scholarly journals Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
James Patrick Finnerty ◽  
Aravind Ponnuswamy ◽  
Prosjenjit Dutta ◽  
Ammar Abdelaziz ◽  
Hafiz Kamil

Abstract Background Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF. Study design and methods A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies. Results 13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was − 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were − 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71. Interpretation Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Toshikazu Watanabe ◽  
Tomoyuki Minezawa ◽  
Midori Hasegawa ◽  
Yasuhiro Goto ◽  
Takuya Okamura ◽  
...  

Abstract Background Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. Results The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. Conclusions MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.


1998 ◽  
Vol 14 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Pramodini B Kale-Pradhan ◽  
Suzette R Habowski ◽  
Heather C Chase ◽  
Frank C Castronova

Objective: To compare the efficacy, nephrotoxicity, and ototoxicity of once-daily dosing of aminoglycosides versus conventional dosing. Design: Meta-analysis of 14 randomized trials identified through a MEDLINE search (January 1965-May 1996). Patients: Neutropenic and nonneutropenic adults. Interventions: Patients were randomly selected to receive an aminoglycoside once daily or in multiple daily doses. Measurements and Main Outcomes: The outcomes considered were clinical cure, bacteriologic cure, nephrotoxicity, auditory toxicity, and vestibular toxicity. The data were analyzed in the following subgroups: (1) all trials, (2) nonneutropenic patients, (3) neutropenic patients, and (4) patients with undefined neutrophil status. For all trials the pooled risk ratio was 1.268 (95% CI 0.828 to 1.939) for clinical cure, and was 1.390 (95% CI 1.350 to 1.392) for bacteriologic cure. Nephrotoxicity had a pooled risk ratio of 0.765 (95% CI 0.468 to 1.252), that for auditory toxicity was 1.117 (95% CI 0.151 to 5.636), and that for vestibular toxicity was 1.155 (95% CI 0.221 to 6.039). Analysis of the subgroups, including a separate analysis of neutropenic patients, demonstrated similar results. Conclusions: When all trials were considered, once-daily administration of aminoglycosides had similar efficacy and no increase in nephrotoxicity or ototoxicity compared with conventional aminoglycoside dosing.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S168-S168
Author(s):  
Dan Siskind ◽  
Brian Wu ◽  
Tommy Wong ◽  
Steve Kisely

Abstract Background People living with schizophrenia are 3 times more likely to smoke than the general population, and have fewer and less successful quitting attempts. In concert with psychosocial quit interventions, there is a need for evidence based pharmacological interventions to assist people living with schizophrenia achieve smoking abstinence. Methods We systematically searched PubMed, PsycInfo, EMBASE and Cochrane for randomised controlled trials of pharmacological interventions for reducing smoking among people living with schizophrenia. We conducted pairwise and network meta-analyses of effectiveness of interventions for achieving abstinence and reduction in smoking. We also examined psychiatric and physical adverse events of interventions. Results Nineteen studies were included in the systematic review. Data was available for buproprion, varenicline and nicotine replacement therapy (NRT). Buproprion (RR 3.4, 95%CI 1.6–7.3, p=0.002), varenicline (RR 3.8, 95%CI 2.0–7.2, p&lt;0.001) and NRT (RR 4.3, 95%CI 1.7–10.7, p=0.002) were all associated with increased rates of abstinence in pairwise meta-analyses. In a network meta-analysis varenicline was superior to buproprion (RR 2.0, 95%CI 1.0–3.9), however there was no statistically significant difference between varenicline and NRT or buproprion and NRT. Varenicline was associated with higher rates of nausea than placebo. Discussion Buproprion, varenicline and NRT were all superior to placebo for achieving abstinence. Varenicline appears to be superior to buproprion for achieving abstinence, however varenicline is associated with higher rates of nausea.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000706
Author(s):  
Ik Hur Teoh ◽  
Moulinath Banerjee

