METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.
RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).
CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.
PATIENTS AND METHODS: In total, 100 eyes from 50 patients on long-term intranasal steroids (>2 y) for allergic rhinitis and 90 eyes from 45 controls were included in this study. Patients on other forms of steroids and risk factors for glaucoma were excluded. IOP was measured and nonmydriatic stereoscopic optic disc photos were taken for each eye. The vertical cup-to-disc ratio and the status of the optic disc were evaluated.
RESULTS: The mean IOP for intranasal steroids group was significantly higher (15.24±2.31 mm Hg) compared to the control group (13.91±1.86 mm Hg; P=0.000). However, there were no significant differences in the vertical cup-to-disc ratio and the status of glaucomatous optic disc changes between the groups.
CONCLUSIONS: Prolonged use of intranasal steroids cause statistical significant increase in IOP in patients with allergic rhinitis although no significant glaucomatous disc changes were seen. We suggest patients on long-term use of intranasal steroid have a yearly eye examination to be monitored for IOP elevation and those with additional risk factors for glaucoma is closely monitored for glaucoma.
OBJECTIVES: To assess the effects of peri-operative tranexamic acid versus no therapy or placebo on operative parameters in patients with chronic rhinosinusitis (with or without nasal polyps) who are undergoing functional endoscopic sinus surgery (FESS).
SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 February 2022.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing intravenous, oral or topical tranexamic acid with no therapy or placebo in the treatment of patients (adults and children) with chronic rhinosinusitis, with or without nasal polyps, undergoing FESS.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Primary outcome measures were surgical field bleeding score (e.g. Wormald or Boezaart grading system), intraoperative blood loss and significant adverse effects (seizures or thromboembolism within 12 weeks of surgery). Secondary outcomes were duration of surgery, incomplete surgery, surgical complications and postoperative bleeding (placing of packing or revision surgery) in the first two weeks after surgery. We performed subgroup analyses for methods of administration, different dosages, different forms of anaesthesia, use of thromboembolic prophylaxis and children versus adults. We evaluated each included study for risk of bias and used GRADE to assess the certainty of the evidence.
MAIN RESULTS: We included 14 studies in the review, with a total of 942 participants. Sample sizes in the included studies ranged from 10 to 170. All but two studies included adult patients (≥ 18 years). Two studies included children. Most studies had more male patients (range 46.6% to 80%). All studies were placebo-controlled and four studies had three treatment arms. Three studies investigated topical tranexamic acid; the other studies reported the use of intravenous tranexamic acid. For our primary outcome, surgical field bleeding score measured with the Boezaart or Wormald grading score, we pooled data from 13 studies. The pooled result demonstrated that tranexamic acid probably reduces the surgical field bleeding score, with a standardised mean difference (SMD) of -0.87 (95% confidence interval (CI) -1.23 to -0.51; 13 studies, 772 participants; moderate-certainty evidence). A SMD below -0.70 represents a large effect (in either direction). Tranexamic acid may result in a slight reduction in blood loss during surgery compared to placebo with a mean difference (MD) of -70.32 mL (95% CI -92.28 to -48.35 mL; 12 studies, 802 participants; low-certainty evidence). Tranexamic acid probably has little to no effect on the development of significant adverse events (seizures or thromboembolism) within 24 hours of surgery, with no events in either group and a risk difference (RD) of 0.00 (95% CI -0.02 to 0.02; 8 studies, 664 participants; moderate-certainty evidence). However, there were no studies reporting significant adverse event data with a longer duration of follow-up. Tranexamic acid probably results in little difference in the duration of surgery with a MD of -13.04 minutes (95% CI -19.27 to -6.81; 10 studies, 666 participants; moderate-certainty evidence). Tranexamic acid probably results in little to no difference in the incidence of incomplete surgery, with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence) and likely results in little to no difference in surgical complications, again with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence), although these numbers are too small to draw robust conclusions. Tranexamic acid may result in little to no difference in the likelihood of postoperative bleeding (placement of packing or revision surgery within three days of surgery) (RD -0.01, 95% CI -0.04 to 0.02; 6 studies, 404 participants; low-certainty evidence). There were no studies with longer follow-up.
AUTHORS' CONCLUSIONS: There is moderate-certainty evidence to support the beneficial value of topical or intravenous tranexamic acid during endoscopic sinus surgery with respect to surgical field bleeding score. Low- to moderate-certainty evidence suggests a slight decrease in total blood loss during surgery and duration of surgery. Whilst there is moderate-certainty evidence that tranexamic acid does not lead to more immediate significant adverse events compared to placebo, there is no evidence regarding the risk of serious adverse events more than 24 hours after surgery. There is low-certainty evidence that tranexamic acid may not change postoperative bleeding. There is not enough evidence available to draw robust conclusions about incomplete surgery or surgical complications.