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Systematic review of analgesics and dexamethasone for post-tonsillectomy pain in adults.
Tolska, HK, Hamunen, K, Takala, A, Kontinen, VK
British journal of anaesthesia. 2019;(2):e397-e411
Abstract
BACKGROUND Intense pain can last several days after tonsillectomy. It is often undertreated and improved analgesic strategies that can be safely used at home are needed. METHODS We conducted a systematic review and meta-analysis on the effectiveness of systemic medications used for post-tonsillectomy pain in adult and adolescent (13 yr old) patients. Studies were identified from PubMed, the Cochrane Library, and by hand searching reference lists from studies and review articles. Randomised, double-blind, placebo-controlled studies reporting on pain intensity or use of rescue analgesia were included. RESULTS Twenty-nine randomised controlled trials representing 1816 subjects met the inclusion criteria. Follow-up time was ≤24 h in 15 studies, in which the majority were taking nonsteroidal anti-inflammatory drugs. Thirteen studies were suitable for meta-analysis. In pooled analysis, paracetamol, dexamethasone, and gabapentinoids reduced pain intensity on the day of operation. In individual studies, ketoprofen, ibuprofen, lornoxicam, parecoxib, rofecoxib, indomethacin and dextromethorphan reduced pain intensity, need for rescue analgesics, or both on the day of operation. Oral celecoxib for 2 postoperative weeks or i.v. ketamine on the day of operation were not effective at the studied doses. Dexamethasone in multiple doses provided analgesia beyond 1 postoperative day. Pain was moderate to strong in both study and control groups during the first postoperative week. CONCLUSIONS Single analgesics and dexamethasone provide only a weak to moderate effect for post-tonsillectomy pain on the day of operation and thus a multimodal analgesic strategy is recommended. Short follow-up times and clinical heterogeneity of studies limit the usefulness of results.
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Anti-vascular endothelial growth factor combined with intravitreal steroids for diabetic macular oedema.
Mehta, H, Hennings, C, Gillies, MC, Nguyen, V, Campain, A, Fraser-Bell, S
The Cochrane database of systematic reviews. 2018;(4):CD011599
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Abstract
BACKGROUND The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects. OBJECTIVES To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DMO. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 21 February 2018. SELECTION CRITERIA We included randomised controlled trials (RCTs) of intravitreal anti-VEGF combined with intravitreal steroids versus intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for managing DMO. We included people with DMO of all ages and both sexes. We also included trials where both eyes from one participant received different treatments. DATA COLLECTION AND ANALYSIS We used standard methodological procedures recommended by Cochrane.Two authors independently reviewed all the titles and abstracts identified from the electronic and manual searches against the inclusion criteria. Our primary outcome was change in best corrected visual acuity (BCVA) between baseline and one year. Secondary outcomes included change in central macular thickness (CMT), economic data and quality of life. We considered adverse effects including intraocular inflammation, raised intraocular pressure (IOP) and development of cataract. MAIN RESULTS There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). Seven studies used the unlicensed anti-VEGF agent bevacizumab and one study used licensed ranibizumab. The study that used licensed ranibizumab had a unique design compared with the other studies in that included eyes had persisting DMO after anti-VEGF monotherapy and received three monthly doses of ranibizumab prior to allocation. The anti-VEGF agent was combined with intravitreal triamcinolone in six studies and with an intravitreal dexamethasone implant in two studies. The comparator group was anti-VEGF alone in all studies; two studies had an additional steroid monotherapy arm, another study had an additional macular laser photocoagulation arm. Whilst we judged these studies to be at low risk of bias for most domains, at least one domain was at unclear risk in all studies.When comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA (mean difference (MD) -2.29 visual acuity (VA) letters, 95% confidence interval (CI) -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty evidence) or change in CMT (MD 0.20 μm, 95% CI -37.14 to 37.53; 3 RCTs; 188 eyes; low-certainty evidence) at one year. There was very low-certainty evidence on intraocular inflammation from 8 studies, with one event in the anti-VEGF/steroid group (313 eyes) and two events in the anti-VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-certainty evidence from one study of an increased risk of systemic adverse events in the anti-VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).One study compared anti-VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA (MD 4.00 VA letters 95% CI -2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 μm, 95% CI -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).One study provided very low-certainty evidence comparing anti-VEGF/steroid versus steroid monotherapy at one year. There was no evidence of a meaningful difference in BCVA between treatments at one year (MD 0 VA letters, 95% CI -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful difference in the mean CMT at one year (MD - 9 μm, 95% CI -39.87μm to 21.87μm between the anti-VEGF/steroid group and the steroid group. There was very low-certainty evidence on raised IOP at one year comparing the anti-VEGF/steroid versus steroid groups (Peto OR 0.75, 95% CI 0.16 to 3.55).No included study reported impact of treatment on patients' quality of life or economic data. None of the studies reported any cases of endophthalmitis. AUTHORS' CONCLUSIONS Combination of intravitreal anti-VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low-certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit. The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO. There is limited evidence from studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal steroid implants with at least one year follow-up. It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline.
