scholarly journals FRI0539 SURVIVAL IN PATIENTS WITH CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION (CTD-PAH): A META-ANALYSIS OF OBSERVATIONAL REGISTRIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 870.2-871
Author(s):  
D. Khanna ◽  
C. Zhao ◽  
L. Chung ◽  
G. Coghlan ◽  
R. Saggar ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Survival Data ◽  
Meta Analysis ◽  
Survival Rates ◽  
Small Sample ◽  
Class Iii ◽  
Inclusion Criteria ◽  
Research Support ◽  
Risk Of Death ◽  
The Impact

Background:Although patients with CTD-PAH comprise approximately one third of the overall PAH population, the literature on survival outcomes in CTD-PAH patients overall and by CTD subtype is limited by small sample sizes. We conducted a meta-analysis of more than 4,000 patients with CTD-PAH enrolled in observational registries.Objectives:To determine survival rates in patients with CTD-PAH overall and by CTD subtypes.Methods:The PubMed and EMBASE databases were searched for English-only articles published between January 1, 2000 and November 25, 2019. Inclusion criteria were multicenter registries of adults with WHO group 1 pulmonary hypertension (PAH); conducted in 2000 or later; and survival data for ≥30 patients with CTD-PAH. Meta-analysis of survival was performed using a random-effects model. Survival was estimated for CTD-PAH overall; for CTD-PAH stratified by registries primarily conducted before and after 2010 to assess the impact of new therapies, as well as combination therapy approaches targeting multiple pathways; and for CTD subtypes (systemic sclerosis [SSc] and systemic lupus erythematosus [SLE]).Results:Nineteen registries met inclusion criteria and reported data on 4,008 patients with CTD-PAH. Of these patients, 1,485 had SSc, 456 had SLE, and CTD subtype was not specified in 2,067. CTD-PAH patients had a mean age of 55 years and 87% were female. Most patients (70%) had functional class III or IV disease and the mean 6-minute walk distance at enrollment was 327 m. Among registries that enrolled patients of all PAH etiologies (N=7,829), survival rates in the CTD-PAH subpopulation (n=2113), were 83%, 73%, and 62% at 1-, 2-, and 3- years, respectively. These survival rates were lower than those reported for the overall PAH population: 88%, 79%, and 72% at 1-, 2-, and 3- years, respectively. Numerically higher survival rates at 1-, 2-, and 3- years were observed in CTD-PAH patients treated in 2010 and later: 85% vs 90%, 74% vs 82%, and 65% vs 73%. Among all CTD-PAH patients, survival rates were lower for patients with SSc compared to those with SLE: 88% vs 92%, 75% vs 90%, 67% vs 87% at 1-, 2-, and 3- years, respectively (Figure).Conclusion:Patients with CTD-PAH have a substantial risk of death, however, CTD-PAH patients treated within the last ten years have numerically higher survival rates than those treated earlier. This may be related to increased screening for PAH, especially in SSc (leading to earlier diagnosis) and/or the availability of new treatment approaches. Consistent with clinical observations, patients with SSc have worse survival rates than those with SLE. Given the high risk of mortality in these patients, early detection and upfront aggressive treatment are warranted.References:Acknowledgments:This analysis was funded by Actelion Pharmaceuticals.Disclosure of Interests:Dinesh Khanna Shareholder of: Eicos, Grant/research support from: NIH NIAID, NIH NIAMS, Consultant of: Acceleron, Actelion, Bayer, BMS, Boehringer-Ingelheim, Corbus, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-Aventis/Genzyme, UCB Pharma, Carol Zhao Shareholder of: Actelion Pharmaceuticals US, Inc., Employee of: Actelion Pharmaceuticals US, Inc., Lorinda Chung Grant/research support from: United Therapeutics, Boehringer Ingelheim, Consultant of: Bristol-Myers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos Sciences, Gerry Coghlan Grant/research support from: Johnson & Johnson, Consultant of: Bayer, Johnson & Johnson, GlaxoSmithKline, Speakers bureau: Bayer, Johnson & Johnson, GlaxoSmithKline, Rajan Saggar Grant/research support from: Actelion, Gilead Science, United Therapeutics, Consultant of: Actelion, Gilead Science, United Therapeutics, Speakers bureau: Actelion, Gilead Science, United Therapeutics, Stephen Mathai Consultant of: Actelion, Liquidia, Arena, United Therapeutics, Mehul Shah Shareholder of: Actelion Pharmaceuticals US, Inc, Employee of: Actelion Pharmaceuticals US, Inc, John Hartney Shareholder of: Actelion Pharmaceuticals US, Inc, Employee of: Actelion Pharmaceuticals US, Inc, Vallerie McLaughlin Grant/research support from: Reata Pharmaceutics, SoniVie, United Therapeutics, Bayer, Acceleron, Actelion Pharmaceuticals US, Inc., Consultant of: Actelion Pharmaceuticals US, Inc., Acceleron, Arena Pharmaceuticals, Bayer, Caremark, CiVi Biopharma, United Therapeutics

