Incidence Of Other Adverse Reactions Research Articles

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Olanzapine for the treatment of ICU delirium: a systematic review and meta-analysis.

As an atypical antipsychotic drug, olanzapine is one of the most commonly used drugs for delirium control. There are no systematic evaluations or meta-analyses of the efficacy and safety of olanzapine for delirium control in critically ill adults. In this meta-analysis, we evaluated the efficacy and safety of olanzapine for delirium control in critically ill adults in the intensive care unit (ICU). From inception to October 2022, 12 electronic databases were searched. We retrieved randomized controlled trials (RCTs) and retrospective cohort studies of critically ill adults with delirium that compared the effects of olanzapine and other interventions, including routine care (no intervention), nonpharmaceutical interventions and pharmaceutical interventions. The main outcome measures were the (a) relief of delirium symptoms and (b) a decrease in delirium duration. Secondary outcomes were ICU and in-hospital mortality, ICU and hospital length of stay, incidence of adverse events, cognitive function, sleep quality, quality of life, mechanical ventilation time, endotracheal intubation rate and delirium recurrence rate. We applied a random effects model. Data from 10 studies (four RCTs and six retrospective cohort studies) involving 7076 patients (2459 in the olanzapine group and 4617 in the control group) were included. Olanzapine did not effectively relieve delirium symptoms (OR = 1.36, 95% CI [0.83, 2.28], p = 0.21), nor did it shorten the duration of delirium [standardized mean difference (SMD) = 0.02, 95% CI [-1.04, 1.09], p = 0.97] when compared with other interventions. Pooled data from three studies showed that the use of olanzapine reduced the incidence of hypotension (OR = 0.44, 95% CI [0.20, 0.95], p = 0.04) compared with other pharmaceuticals. There was no significant difference in other secondary outcomes, including ICU or hospital length of stay, in-hospital mortality, extrapyramidal reactions, QTc interval prolongation, or overall incidence of other adverse reactions. The number of included studies was not sufficient for performing a comparison between olanzapine and no intervention. Compared with other interventions, olanzapine has no advantage in alleviating delirium symptoms and shortening delirium duration in critically ill adults. However, there is some evidence that the rate of hypotension was lower in patients who received olanzapine than in those who received other pharmaceutical interventions. There was a nonsignificant difference in the length of ICU or hospital stay, in-hospital mortality, and other adverse reactions. This study provides reference data for delirium research and clinical drug intervention strategies in critically ill adults. Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42021277232).

Pharmacotherapy of gout – modern approaches and prospects

The article discusses modern approaches to the gout treatment, presented in foreign and domestic clinical guidelines. While the use of urate-lowering therapy for gout is a necessary and highly effective strategy, in the case of asymptomatic hyperuricemia, the benefits of this approach are not clear. The safety and efficacy of colchicine, as well as its cardioprotective properties, were noted in comorbid patients suffering from gout and cardiovascular diseases. Comparative data on safety and efficacy of the main urate-lowering drugs, allopurinol and febuxostat, are presented. It has been shown that, according to recent studies, febuxostat is more effective than allopurinol in normalizing serum uric acid levels, is not inferior in its cardio safety and is characterized by a lower incidence of other adverse reactions.

Efficacy and Side Effects in HER2-Positive Advanced Breast Cancer Patients Treated with Pyrrotinib: A Real-World Study in China

Background: Pyrotinib is a molecular and irreversible tyrosine kinase inhibitor independently developed in China, and its efficacy against HER2- positive breast cancer in the real world is not clear. In this study, we evaluated the efficacy and safety of pyrotinib in the treatment of HER2-positive advanced breast cancer based on real-world evidence. Materials and Methods: We designed a prospective observational study. Thirty-six patients with HER2-positive advanced breast cancer from a single medical center were included in the study from December 2018 to February 2021. All patients received the oral HER2 receptor inhibitor pyrotinib and received concurrent chemotherapy or endocrinotherapy. The follow-up endpoint is set as April 1, 2021. The primary endpoint is Objective Response Rate (ORR) and Disease Control Rate (DCR), and the secondary endpoint is Progression- Free Survival (PFS) and related side effects. Results: By the end point of follow-up, a total of 17 patients had progressed (including 6 deaths), and the progression-free survival rate was 52.78%. The median PFS was 13months (PFS range: 3-22 months). As the best response, 4 patients achieved CR, 20 patients achieved PR, 9 patients achieved SD, and 3 patient developed PD. The ORR was 66.67% and DCR was 91.67%. In the analysis, first-line pyrotinib treatment appeared to have higher ORR (88.88% vs 59.26%), but there was no significant difference. In addition, pyrotinib showed significant efficacy in patients with brain metastases, with an ORR of 42.85%. In terms of safety, the incidence of diarrhea was 80.55%, but only 4 patients had grade 3 diarrhea, which was tolerable after the drug dose was reduced; 1 patient had grade 4 neutropenia and grade 3 and thrombocytopenia, which were considered to be related to the chemotherapy drugs. The incidence of other adverse reactions was low, and all were grade 1 to 2. Conclusion: Pyrotinib combined with chemotherapy has a significant effect on HER2-positive breast cancer, and there is still a high ORR in patients who fail multiple lines of treatment. Side effects are overall controllable and safe.

