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2.
Influenza Other Respir Viruses ; 18(5): e13302, 2024 May.
Article En | MEDLINE | ID: mdl-38706384

BACKGROUND: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. METHODS: A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. RESULTS: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. CONCLUSION: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.


Antiviral Agents , Dibenzothiepins , Family Characteristics , Influenza, Human , Morpholines , Oseltamivir , Post-Exposure Prophylaxis , Pyridones , Triazines , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Influenza, Human/transmission , Pyridones/therapeutic use , Antiviral Agents/therapeutic use , Triazines/therapeutic use , Dibenzothiepins/therapeutic use , Female , Male , Oseltamivir/therapeutic use , Adult , Adolescent , Child , Middle Aged , Young Adult , Post-Exposure Prophylaxis/methods , Child, Preschool , Morpholines/therapeutic use , Thiepins/therapeutic use , Double-Blind Method , Infant , Pyridines/therapeutic use , Aged , Oxazines/therapeutic use
3.
Ann Palliat Med ; 13(2): 428-432, 2024 Mar.
Article En | MEDLINE | ID: mdl-38584476

BACKGROUND: Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant. CASE DESCRIPTION: The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems. CONCLUSIONS: The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.


Antiemetics , Antineoplastic Agents , Kidney Diseases , Prostatic Neoplasms , Respiratory Insufficiency , Male , Humans , Aged , Antiemetics/therapeutic use , Aprepitant/therapeutic use , Analgesics, Opioid/adverse effects , Oxycodone/adverse effects , Cytochrome P-450 CYP3A/therapeutic use , Morpholines/pharmacology , Morpholines/therapeutic use , Antineoplastic Agents/adverse effects , Drug Interactions , Prostatic Neoplasms/drug therapy , Pain/drug therapy , Respiratory Insufficiency/chemically induced , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy
4.
Br J Haematol ; 204(5): 1977-1985, 2024 May.
Article En | MEDLINE | ID: mdl-38566598

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.


Aminopyridines , Morpholines , Purpura, Thrombocytopenic, Idiopathic , Pyridines , Humans , Middle Aged , Female , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Male , Spain , Aminopyridines/therapeutic use , Aminopyridines/adverse effects , Aged , Morpholines/therapeutic use , Morpholines/adverse effects , Retrospective Studies , Adult , Pyridines/therapeutic use , Pyridines/adverse effects , Oxazines/therapeutic use , Oxazines/adverse effects , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Treatment Outcome , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Aged, 80 and over
5.
Cell Death Dis ; 15(4): 293, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664366

Research and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.


Autophagy , Cell Adhesion Molecules , Morpholines , Nectins , Urinary Bladder Neoplasms , Autophagy/drug effects , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/genetics , Humans , Animals , Cell Line, Tumor , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Mice , Morpholines/pharmacology , Morpholines/therapeutic use , Xenograft Model Antitumor Assays , Oligopeptides/pharmacology , Apoptosis/drug effects , Mice, Nude , Chromones/pharmacology , Chloroquine/pharmacology , Chloroquine/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Mice, Inbred BALB C , Female , Proto-Oncogene Proteins c-akt/metabolism
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 370-375, 2024 Apr.
Article Zh | MEDLINE | ID: mdl-38660838