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Letter to the Editor: Efficacy of the Intravitreal Sustained-Release Dexamethasone Implant for DME Refractory to Anti-VEGF Therapy: Meta-Analysis and Clinical Implications.
Hennings, C, Evans, J, Mehta, H
Ophthalmic surgery, lasers & imaging retina. 2018;(9):654-655
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Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions.
Chen, FC, Wang, LH, Zheng, XY, Zhang, XM, Zhang, J, Li, LJ
Oncotarget. 2017;(12):19236-19243
Abstract
BACKGROUND Dexamethasone premedication is required to prevent paclitaxel-related hypersensitivity reactions (HSRs). Oral dexamethasone (PO-D) has been considered the standard premedication regimen. However, whether intravenous dexamethasone (IV-D) is feasible for preventing paclitaxel-related HSRs is still unclear. We conducted a meta-analysis to compare these two regimens. METHODS We performed a systematic search in the PubMed, China National Knowledge Infrastructure, and Web of Science databases for relevant articles published before June 2016. Outcomes included HSRs and severe HSRs. Statistical analyses were performed using RevMan 5.2 software. RESULT Six studies comprising 1347 patients were included in the meta-analysis. The PO-D premedication regimen showed a significantly decreased incidence of severe HSRs compared with the IV-D regimen with an OR of 0.53 (95% CI 0.28-0.99, p = 0.05). However, there was no difference in the overall paclitaxel-related HSR rates between the two premedication regimens (OR 0.76, 95% CI 0.55-1.06, p = 0.11). Subgroup analyses according to study type and country of origin showed similar statistical results between the two premedication regimens. CONCLUSION Our meta-analysis showed that the PO-D premedication regimen is superior to the IV-D regimen in preventing paclitaxel-related HSRs. Additional randomized controlled trials are needed to confirm our findings.
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Efficacy of the Intravitreal Sustained-Release Dexamethasone Implant for Diabetic Macular Edema Refractory to Anti-Vascular Endothelial Growth Factor Therapy: Meta-Analysis and Clinical Implications.
Khan, Z, Kuriakose, RK, Khan, M, Chin, EK, Almeida, DR
Ophthalmic surgery, lasers & imaging retina. 2017;(2):160-166
Abstract
BACKGROUND AND OBJECTIVE To assess the effect on best-corrected visual acuity (BCVA) and efficacy of the intravitreal sustained-release 0.7 mg dexamethasone implant (Ozurdex; Allergan, Irvine, CA) in patients with recalcitrant diabetic macular edema (DME). PATIENTS AND METHODS Meta-analysis utilizing the MOOSE framework and a random effects model. Studies included adults undergoing treatment with Ozurdex for DME. The methodologic quality of each study was assessed using the MINORS and the Cochrane Collaboration Risk of Bias for randomized studies. RESULTS A total of 3,859 patients among 15 studies were included in the final analysis. The mean difference in BCVA was a gain of four lines or 20 Early Treatment of Diabetic Retinopathy Study letters with Ozurdex at a mean follow-up period of 6 months. CONCLUSIONS Treatment with Ozurdex is associated with significant mean improvement in visual acuity. Clinicians should have a multimodality approach to treating DME and be aware of this treatment option in those who have a suboptimal response to anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:160-166.].
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Late (> 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.
