the need for additional surgical intervention for PPH, changes in hematocrit and hemoglobin in both groups after delivery, and the incidence of side effects of the study medications.ResultsWe observed a significant discrepancy between the two groups in terms of postoperative Hb and Hct, postoperative differences (pre- and post-Hb and post-Hct) and EBL favoring the intrauterine group. However, no significant difference was observed between the groups with respect to excessive blood loss > 1000 ml in the 1st six hours, the need for supplementary ecbolics, the necessity for blood or blood prod, the need for additional surgical intervention (for PPH) or side effects.ConclusionIntrauterine misoprostol combined with oxytocin intravenous infusion is more effective than sublingual misoprostol combined with oxytocin intravenous infusion in lowering intraoperative blood loss and preventing postpartum hemorrhage in elective cesarean section.Trial registrationThis trial was retrospectively registered with the ClinicalTrials.gov Registry on 12-April-2024 (registration number: NCT06364098).

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis &amp;lt; 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

A network meta-analysis of different acupuncture therapy in the treatment of poststroke cognitive impairment and dementia.

Poststroke cognitive impairment and dementia (PSCID) is a major cause of stroke-related morbidities and mortalities. Over the last few years, there has been growing evidence supporting the effectiveness of needle-related treatments in PSCID. Our goal was to rate the included therapies and assess the clinical effectiveness of various needle-related treatments in patients with PSCID. We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, FDA.gov, and ClinicalTrials.gov. A mix of subject terms and free words was used to search the databases. The retrieval period was from the inception date of the database to February, 2023. We included SRs and MAs from acupuncture RCTs of patients with PSCID. The Cochrane Risk Assessment Scale was used to evaluate the risk of bias in the included studies. State 17.0 was used for network meta-analysis in accordance with the Bayesian framework. There were 34 studies total of 2690 patients. The cumulative ranking curve (SUCRA) revealed that CT + CFT + EA was the most efficient intervention to improve (Mini-Mental State Examination, MMSE) efficiency, followed by CT + CFT + AP to improve (Montreal Cognitive Assessment, MoCA) efficiency, CT + CFT + ACU for improving (Activities of Daily Living scale, ADL) scores, and CT + CFT + EA to improve clinical efficiency. The results show that Different acupuncture methods can improve cognitive function and daily living ability in patients with PSCID. Network meta-analysis revealed that both CT + CFT + ACU and CT + CFT + EA appeared to be more beneficial for daily living activities, while CT + CFT + EA and CT + CFT + AP appeared to be more helpful for cognitive performance in patients with PSCID. Treatments including acupuncture are safer and have a reduced incidence of negative side effects.

The Analgesic and Side Effects of Tramadol Hydrochloride Immediate-Release and Extended-Release Tablets in Patients With Chronic Low Back Pain.

There are no established treatments for low back pain. Conventional treatments includephysiotherapyand pharmacological treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs). Recently, analgesics with mechanisms of action different from those of NSAIDs have emerged. Tramadol formulations have especially attracted attention for being effective among patients in whom NSAIDs are not entirely effective. However, they are associated with side effects that can disrupt treatment. Tramadol hydrochloride immediate-release and extended-release tablets havebeen recently launched. Herein, we report our experience with these formulations in chronic low back pain patients. To investigate the incidence of side effects and the analgesic effect of tramadol hydrochloride immediate-release and extended-release tablets in patients with chronic low back pain. This was a multicenter retrospective observational study. The study included patients prescribed tramadol hydrochloride immediate-release and extended-release tablets for chronic low back pain at 13 facilities in Japan between January 2021 and December 2023. The primary outcome was the incidence of side effects observed during the study period. The secondary outcomes were changes in the visual analog scale (VAS) score. The incidence of side effects was 37.7% (40/106 cases), which included constipation, nausea, drowsiness, and dizziness in 23 (21.7%), 13 (12.3%), 4 (3.8%), and 2 (1.9%) cases, respectively. The rate of treatment discontinuation owing to side effects was relatively low (16/106 cases, 15.1%). Furthermore, after four weeks of treatment, we found a significant reduction in the VAS scores for low back pain from baseline. This study shows the incidence of side effects following the administration of tramadol hydrochloride immediate-release and extended-release tablets. Regarding the breakdown of side effects, constipation, nausea, drowsiness, and dizzinesswere noted. Regarding pain evaluation, we found a significant reduction in the VAS scores for low back pain from baseline after four weeks of treatment, suggesting that tramadol hydrochloride immediate-release and extended-release tablets may provide excellent analgesic effects owing to their pharmacokinetic properties that ensure stable tramadol concentrations in the bloodstream.

Thermosensitive hyaluronic acid-manganese-capsaicin complex nanogel improving NKG2D/CAR-T melanoma treatment through adjusting tumor microenvironment

Intratumorally injection of CAR-T cells to treat melanoma can reduce the incidence of systemic side effects and ensure an adequate concentration of CAR-T cells. However, few targeting ligands and hostile tumor microenvironment (TME) inhibit the CAR-T cells' survival and infiltration. An in situ hyaluronic acid‑manganese-capsaicin complex nanogel (HA-Mn-CAP Gel) was designed by forming complex nanogel based on the main skeleton material of hyaluronic acid (HA). It targeted CD44 and TRPV1 receptors through HA and CAP, concentrated and released Mn at melanoma, subsequently relieving the hypoxia in the tumor and increasing the expression of CAR-T cells' specific ligands. Cell experiments showed that HA-Mn-CAP Gel significantly enhanced the expression of representative NKG2D ligands (MICA/B and ULBP2/5/6) >2.7 times on A375 melanoma cells. Sequential administration of HA-Mn-CAP Gel and NKG2D/CAR-T increased the tumor inhibition rate about 1.5 times that of the NKG2D/CAR-T group in melanoma-bearing NSG mice. The results of immunohistochemistry and immunofluorescence assays showed that the combined HA-Mn-CAP Gel and NKG2D/CAR-T significantly increased the proliferation and infiltration of T cells, especially for CD8+ cells. Therefore, the new promising strategy of increasing the target ligand expression and adjusting TME before administering CAR-T cells is suitable for treating solid tumors.

Assessment of basic pharmacokinetic parameters of dapagliflozin in TTS formulations in male minipigs

Given the extended time over which diabetes treatment is administered, the transdermal delivery system is anticipated to be a more suitable option for older individuals who may experience difficulty swallowing. The continuous delivery of dapagliflozin and more stable plasma levels are anticipated to reduce the incidence of side effects and the frequency of dosing. The objectives of the study were to determine the safety and plasma pharmacokinetics of dapagliflozin in male minipigs following application of the ointment and skin patch. In the initial phase of the study, the potential for transdermal permeation of dapagliflozin from ointment and transdermal patch to blood plasma of 15 male Göttingen minipigs was investigated. In the subsequent phase, the efficacy of utilising patches of varying strengths and sizes was assessed. The LC/MS method was employed to quantify the concentration of the active substance. The transportation of the studied API to the general circulation and accumulation in tissues were confirmed. The maximum drug concentration (122.99 ng/mL) in plasma was observed on the fourth day of application. The highest calculated Cmax was 131.91 ng/mL with a mean AUC0-last of 6620.7 ng h/mL. Following transdermal administration, dapagliflozin is excreted in the urine. The trend between urinary dapagliflozin 3-O-glucuronide levels and urinary glucose excretion was also observed. The transdermal patch has been demonstrated to be an effective drug delivery system for dapagliflozin.