OBJECTIVE: To analyze the efficacy and safety of flumatinib, a second-generation tyrosine kinase inhibitor (TKI) independently developed in China, in patients with chronic myelogenous leukemia in chronic phase (CML-CP) who falied first-line and second-line treatment. METHODS: The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively. Among them, 15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group, and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group. The hematological and molecular responses of the patients in the two groups at 3, 6 and 12 months of treatment, and the event-free survival (EFS) and adverse reactions of patients at the end of follow-up were statistical analyzed. RESULTS: At 3, 6, and 12 months of treatment, 10, 11, and 12 patients in the second line group achieved major molecular response (MMR), which was higher than that of 3, 4, and 5 patients in the third line group (P =0.010, P =0.011, P =0.010). At 3 months of treatment, 12 and 13 patients achieved complete hematological response (CHR) and early molecular response (EMR) in the second-line group, which was higher than that of 9 and 13 patients in the third-line group, but the difference between the two groups was not statistically significant (P =0.232, P =1.000); At 6 and 12 months of treatment, 6 and 7 patients in the second-line group achieved MR4.5, which were higher than of 3 and 2 cases in the third-line group, but the difference was not statistically significant (P =0.427, P =0.713). The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia, and no grade 3-4 of adverse reactions occurred. In the third-line group, there were 2 cases of grade 1-2 thrombocytopenia, grade 1-2 anemia and white blood cell 3 cases were reduced each, 1 case of grade 3-4 anemia, 2 cases of grade 3-4 neutropenia. The non-hematological adverse reactions in the second-line group were rash (2 cases), headache (1 case), diarrhea (1 case), fatigue (1 case), limb pain (1 case). There were 1 cases of diarrhea, 1 cases of nausea, and 1 cases of edema in the third-line group. There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients (P >0.05). At the end of follow-up, the EFS rate of patients in the second-line group was higher than that in the third-line group (100% vs 93.3%), but the difference was not statistically significant (P =0.317). CONCLUSION: The second-generation TKI flumatinib independently developed in China, has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.


Aminopyridines , Benzamides , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Retrospective Studies , Benzamides/therapeutic use , Female , Male , Aminopyridines/adverse effects , Imatinib Mesylate/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Middle Aged , Morpholines/therapeutic use , Dasatinib/therapeutic use , Dasatinib/adverse effects , Adult
8.
Int Immunopharmacol ; 130: 111811, 2024 Mar 30.
Article En | MEDLINE | ID: mdl-38457929

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.


Apoptosis , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Morpholines , Ocular Hypertension , Pyrroles , Retinal Ganglion Cells , TRPV Cation Channels , Tumor Necrosis Factor-alpha , Animals , Rats , Apoptosis/drug effects , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Disease Models, Animal , Glaucoma/drug therapy , Ocular Hypertension/drug therapy , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/pathology , TRPV Cation Channels/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , Morpholines/pharmacology , Morpholines/therapeutic use , Pyrroles/pharmacology , Pyrroles/therapeutic use
9.
Clin Invest Med ; 47(1): 13-22, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38546381

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. After corticosteroids with or without intravenous immune globulin (first-line treatment), second-line treatment options include rituximab, splenectomy, thrombopoietin receptor agonists (TPO-RAs), and fostamatinib. In Canada, the choice of second-line therapy is influenced by access to medications. The goals of this narrative review are to 1) summarize the evidence for the use of TPO-RAs and other second-line therapies in ITP and 2) highlight differences in public funding criteria for TPO-RAs across provinces and territories in Canada. METHODS: We conducted a literature review of second-line therapies for ITP. We solicited information on public funding programs for TPO-RAs in Canada from health care providers, pharmacists, and provincial ministries of health. RESULTS: Head-to-head trials involving TPO-RAs, rituximab, splenectomy, and fostamatinib are lacking. There is substantial evidence of effect for TPO-RAs in improving platelet count levels, health-related quality of life, bleeding, and fatigue from placebo-controlled trials and observational studies; however, access to TPO-RAs through provincial funding programs in Canada is variable. Splenectomy failure is a prerequisite for the funding of TPO-RAs in Ontario, Manitoba, and Saskatchewan, but not in Alberta or Quebec. Other provinces either do not have access to public funding or funding is provided on a case-by-case basis. DISCUSSION: TPO-RAs are effective second-line therapies for the treatment of ITP; however, access is variable across Canada, which results in health disparities and poor uptake of international treatment guidelines.