Doyle, LW, Cheong, JL, Ehrenkranz, RA, Halliday, HL
The Cochrane database of systematic reviews. 2017;(10):CD001145
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Abstract
BACKGROUND Many preterm infants who survive go on to develop bronchopulmonary dysplasia, probably as the result of persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established bronchopulmonary dysplasia. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES To examine the relative benefits and adverse effects of late systemic postnatal corticosteroid treatment (> 7 days) for preterm infants with evolving or established bronchopulmonary dysplasia. SEARCH METHODS For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA We selected for inclusion in this review randomised controlled trials (RCTs) comparing systemic postnatal corticosteroid treatment versus placebo or nothing initiated more than seven days after birth for preterm infants with evolving or established bronchopulmonary dysplasia. DATA COLLECTION AND ANALYSIS We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes including mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. MAIN RESULTS Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were RCTs, but methods used for random allocation were not always clear. Allocation concealment, blinding of the intervention, and blinding of outcome assessments most often were satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days) but no reduction in mortality at 36 weeks, at discharge, or at latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by 3, 7, or 28 days; bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age; need for late rescue treatment with dexamethasone; discharge on home oxygen; and death or bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age. Data revealed a trend towards increased risk of infection and gastrointestinal bleeding but no increase in risk of necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria, and hypertension. Investigators reported an increase in severe retinopathy of prematurity but no significant increase in blindness. Trial results showed a trend towards reduction in severe intraventricular haemorrhage, but only five studies enrolling 247 infants reported this outcome. Trends towards an increase in cerebral palsy or abnormal neurological examination findings were partly offset by a trend in the opposite direction involving death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability and the combined rate of death or major neurosensory disability were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure, or growth, although there were fewer participants with a clinically important reduction in forced expired volume in one second (FEV1) on respiratory function testing in the dexamethasone group.GRADE findings were high for all major outcomes considered, but review authors degraded the quality of evidence by one level because we found evidence of publication bias (bronchopulmonary dysplasia at 36 weeks). AUTHORS' CONCLUSIONS Benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. This review of postnatal systemic corticosteroid treatment for bronchopulmonary dysplasia initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of studies determining long-term outcomes is limited in some cases (some studies assessed surviving children only before school age, when some important neurological outcomes cannot be determined with certainty), and no studies were sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Evidence showing both benefits and harms of treatment and limitations of available evidence suggests that it may be prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation, and to minimise both dose and duration for any course of treatment.
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Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants.
Doyle, LW, Ehrenkranz, RA, Halliday, HL
The Cochrane database of systematic reviews. 2014;(5):CD001145
Abstract
BACKGROUND Many preterm infants who survive go on to develop chronic lung disease. This is probably due to persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established chronic lung disease. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES To determine the relative benefits and adverse effects associated with late (> 7 days) postnatal systemic corticosteroid treatment compared with control (placebo or nothing) in the preterm infant with evolving or established chronic lung disease. SEARCH METHODS We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 8), MEDLINE (1966 through August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. When possible, we contacted authors of all studies to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported. SELECTION CRITERIA We selected RCTs of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with evolving or established chronic lung disease for this review. DATA COLLECTION AND ANALYSIS We extracted and analysed data regarding clinical outcomes including mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications in the primary hospitalisation, and long-term health outcomes MAIN RESULTS Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were randomised controlled trials, but the methods for random allocation were not always clear. Allocation concealment, blinding of the intervention and blinding of the outcome assessments were mostly satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days), but not mortality at discharge or latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by three, seven or 28 days, chronic lung disease at both 28 days and 36 weeks' postmenstrual age, need for late rescue treatment with dexamethasone, discharge on home oxygen, and death or chronic lung disease at both 28 days and 36 weeks' postmenstrual age. There was a trend towards an increase in risk of infection and gastrointestinal bleeding, but not necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no significant increase in blindness. There was a trend towards a reduction in severe intraventricular haemorrhage, but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure or growth, although there were fewer with a clinically important reduction in the forced expired volume in one second (FEV1) on respiratory function testing. AUTHORS' CONCLUSIONS The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids, this review of postnatal corticosteroid treatment for chronic lung disease initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age, when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.