scholarly journals OP0131 ANIFROLUMAB EFFECTS ON RASH AND ARTHRITIS IN PATIENTS WITH SLE AND IMPACT OF INTERFERON SIGNAL IN POOLED DATA FROM PHASE 3 TRIALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 75-76
Author(s):  
J. T. Merrill ◽  
V. Werth ◽  
R. Furie ◽  
E. F. Morand ◽  
J. M. Kahlenberg ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Small Sample ◽  
Type I ◽  
Research Support ◽  
Phase 3 ◽  
Pooled Data ◽  
Link Type ◽  
The Impact

Background:Treatment with the type I interferon (IFN) receptor antibody anifrolumab was associated with clinical improvements in mucocutaneous and musculoskeletal disease activity in patients with systemic lupus erythematosus (SLE) in the phase 2 MUSE trial (NCT01438489) and phase 3 TULIP trials.1–4 Because rash and arthritis are the most common manifestations of SLE, the effect of anifrolumab on these symptoms can be examined in biomarker-defined subsets, as previously reported for the MUSE trial.2Objectives:To evaluate the effect of anifrolumab on rash and arthritis in patients with SLE, and the impact of IFN gene signature (IFNGS) on treatment response, using disease measures of different stringency in pooled data from the phase 3 TULIP trials.Methods:TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were placebo-controlled, 52-week trials of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE.3,4 In this post hoc analysis, outcomes of rash and arthritis were evaluated using mucocutaneous and musculoskeletal domains of the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) index. In addition, the modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) score was used to evaluate rash, and tender and swollen joint counts were used to assess arthritis.Results:360 patients received anifrolumab 300 mg (IFNGS test–high, n=298; IFNGS test–low, n=62) and 366 patients were given placebo (IFNGS test–high, n=302; IFNGS test–low, n=64). Change from baseline to Week 52 compared with placebo was measured by outcomes, ordered by their stringency. More anifrolumab-treated patients achieved rash improvement using SLEDAI-2K (complete resolution: difference 13.5%, nominal P<0.001), BILAG (at least 1 severity grade lowering: difference 15.5%, nominal P<0.001), and mCLASI (≥50% improvement, if baseline score >0: difference 15.6%, nominal P<0.001). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 17.0%, nominal P<0.001, BILAG: difference 16.1%, nominal P<0.001; mCLASI: difference 18.1%, nominal P<0.001). There was a trend toward anifrolumab-associated rash improvement in IFNGS test–low patients using BILAG (Figure). More patients receiving anifrolumab had SLEDAI-2K–defined resolution in arthritis (difference 8.2%, nominal P=0.029), BILAG severity lessening (difference 11.8%, nominal P=0.002), and ≥50% decrease in tender/swollen joint counts, when ≥6 at baseline (difference 12.6%, nominal P=0.016). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 11.7%, nominal P=0.005; BILAG: difference 12.9%, nominal P=0.003; joint counts: difference 11.3%, nominal P=0.054). In IFNGS test–low patients, there was a trend toward anifrolumab-associated arthritis improvement when measured using BILAG, and the effect of anifrolumab on the number of swollen/tender joint counts was similar to the IFNGS test–high group, although the IFNGS test–low sample size in this analysis was very small (Figure).Conclusion:In pooled data from the TULIP trials, anifrolumab treatment was associated with improvements in rash and arthritis using measures of different stringency. The SLEDAI-2K findings were largely driven by the subset of patients who were IFNGS test–high. However, using measures that were more sensitive to change, despite small sample sizes, IFNGS test–low patients may also have benefit.References:[1]Furie R, et al. Arthritis Rheumatol. 2017;69:376–86.[2]Merrill JT, et al. Lupus Sci Med. 2018;5:e000284.[3]Furie RA, et al. Lancet Rheumatol. 2019;1:e208–19.[4]Morand EF, et al. N Engl J Med. 2020;382:211–21.Acknowledgements:Writing assistance by Victoria Alikhan, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.Disclosure of Interests:Joan T Merrill Consultant of: AstraZeneca, AbbVie, Amgen, Aurinia, BMS, EMD Serono, GSK, Remegen, Janssen, Provention, and UCB, Grant/research support from: BMS and GSK, Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, J Michelle Kahlenberg Consultant of: Admirex Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, BMS, Boehringer Ingelheim, Eli Lilly, and Ventus Therapeutics, Grant/research support from: BMS/Celgene and Q32 Bio, Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