BackgroundRanolazine is an antianginal drug reported to have hypoglycaemic effects.ObjectivesTo assess the effect of ranolazine versus placebo on glycaemic control for adults with and without diabetes.MethodsA systematic search of seven databases was conducted to identify all randomised controlled trials that compared the effect of ranolazine versus placebo on haemoglobin A1c (HbA1c) and/or fasting plasma glucose (FPG) and/or incidence of hypoglycaemia. We used mean differences in HbA1c and FPG to express intervention effect estimates and analysed the data with random-effects model for meta-analyses using Revman 5.3.ResultsWe identified seven trials including 6543 subjects to assess the effect of ranolazine on HbA1c and/or FPG. A separate trial that included 944 subjects was included to assess the effect of ranolazine on hypoglycaemia. The change in HbA1c for all patients was −0.36% (95% CI −0.57% to −0.15%; p=0.0004, I2=78%). In patients with diabetes, the change in HbA1c was −0.41% (95% CI −0.58% to −0.25%; p<0.00001, I2=65%). There was no significant difference in FPG between ranolazine and placebo groups (−2.58 mmol/L, 95% CI −7.02 to 1.85; p=0.25; I2=49%) or incidence of hypoglycaemia between ranolazine and placebo groups (OR 1.70, 95% CI 0.89 to 3.26; p=0.61, I2=0%).ConclusionsOur meta-analytic findings support the fact that ranolazine improves HbA1c without increasing the risk of hypoglycaemia. It therefore has a potential of having an additional benefit of improving glycaemic control in patients with chronic stable angina and diabetes.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044356
Author(s):  
Benjamin Ng ◽  
Magnus Fugger ◽  
Igho Jovwoke Onakpoya ◽  
Andrew Macdonald ◽  
Carl Heneghan

IntroductionPatients with end-stage renal disease may require arteriovenous (AV) access in the form of arteriovenous fistulae (AVFs) or arteriovenous grafts (AVGs) for haemodialysis. AV access dysfunction requires intervention such as plain balloon angioplasty or covered stents to regain patency.AimTo systematically review and meta-analyse the patency outcomes of covered stents in failing haemodialysis AV access, compared with balloon angioplasty.MethodsThe review was first registered on the International Prospective Register of Systematic Reviews (CRD42018069955) before data collection. We searched six electronic databases to identify relevant randomised controlled trials (RCTs) up until August 2020, without language restriction. Two reviewers assessed the suitability and quality of studies for inclusion using the Consolidated Standards of Reporting Trials guidelines. We meta-analysed data using a random-effects model.ResultsWe included seven studies including 1147 patients in the systematic review, of which 867 had AVGs and 280 had AVFs. One study was an ongoing RCT. In the meta-analyses, we assessed patients with failing AVGs only. Overall risk of bias was moderate. Covered stents were associated with lower loss of patency versus angioplasty alone at 6, 12 and 24 months (OR 4.48, 95% CI 1.98 to 10.14, p<0.001; OR 4.07, 95% CI 1.74 to 9.54, p=0.001; OR 2.24, 95% CI 1.17 to 4.29, p=0.01, respectively). Covered stents afforded superior access circuit primary patency compared with angioplasty alone at 6 and 12 months (OR 1.91, 95% CI 1.31 to 2.80, p<0.001; OR 1.97, 95% CI 1.14 to 3.41, p=0.02, respectively). This was not significant at 24 months. There was no significant difference in loss of secondary patency between groups at 12 or 24 months (OR 0.74, 95% CI 0.45 to 1.23, p=0.25; OR 0.67, 95% CI 0.29 to 0.154, p=0.34, respectively).ConclusionOur results support use of covered stents over angioplasty alone, at 6, 12 and 24 months in failing AVGs. Further clinical trials are warranted.


1997 ◽  
Vol 170 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Matthew Hotopf ◽  
Rebecca Hardy ◽  
Glyn Lewis

BackgroundPrevious meta-analyses suggest that individuals treated with serotonin-specific reuptake inhibitors (SSRIs) in randomised controlled trials (RCTs) are less likely to discontinue treatment than those on tricyclic antidepressants. This metaanalysis investigates whether this is due to the frequent use in RCTs of older reference tricyclics (imipramine and amitriptyline), which may have worse side-effects than more recent compounds.MethodsA meta-analysis of RCTs comparing tricyclic and heterocyclic antidepressants with SSRIs in the treatment of depression.ResultsThe overall odds ratio of discontinuation on tricyclic/heterocyclic antidepressants compared with SSRIs was 0.86 (95% CI 0.78–0.94). The odds ratio for reference tricyclics was 0.82 95% CI 0.72–0.23), newer tricyclics 0.89 (95% CI 0.74–1.06), and heterocyclics 1.02 (95% CI 0.78–1.35). The pooled advantage of SSRIs over tricyclics was maintained whether the population studied consisted of younger adults or only the elderly. No differences in discontinuation rates were detected between the SSRIs.ConclusionsThe lower rate of discontinuation in patients on SSRIs may be due to the use of old tricyclics (which have worse side-effects) as reference compounds. The SSRIs do not show a statistically significant difference in discontinuation rates when compared with newer tricyclics or heterocyclics.