Clinical Effect of Small-Dose Dexmedetomidine Combined with Oxycodone for Patient-Controlled Analgesia After Colon Cancer Surgery

This study aimed to elucidate the efficacy and safety of oxycodone combined with dexmedetomidine for patientcontrolled analgesia after colon cancer. Sixty patients were randomly divided into the experimental and control groups (n = 30 each). The control group received 0.5 mg/kg oxycodone. The experimental group received 0.5 mg/kg oxycodone and 2 μg/kg dexmedetomidine. Both groups were administered normal saline (NS) up to 100 mL (via background infusion at 2 mL/h with a 0.5-mL bolus dose and 15-min lockout interval). Both groups received oxycodone 0.1 mg/kg and tropisetron 5 mg, 20 min before the end of surgery. The MAP and HR of T1, T2, T3, and T4 were recorded in three groups. After the operation, a blinded observer assessed pain using the visual analogue scale (VAS) score, level of sedation (Ramsay score), and postoperative nausea and vomiting score at 2, 6, 24, 48 h. Side effects included dizziness, shivering, headache, and pruritus. The results showed that, in the experimental group, the T2∼T5 activity pain and T2∼T4 visceral pain VAS scores of patients were obviously lower than those in the control group (activity pain P T2∼T5 = 0.000, visceral pain P T2 = 0.018, P T3 = 0.001, P T4 = 0.010). The dosage of analgesic pump and number of rescue analgesia occurrences in the experimental group were far lower than those in the control group (P = 0.000 and P = 0.029, respectively). The time of first anus exhaust of the patients in the experimental group was obviously earlier than that of the control group (P = 0.030), and the number of vomiting occurrences of the patients in the experiment group was obviously lower than that in the control group (P = 0.023). No significant differences in the incidence of other adverse reactions were observed between the two groups within 48 h post-operation (P &gt;0.05). In summary, oxycodone combined with dexmedetomidine can be safely and effectively used for analgesia after laparoscopic radical resection of colon cancer.

Penehyclidine hydrochloride on postoperatively cognitive function

There are many drugs that affect postoperative cognitive function in patients under general anesthesia. Pentanethaquine hydrochloride (PHC), as a new type of anti-cholinergic drug, has been widely used. In clinical practice, many patients, especially elderly patients, have suffered from obvious postoperative cognitive dysfunction, but the incidence of pulmonary infection, reduced probably due to the decease of secretion production. Therefore, the effect of PHC on postoperative cognitive functions and inflammatory factors in elderly lung cancer patients under general anesthesia were mainly discussed to determine the clinical advantages and disadvantages. Ninety elderly patients undergoing thoracoscopic surgery for lung cancer under general anesthesia were selected and divided into PHC group (group A, n = 30), atropine group (group B, n = 30) and normal saline control group (group C, n = 30). The incidence of postoperative blurred vision was higher in group A compared to group B and C (both p < 0.05). The incidence of other adverse reactions was higher in group A compared to group C (all p < 0.05), but there was no difference between group A and group B (all p > 0.05). There was no significant difference in preoperative and day 1 post-surgery mini-mental state examination (MMSE) scores among the three groups (both p > 0.05), but the day 1 post-surgery MMSE scores of three groups were lower (all p < 0.05). PHC increased the incidence of postoperative cognitive impairment and postoperative delirium in elderly lung cancer patients undergoing thoracoscopic surgery under general anesthesia, but reduced the incidence of postoperative pulmonary complications possibly by reducing the expression of pro-inflammatory cytokines.

Application via mechanical dropper alleviates sufentanil-induced cough: a prospective, randomized, single-blinded trial