scholarly journals 749. Impact of Infectious Disease Consultation in Patients with Candidemia: A Retrospective study, Systematic Literature Review and Meta-analysis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S421-S422
Author(s):  
Takaaki Kobayashi ◽  
Alexandre Marra ◽  
Marin L Schweizer ◽  
Patrick Ten Eyck ◽  
Chaorong Wu ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Meta Analysis ◽  
Care Hospital ◽  
Inclusion Criteria ◽  
Research Support ◽  
Infectious Disease Consultation ◽  
The Impact ◽  
Overall Mortality

Abstract Background Morbidity and mortality from candidemia remain unacceptably high. While infectious disease consultation (IDC) is known to lower the mortality from Staphylococcus aureus bacteremia, little is known on the impact of IDC in candidemia. Methods We conducted a retrospective observational cohort study of candidemia patients at a large tertiary care hospital between 2015 and 2019. All patients aged ≥18 years with blood cultures positive for Candida species were included. We only included the first episode of candidemia. Exclusion criteria were death or transfer to the palliative care unit within 48 hours from the time cultures became positive. The crude mortality rate was compared between those with IDC and without IDC. Then, we systematically searched five publication-databases through February 2020 and performed a meta-analysis of the impact of IDC on mortality of patients with candidemia. The study protocol has been submitted to the International Prospective Register for Systematic Reviews (PROSPERO) database (ID 156939) on April 2020. Results A total of 151 patients at our institution met the inclusion criteria, 129 (85%) of whom received IDC. Thirty-day, and 90-day mortality rates were significantly lower in the IDC group (18% vs 50%, P = .002; 23% vs 50%, P = .0022, respectively). Our systematic literature review returned 216 reports, of which, 13 studies including ours fulfilled the inclusion criteria. Among the 13 studies with a total 3687 patients, IDC was performed in 49% of patients. Mortality numbers were available in 10 studies. Overall mortality was 38.2% with a significant difference in favor of the IDC group (28.4% and 47.6%) with a pooled relative risk of 0.41 [95% Cl 0.35-0.49]. Ophthalmology referral (61%; 790/1279 and 21%; 273/1304, P &lt; 0.001), echocardiogram (54%; 662/1219 and 28%; 369/1296, P &lt; 0.001), and central line removal (78%; 830/1069 and 61%; 686/1116, P &lt; 0.02) were performed more frequently among patients receiving IDC. Overall mortality Conclusion This study is the first systematic literature review and meta-analysis to evaluate the association between IDC and candidemia mortality. IDC was associated with a lower mortality and should be standard of care in all patients with candidemia. Disclosures Dimitrios Farmakiotis, MD, Astellas (Grant/Research Support) Paul Auwaerter, Collidion (Consultant)DiaSorin (Consultant)Johnson and Johnson (Shareholder)MicroB-Plex (Research Grant or Support)Shionogi (Consultant) Daniel Diekema, bioMerieux, Inc (Grant/Research Support)JMI Laboratories (Consultant)