2022 ◽  
Vol 16 ◽  
pp. 263235242110705
Author(s):  
Carol Chunfeng Wang ◽  
Ellen Yichun Han ◽  
Mark Jenkins ◽  
Xuepei Hong ◽  
Shuqin Pang ◽  
...  

Introduction: This study aimed to synthesise the best available evidence on the safety and efficacy of using moxibustion and/or acupuncture to manage cancer-related insomnia (CRI). Methods: The PRISMA framework guided the review. Nine databases were searched from its inception to July 2020, published in English or Chinese. Randomised clinical trials (RCTs) of moxibustion and or acupuncture for the treatment of CRI were selected for inclusion. Methodological quality was assessed using the method suggested by the Cochrane collaboration. The Cochrane Review Manager was used to conduct a meta-analysis. Results: Fourteen RCTs met the eligibility criteria. Twelve RCTs used the Pittsburgh Sleep Quality Index (PSQI) score as continuous data and a meta-analysis showed positive effects of moxibustion and or acupuncture ( n = 997, mean difference (MD) = −1.84, 95% confidence interval (CI) = −2.75 to −0.94, p < 0.01). Five RCTs using continuous data and a meta-analysis in these studies also showed significant difference between two groups ( n = 358, risk ratio (RR) = 0.45, 95% CI = 0.26–0.80, I2 = 39%). Conclusion: The meta-analyses demonstrated that moxibustion and or acupuncture showed a positive effect in managing CRI. Such modalities could be considered an add-on option in the current CRI management regimen.


2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.


2019 ◽  
Vol 17 (2) ◽  
pp. 191-203
Author(s):  
Oliver Brown ◽  
Jennifer Rossington ◽  
Gill Louise Buchanan ◽  
Giuseppe Patti ◽  
Angela Hoye

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. </P><P> Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. </P><P> Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. </P><P> Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.


2021 ◽  
Vol 09 (07) ◽  
pp. E1128-E1135
Author(s):  
Xianhong Zhao ◽  
Yangxue Huang ◽  
Jiarong Li ◽  
Aoqiang Zhou ◽  
Gengxin Chen ◽  
...  

Abstract Background and study aims Delayed bleeding and thrombotic events are uncontrolled adverse events that are hard to balance in patients receiving anticoagulants after endoscopic resection. The present study aims to assess the clinical effect of warfarin, when compared to direct oral anticoagulants (DOACs), in terms of delayed bleeding and thrombotic events. Methods A comprehensive electronic literature search was conducted for eligible literature. Pairwise meta-analyses were performed on outcomes of delayed bleeding and thrombotic events. Two networks within the Bayesian framework were established based on the management of anticoagulants and type of DOAC. Results Eight cohort studies with 2,046 patients were eligible for inclusion, including 1,176 patients treated with warfarin and 870 with DOACs. There was no significant difference between warfarin and DOACs, in terms of delayed bleeding (OR = 1.29, 95 % CI [0.99–1.69]) and thromboembolism (OR = 2.0, 95 % CI [0.32–12.39]). In the network meta-analyses for delayed bleeding, the rank probabilities revealed that the safest management was discontinuous warfarin without heparin bridge therapy (HBT). Rank probabilities for the types of DOACs demonstrated that the safest drug was dabigatran. Conclusions There was no significant difference in delayed bleeding and thromboembolism between warfarin and DOACs in patients receiving endoscopic treatment. In terms of delayed bleeding, discontinuous warfarin without HBT was suggested as the best management, and dabigatran was recommended as the best type of DOAC.


Sign in / Sign up

Export Citation Format

Share Document