Aminopyridines , Morpholines , Purpura, Thrombocytopenic, Idiopathic , Pyrimidines , Receptors, Thrombopoietin , Humans , Aminopyridines/therapeutic use , Morpholines/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Pyrimidines/therapeutic use , Quality of Life , Receptors, Thrombopoietin/agonists , Rituximab/therapeutic use
10.
Sci Rep ; 14(1): 7030, 2024 03 25.
Article En | MEDLINE | ID: mdl-38528113

The enhanced recovery after surgery (ERAS) protocol, including prokinetic medications, is commonly used to prevent postoperative ileus. Prospective studies evaluating the effectiveness of mosapride citrate, a prokinetic 5-hydroxytryptamine 4 receptor agonist, in patients undergoing gastrectomy within the ERAS framework are lacking. This double-blind randomized trial included patients who were scheduled for laparoscopic or robotic gastrectomy for gastric cancer. Participants were randomly assigned to either a control (placebo) or experimental (mosapride citrate) group, with drugs administered on postoperative days 1-5. Bowel motility was evaluated based on bowel transit time measured using radiopaque markers, first-flatus time, and amount of food intake. No significant differences were observed in baseline characteristics between the two groups. On postoperative day 3, no significant difference was observed in the number of radiopaque markers visible in the colon between the groups. All factors associated with bowel recovery, including the time of first flatus, length of hospital stay, amount of food intake, and severity of abdominal discomfort, were similar between the two groups. Mosapride citrate does not benefit the recovery of intestinal motility after minimally invasive gastrectomy in patients with gastric cancer. Therefore, routine postoperative use of mosapride citrate is not recommended in such patients.


Benzamides , Gastrectomy , Morpholines , Stomach Neoplasms , Humans , Benzamides/therapeutic use , Flatulence , Gastrectomy/adverse effects , Gastrectomy/methods , Laparoscopy/methods , Length of Stay , Morpholines/therapeutic use , Postoperative Complications/prevention & control , Prospective Studies , Stomach Neoplasms/surgery , Treatment Outcome
11.
Cell Biol Toxicol ; 40(1): 12, 2024 02 10.
Article En | MEDLINE | ID: mdl-38340268

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.


Asthma , Dibenzothiepins , Pneumonia , Pyridones , Triazines , Animals , Mice , Asthma/drug therapy , Asthma/metabolism , Morpholines/pharmacology , Morpholines/therapeutic use
12.
Expert Rev Hematol ; 17(1-3): 55-66, 2024.
Article En | MEDLINE | ID: mdl-38369947

INTRODUCTION: Immune thrombocytopenia (ITP), a disease that commonly presents with an increased risk of bleeding, can also paradoxically produce an increased risk of thromboembolic events. The risk of thromboembolism can be associated with patient-related factors (e.g. co-morbidities, age and history of thrombosis), disease-related factors (e.g. a greater proportion of younger, more reactive platelets, and the presence of microparticles and pro-inflammatory cytokines) and treatment-related factors (e.g. splenectomy, thrombopoietin receptor agonists, and IVIg). AREAS COVERED: Aspects of the pathophysiology of ITP and the effects of treatment are discussed with emphasis on individualizing treatment based on the patient's thromboembolic risk, treatment options and preferences. EXPERT OPINION: An increased understanding of the pathophysiology of ITP has led to the development of new agents such as fostamatinib, a spleen tyrosine kinase inhibitor. Further research into the factors contributing to the risks for bleeding and thromboembolic events can contribute to the development of more specific therapies for ITP and allow greater individualization of therapy based on each patient's medical history and clinical status.