scholarly journals Outcomes associated with modern treatment paradigms in connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH): a meta-analysis of randomized controlled trials (RCTs)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V McLaughlin ◽  
C Zhao ◽  
J.G Coghlan ◽  
L.S Chung ◽  
S.C Mathai ◽  
...  
Keyword(s):  
Drug Treatment ◽  
Treatment Effect ◽  
Meta Analysis ◽  
Response To Treatment ◽  
Funding Source ◽  
Class Iii ◽  
Inclusion Criteria ◽  
Private Company ◽  
Mortality Event

Abstract Background CTD-PAH has historically represented a PAH subtype with poor prognosis. New therapies, as well as combination therapy approaches targeting multiple pathways have been approved for PAH based on RCTs. CTD-PAH patients comprise a subgroup of the RCT populations and efficacy analyses are based on subgroup analyses which can be less reliable than the overall analysis. We conducted a meta-analysis of RCTs of approved PAH therapies to evaluate outcomes of patients with CTD-PAH. Purpose To use meta-analysis to determine response to treatment in patients with CTD-PAH. Methods The PubMed and EMBASE databases were searched for English-only articles published between January 1, 2000 and November 25, 2019. Inclusion criteria were multicenter RCTs that enrolled adults with WHO group 1 pulmonary hypertension (PAH); enrollment in 2000 or later; long-term clinical morbidity and/or mortality event or 6-minute walk distance (6MWD) as an efficacy endpoint reported for ≥30 patients with CTD-PAH; and evaluation of a US Food and Drug Administration-approved PAH therapy. The primary outcomes were treatment effect as measured by the study time to first morbidity or morality event and change in 6MWD from baseline to between 3–6 months, per the data provided in each article. Results from individual studies were combined using a random-effects model for overall study population (PAH patients) and the subgroup of CTD-PAH patients. Results Ten RCTs (N=4329 PAH patients; n=1263 (29%) with CTD-PAH) met inclusion criteria and were included in the meta-analysis. At baseline, PAH patients had a mean age of 50 years, approximately 78% were female, and approximately 58% had functional class III or IV disease. These characteristics were balanced between treatment and control groups. Baseline 6MWD was 356 m for the overall population and 337 m for patients with CTD-PAH. Five RCTs (N=3172; n=941 with CTD-PAH [30%]) reported hazard ratios (HRs) for time to a morbidity or mortality event by drug treatment and PAH etiology: overall population HR=0.63 (95% confidence interval [CI], 0.56–0.72; P&lt;0.001); CTD-PAH population HR=0.64 (95% CI, 0.51–0.80; P&lt;0.001) (Figure). Nine RCTs reported mean change with drug treatment from baseline to 3 to 6 months in 6MWD for PAH and CTD patients: 33.9 m (95% CI, 21.9–45.9; P&lt;0.001) in the overall population; 20.2 m (95% CI, 10.8–29.7; P&lt;0.001) in CTD-PAH patients. Conclusions The improvement in 6MWD in patients with CTD-PAH is smaller than in those with other types of PAH, perhaps reflecting comorbidities and CTD-induced mobility constraints, independent of their cardiopulmonary capacity. Data from long term clinical morbidity/mortality endpoint studies in this large group of patients with CTD-PAH demonstrate that these patients derive significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH. Treatment effect on morbidity/mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Actelion Pharmaceuticals US, Inc.