BackgroundIt was reported that prolonging the injection time or diluting administration can reduce the incidence of opioid-induced cough. However, the incidence of sufentanil-induced cough (SIC) via a standardized infusion rate is unclear. A mechanical dropper is an infusion filtering device commonly used for intravenous degassing; it can also be used to administer special drugs due to its temporary storage and dilution effect. This study assesses the effectiveness of administration via mechanical dropper on SIC.MethodsTwo hundred patients undergoing general anesthesia were enrolled. Patients received sufentanil at a strength of 0.3 μg·kg− 1 either via T-connector (group C) or by mechanical dropper (group M) at 1 ml·s− 1. Cough severity was graded as none (0), mild (1–2), moderate (3–5), or severe (> 5), and the incidence of SIC was evaluated for 5 min after the start of sufentanil injection. Other adverse reactions such as hypotension, hypertension, bradycardia, tachycardia, hypoxemia, vomiting, and aspiration during the induction period of general anesthesia were also observed. The primary outcome was the incidence of SIC. The secondary outcomes were the severity of SIC and other adverse reactions.ResultsThe incidence of SIC in group M was significantly lower than that in group C (2% versus 21%, P = 0.000), and the prevalence of moderately severe coughing was also statistically different (none in group M versus 11% in group C, P = 0.001). However, there were no statistical differences in the incidence of other adverse reactions between two groups (P > 0.05).ConclusionSufentanil application via mechanical dropper can significantly alleviate the occurrence of SIC during the induction phase of total intravenous general anesthesia. This method is simple, safe, and reliable, and has wide prospective application for clinical use.Trial registrationChinese Clinical Trial Register, ChiCTR-IOR-17011561. Registered on 3 June 2017.

Cilostazol Added to Dual Antiplatelet Therapy for Patients with High Risk of Restenosis after Drug-Eluting Stent Implantation: A Systematic Review and Meta-Analysis of RCTs

Background: Cilostazol added to Dual Antiplatelet Therapy (DAT: aspirin, clopidogrel) reduces revascularization without increased bleeding in patients after Drug-Eluting Stent (DES) implantation. However, doubts remain about which patients benefit most from cilostazol-based Triple Antiplatelet Therapy (TAT) after DES. Materials and Results: PubMed, EMBASE, CENTRAL databases were systematically searched. Randomized Controlled Trials (RCTs) comparing TAT and DAT for patients with high risk of restenosis (defined as obesity, diabetes, and long and/or multivessel coronary lesions) were included. Five RCTs were included, involving 2442 patients. The TAT group showed a significant reduction in MACEs (4.16% vs. 8.86%, RR: 0.47, 95% CI: 0.32 to 0.68, p<0.001), in-stent late loss (0.34 vs. 0.46, SMD: -0.22, 95% CI: -0.32 to -0.11, p<0.001), TVR (3.36% vs. 6.80%, RR: 0.49, 95% CI: 0.34 to 0.71, p<0.001), and in-stent restenosis (6.86% vs. 11.45%, RR: 0.60, 95% CI: 0.43 to 0.84, p=0.003) compared with the DAT group. There was no difference in all-cause mortality (1.56% vs. 0.82%, RR: 1.82, 95% CI: 0.87 to 3.77, p=0.110), bleeding (3.52% vs. 3.28%, RR: 1.07, 95% CI: 0.71 to 1.63, p=0.745) and stent thrombosis (0.82% vs. 0.66%, RR: 1.4, 95% CI: 0.50 to 3.06, p=0.641) between the two groups, whereas the incidence of other adverse reactions (11.38% vs. 6.39%, RR: 1.78, 95% CI: 1.37 to 2.33, p<0.001) and drug discontinuation (16.29% vs. 5.15%, RR: 4.60, 95% CI: 1.24 to 17.08, p=0.023) was greater in the TAT group than in the DAT group. Conclusions: Compared with DAT, patients with a high risk of restenosis benefited from TAT in reduced stent restenosis and revascularization after DES implantation, without increases in all-cause mortality and bleeding, but accompanied by a higher incidence of other adverse reactions and drug discontinuation.

Non‐thrombotic‐, non‐inhibitor‐associated adverse reactions to coagulation factor concentrates for treatment of patients with hemophilia and von Willebrand’s disease: a systematic review of prospective studies

In the last three decades there have been dramatic improvements in the availability and quality of treatment for people with inherited coagulation disorders. Indeed, the improvement of methods of purification and viral inactivation for plasma-derived coagulation factor concentrates first and then the development of products utilizing recombinant DNA technology have greatly improved the life expectancy of hemophiliacs, which has progressively become similar to that of males in the general population. Nowadays, the most frequent complication of factor replacement therapy for hemophilia is the development of inhibitors. However, no studies so far have systematically analysed the type and incidence of other adverse reactions following the administration of coagulation factor concentrates. The aim of this systematic review was to screen the published literature data to evaluate the types and frequencies of non-thrombotic-, non-inhibitor-associated adverse reactions to coagulation factor concentrates in patients with hemophilia A, hemophilia B and von Willebrand's disease. On behalf the European Haemophilia Safety Surveillance System (EUHASS), a systematic review of the prospective studies published in the last 20 years was performed using electronic databases and article references. Both severe and mild adverse events following infusion of coagulation factor concentrates are relatively rare in patients with inherited coagulation disorders; the most common events are of an allergic type. There are no differences in the rate of adverse events caused by plasma-derived or recombinant products. On the whole, these data confirm the high degree of safety of the products currently used for replacement therapy.

Ketoprofen, Diclofenac or Ketorolac for Pain After Tonsillectomy in Adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.

Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.