Purpura, Thrombocytopenic, Idiopathic , Pyrimidines , Thrombocytopenia , Thrombosis , Humans , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Aminopyridines/therapeutic use , Morpholines/therapeutic use , Thrombocytopenia/drug therapy , Pyridines/therapeutic use , Thrombosis/etiology , Thrombosis/drug therapy
16.
Clin Pharmacol Ther ; 115(1): 135-138, 2024 01.
Article En | MEDLINE | ID: mdl-37867292

All patients treated with anticancer agents should receive the most effective anti-emetic regimen. Anti-emetic guidelines provide recommendations but do not take into account possible drug-drug interactions between anti-emetics and anticancer drugs. This study determines the clinical relevance of the potential drug-drug interaction of the neurokinin-1 receptor antagonist, aprepitant, on the pharmacokinetics of etoposide. Aprepitant is a moderate CYP3A4 inhibitor and may increase the systemic exposure of etoposide which is partly metabolized by cytochrome P450 enzyme 3A4 (CYP3A4). In this prospective observational study, the pharmacokinetics of etoposide with and without concomitant use of aprepitant was determined in 12 patients receiving first-line chemotherapy for testicular cancer. The geometric mean (95% confidence interval (CI)) area under the plasma concentration-time curve 0-24 hour (AUC0-24h ) of etoposide with aprepitant was 86.2 (79.7-93.2) mg/L*hour vs. 83.7 (75.8-92.4) mg/L*hour without aprepitant. Geometric mean ratios (90% CIs) of AUC0-24h and maximum plasma concentration (Cmax ) for etoposide with and without aprepitant were 1.03 (0.96-1.10) and 0.96 (0.89-1.03), respectively. This study confirms the absence of a clinically relevant interaction between etoposide and aprepitant. Both drugs can be safely combined without affecting etoposide exposure.


Antiemetics , Antineoplastic Agents , Testicular Neoplasms , Male , Humans , Aprepitant , Etoposide , Testicular Neoplasms/chemically induced , Testicular Neoplasms/drug therapy , Morpholines/therapeutic use , Antineoplastic Agents/adverse effects
17.
J Pain Palliat Care Pharmacother ; 38(1): 28-32, 2024 Mar.
Article En | MEDLINE | ID: mdl-37983131

Intractable nausea can occur in numerous settings. We report on a 49-year-old woman with a past medical history of cystic fibrosis (CF) with chronic hypoxia, chronic nausea, complex infection history and frequent hospitalizations who was admitted to an academic medical center with a CF exacerbation. Her chronic nausea worsened with the use of antimicrobials, and she was unable to tolerate dopamine or serotonin antagonist antiemetics. Nausea persisted despite the use of benzodiazepines and antihistamines. She was given a one-time dose of fosaprepitant 150 mg intravenously (IV) with marked improvement of her nausea. During subsequent exacerbations, she again developed severe nausea which continued to respond well to a one-time dose of fosaprepitant 150 mg IV. Fosaprepitant is a substance P/neurokinin-1 (NK1) receptor antagonist that is FDA-approved for the prevention of chemotherapy-induced nausea and vomiting and has been used to prevent post-operative nausea and vomiting. Its use in other contexts has not been well established. This case suggests a role for fosaprepitant in the management of nausea outside the context of chemotherapy or general anesthesia.


Anti-Infective Agents , Morpholines , Female , Humans , Middle Aged , Morpholines/therapeutic use , Postoperative Nausea and Vomiting , Academic Medical Centers
19.
Medicine (Baltimore) ; 102(47): e35952, 2023 Nov 24.
Article En | MEDLINE | ID: mdl-38013306

BACKGROUND: Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV. METHODS: A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity. RESULTS: A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower. CONCLUSIONS: Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety.


Antiemetics , Antineoplastic Agents , Humans , Aprepitant/therapeutic use , Antiemetics/therapeutic use , Receptors, Serotonin, 5-HT3/therapeutic use , Morpholines/therapeutic use , Antineoplastic Agents/adverse effects , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/prevention & control , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Dexamethasone/therapeutic use
20.
Can J Anaesth ; 70(11): 1828-1838, 2023 11.
Article En | MEDLINE | ID: mdl-37917331

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.


RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.


Atrial Fibrillation , Cardiac Surgical Procedures , Humans , Atrial Fibrillation/etiology , Atrial Fibrillation/prevention & control , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Cardiac Surgical Procedures/adverse effects , Morpholines/therapeutic use , Randomized Controlled Trials as Topic
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