scholarly journals POS0698 BIIB059 DEMONSTRATED A CONSISTENT THERAPEUTIC EFFECT ON SRI-4 RESPONSE ACROSS SUBGROUPS OF PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE LILAC PHASE 2 STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 597-598
Author(s):  
R. Van Vollenhoven ◽  
R. Furie ◽  
K. Kalunian ◽  
S. Navarra ◽  
J. Romero-Diaz ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Response Rate ◽  
Small Sample ◽  
Statistical Testing ◽  
Type I ◽  
Phase 2 ◽  
Systemic Lupus ◽  
Research Support ◽  
Chemokine Production

Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K <10 versus ≥10, presence of BILAG-2004 grade A or B arthritis, oral corticosteroid usage, positivity for anti-ds DNA autoantibody and/or complement status, with point estimates for least-squares mean differences as well as corresponding 95% CIs consistently favoring BIIB059 (Figure 1). The incidence of adverse events in the overall study population was similar between the placebo and BIIB059 groups.2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.References:[1]Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. 2. Furie RA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0935.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Grant/research support from: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

scholarly journals Adjuvant HPV Vaccination to Prevent Recurrent Cervical Dysplasia after Surgical Treatment: A Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 410
Author(s):  
Violante Di Donato ◽  
Giuseppe Caruso ◽  
Marco Petrillo ◽  
Evangelos Kontopantelis ◽  
Innocenza Palaia ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Meta Analysis ◽  
Hpv Vaccination ◽  
Cervical Dysplasia ◽  
Reduction Rate ◽  
Intraepithelial Neoplasia ◽  
Surgical Excision ◽  
Inclusion Criteria ◽  
Mean Differences ◽  
The Impact

Objective: The aim of this meta-analysis was to discuss evidence supporting the efficacy of adjuvant human papillomavirus (HPV) vaccination in reducing the risk of recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical treatment. Methods: A systematic literature search was performed for studies reporting the impact of HPV vaccination on reducing the risk of recurrence of CIN 2+ after surgical excision. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Eleven studies met the inclusion criteria and were selected for analysis. In total, 21,310 patients were included: 4039 (19%) received peri-operational adjuvant HPV vaccination while 17,271 (81%) received surgery alone. The recurrence of CIN 2+ after treatment was significantly lower in the vaccinated compared with the unvaccinated group (OR 0.35; 95% CI 0.21–0.56; p < 0.0001). The recurrence of CIN 1+ after treatment was significantly lower in the vaccinated compared with the unvaccinated group (OR 0.51; 95% CI 0.31–0.83; p = 0.006). A non-significant trend of reduction rate of HPV persistence was observed in the vaccinated compared with the unvaccinated cohorts (OR was 0.84; 95% CI 0.61–1.15; p = 0.28). Conclusions: HPV vaccination, in adjuvant setting, is associated with a reduced risk of recurrent CIN 1+ and CIN 2+ after surgical treatment.

P–004 Effect of varicocelectomy on sperm DNA fragmentation rates in infertile men with clinical varicocele: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Tenori. Lir. Neto ◽  
M Roque ◽  
S Esteves
Keyword(s):  
Systematic Review ◽  
Surgical Technique ◽  
Dna Fragmentation ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Sperm Dna Fragmentation ◽  
Inclusion Criteria ◽  
Infertile Men ◽  
Sperm Dna ◽  
The Impact

Abstract Study question Does varicocelectomy improve sperm DNA quality in men with infertility and clinically detected varicoceles? Summary answer Varicocelectomy reduces sperm DNA fragmentation (SDF) rates in infertile men with clinical varicocele. What is known already Varicocele has been linked to male infertility through various non-mutually exclusive mechanisms, including an increase in reactive oxygen species (ROS) production that may lead to sperm DNA damage. Damage to sperm DNA may result in longer time-to-pregnancy, unexplained infertility, recurrent pregnancy loss, and failed intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection. Therefore, interventions aimed at decreasing SDF rates, including varicocele repair, have been explored to improve fertility and pregnancy outcomes potentially, either by natural conception or using medically assisted reproduction. Study design, size, duration Systematic review and meta-analysis Participants/materials, setting, methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our systematic search included PubMed/Medline, EMBASE, Scielo, and Google Scholar to identify all relevant studies written in English and published from inception until October 2020. Inclusion criteria were studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. Articles were included if the following SDF assays were utilized: SCSA, TUNEL, SCD test, or alkaline Comet. Main results and the role of chance Thirteen studies fulfilled the inclusion criteria and were selected for the analysis. The estimated weighted mean difference of SDF rates after varicocelectomy was –6.58% (13 studies, 95% CI –8.33%, –4.84%; I2=90% p &lt; 0.0001). Subgroup analysis revealed a significant decrease in SDF rates using SCSA (eight studies, WMD –6.80%, 95% CI –9.31%, –4.28%; I2=89%, p &lt; 0.0001), and TUNEL (three studies, WMD –4.86%, 95% CI –7.38%, –2.34%; I2=89%, p &lt; 0.0001). The test for subgroup difference revealed that pooled results were conservative using the above SDF assays. Comet and SCD tests were used in only one study each; thus, a meta-analysis was not applicable. The studies were further categorized by the surgical technique (microsurgical versus non-microsurgical). This subgroup analysis showed a significant decrease in SDF rates using microsurgical technique (10 studies, WMD –6.70%, 95% CI –9.04%, –4.37%; I2=91%, p &lt; 0.0001). After varicocelectomy, SDF rates were also decreased when non-microsurgical approaches were used, albeit the effect was not statistically significant (2 studies, WMD –6.84%, 95% CI –10.05%, 1.38%; I2=86%) (Figure 3). The heterogeneity was not materially affected by performing analyses by the above subgroups, suggesting that the SDF assay and surgical technique do not explain the inconsistency in the treatment effect across primary studies. Limitations, reasons for caution There were no randomized controlled trials comparing varicocelectomy to placebo for alleviating SDF levels. Heterogeneity was high, which may be explained by the low number of included studies. Pregnancy data are not available in most studies, thus the impact of reduced SDF after varicocelectomy on pregnancy rates unclear. Wider implications of the findings: Our study indicates a positive association between varicocelectomy and reduced postoperative SDF rates in men with clinical varicocele and infertility, independentetly of the assays used to measure SDF. These findings may help counsel and manage infertile men with varicocele and high SDF levels. Trial registration number Not applicable

Endoscopic pituitary surgery: a systematic review and meta-analysis

2009 ◽  
Vol 111 (3) ◽  
pp. 545-554 ◽  
Author(s):  
Abtin Tabaee ◽  
Vijay K. Anand ◽  
Yolanda Barrón ◽  
David H. Hiltzik ◽  
Seth M. Brown ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Pituitary Surgery ◽  
Small Sample ◽  
Csf Leak ◽  
Tumor Control ◽  
Published Data ◽  
Complication Rates ◽  
Short Term ◽  
The Impact

Object Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes. Methods The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes. Results Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67–89%). Hormone resolution was achieved in 81% (95% CI 71–91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76–92%) of growth hormone secreting tumors, and 82% (95% CI 70–94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0–4%) for CSF leak and 1% (95% CI 0–2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%. Conclusions The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

scholarly journals The effectiveness of psychological interventions for anxiety in the perinatal period: A systematic review and meta-analysis

2022 ◽  
Author(s):  
Natalie Clinkscales ◽  
Katherine Berlouis ◽  
Lisa Golds ◽  
Angus MacBeth
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Perinatal Period ◽  
Small Sample ◽  
Treatment Modalities ◽  
Cochrane Library ◽  
Psychological Interventions ◽  
Inclusion Criteria ◽  
Compulsive Disorder ◽  
Perinatal Anxiety

Background: Anxiety disorders are a relatively common occurring mental health issue during pregnancy and the perinatal period. There is evidence that untreated perinatal anxiety is a risk factor for adverse outcomes for mother and infant. Despite their potential acceptability to users, psychological interventions research for this population is still in its infancy. This systematic review and meta-analysis aimed to comprehensively evaluate the evidence of the effectiveness of psychological interventions for reducing perinatal anxiety. Method: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched included EMBASE, MEDLINE, PsychINFO, MIDIRS, CINAHL and the Cochrane Library. Search terms included: Psychological Therapy, Perinatal Period, Antenatal, Postnatal, Anxiety, Obsessive Compulsive Disorder and Phobia. Results: The search strategy identified 2025 studies. A total of 21 studies published between 2004 and 2021 fulfilled inclusion criteria. Of those, 17 were included in the meta-analysis. Overall results indicated that psychological interventions were more effective than control conditions in reducing symptoms of perinatal anxiety with a medium post treatment effect size. Significant effect sizes were also identified for online, face-to-face, group and guided self-help treatment modalities. Limitations: A small sample of studies are represented and limited to articles published in English. The review was unable to draw specific conclusions about what works (i.e. therapeutic modality/delivery) for whom (i.e. specific diagnoses) due to purposefully broad inclusion criteria. The longer-term effects of psychological interventions for perinatal anxiety and infant outcomes could not be established. Conclusions: This review demonstrates that psychological interventions are effective in reducing symptoms of both anxiety and comorbid anxiety and depression in the antenatal and postnatal periods. The results also demonstrate the efficacy of delivering such interventions in multiple settings, including online, and in group format. Further research is required to optimise treatment delivery to individual needs.

scholarly journals The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4462
Author(s):  
Konstantinos G. Kyriakoulis ◽  
Anastasios Kollias ◽  
Garyphallia Poulakou ◽  
Ioannis G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Severe Pneumonia ◽  
Hospitalized Patients ◽  
Current Evidence ◽  
Adjusted Risk ◽  
Risk Of Death ◽  
The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

Abstract 5133: Does Public Smoking Ban Reduce the Incidence of Myocardial Infarction in Michigan? A Systematic Review and Attributable Risk Analysis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mouaz Al-Mallah ◽  
Fadi Alqaisi ◽  
David Nerenz ◽  
Stephanie Boedeker ◽  
W. Douglas Weaver
Keyword(s):  
Hospital Admissions ◽  
Health Care Cost ◽  
Meta Analysis ◽  
Attributable Risk ◽  
Smoking Ban ◽  
Random Effects Model ◽  
Inclusion Criteria ◽  
Established Risk Factor ◽  
Potential Impact ◽  
The Impact

Background: Smoking is a well-established risk factor for cardiovascular disease. The Michigan legislature is currently considering a proposal for a comprehensive smoking ban (CSB) in Michigan. The potential impact of such a law on the incidence AMI is not known. We conducted a meta-analysis to study the impact of CSB on the incidence of AMI and calculated the impact of potential CSB on the incidence of AMI in Michigan. Methods: We searched MEDLINE, EMBASE, and Cochrane databases from inception till May 2008 for studies comparing the rates of AMI hospital admissions before and in the year after the implementation of CSB legislation. Of 135 potentially relevant articles screened initially, 5 studies met the inclusion criteria. A random-effects model meta-analysis was done and between-studies heterogeneity was compared with I2. The attributable risk (AR) of CSB on AMI incidence was calculated and multiplied with the number of AMI admissions in Michigan. Results: In the published studies, a CSB was associated with a decrease in the incidence of AMI (RR 96%, 95% CI 93%–100%, p=0.05). There was no heterogeneity between the included studies (I2<50%). The AR of CSB on the incidence of AMI is −4.2%. The average number of hospital admissions for AMI as first-listed diagnosis in Michigan between 1999 and 2006 was 27,007 per year. Thus, if a CSB legislation is implemented in Michigan in 2008, the calculated reduction of hospital admissions for AMI is 1130 admissions per year as of 2009.. Conclusion: CSB is associated with a significant reduction of annual hospital admissions for AMI. The financial impact of this reduction on health care cost is yet to be determined.

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