scholarly journals Imiquimod versus podophyllotoxin, with and without human papillomavirus vaccine, for anogenital warts: the HIPvac factorial RCT

2020 ◽  
Vol 24 (47) ◽  
pp. 1-86
Author(s):  
Richard Gilson ◽  
Diarmuid Nugent ◽  
Kate Bennett ◽  
Caroline J Doré ◽  
Macey L Murray ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Primary Outcome ◽  
Human Papillomavirus Vaccine ◽  
Anogenital Warts ◽  
Imiquimod Cream ◽  
History Of ◽  
Papillomavirus Vaccine

Background The comparative efficacy, and cost-effectiveness, of imiquimod or podophyllotoxin cream, either alone or in combination with the quadrivalent HPV vaccine (Gardasil®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) in the treatment and prevention of recurrence of anogenital warts is not known. Objective The objective was to compare the efficacy of imiquimod and podophyllotoxin creams to treat anogenital warts and to assess whether or not the addition of quadrivalent human papillomavirus vaccine increases wart clearance or prevention of recurrence. Design A randomised, controlled, multicentre, partially blinded factorial trial. Participants were randomised equally to four groups, combining either topical treatment with quadrivalent human papillomavirus vaccine or placebo. Randomisation was stratified by gender, a history of previous warts and human immunodeficiency virus status. There was an accompanying economic evaluation, conducted from the provider perspective over the trial duration. Setting The setting was 22 sexual health clinics in England and Wales. Participants Participants were patients with a first or repeat episode of anogenital warts who had not been treated in the previous 3 months and had not previously received quadrivalent human papillomavirus vaccine. Interventions Participants were randomised to 5% imiquimod cream (Aldara®; Meda Pharmaceuticals, Takeley, UK) for up to 16 weeks or 0.15% podophyllotoxin cream (Warticon®; GlaxoSmithKlein plc, Brentford, UK) for 4 weeks, which was extended to up to 16 weeks if warts persisted. Participants were simultaneously randomised to quadrivalent human papillomavirus vaccine (Gardasil) or saline control at 0, 8 and 24 weeks. Cryotherapy was permitted after week 4 at the discretion of the investigator. Main outcome measures The main outcome measures were a combined primary outcome of wart clearance at week 16 and remaining wart free at week 48. Efficacy analysis was by logistic regression with multiple imputation for missing follow-up values; economic evaluation considered the costs per quality-adjusted life-year. Results A total of 503 participants were enrolled and attended at least one follow-up visit. The mean age was 31 years, 66% of participants were male (24% of males were men who have sex with men), 50% had a previous history of warts and 2% were living with human immunodeficiency virus. For the primary outcome, the adjusted odds ratio for imiquimod cream versus podophyllotoxin cream was 0.81 (95% confidence interval 0.54 to 1.23), and for quadrivalent human papillomavirus vaccine versus placebo, the adjusted odds ratio was 1.46 (95% confidence interval 0.97 to 2.20). For the components of the primary outcome, the adjusted odds ratio for wart free at week 16 for imiquimod versus podophyllotoxin was 0.77 (95% confidence interval 0.52 to 1.14) and for quadrivalent human papillomavirus vaccine versus placebo was 1.30 (95% confidence interval 0.89 to 1.91). The adjusted odds ratio for remaining wart free at 48 weeks (in those who were wart free at week 16) for imiquimod versus podophyllotoxin was 0.98 (95% confidence interval 0.54 to 1.78) and for quadrivalent human papillomavirus vaccine versus placebo was 1.39 (95% confidence interval 0.73 to 2.63). Podophyllotoxin plus quadrivalent human papillomavirus vaccine had inconclusive cost-effectiveness compared with podophyllotoxin alone. Limitations Hepatitis A vaccine as control was replaced by a saline placebo in a non-identical syringe, administered by someone outside the research team, for logistical reasons. Sample size was reduced from 1000 to 500 because of slow recruitment and other delays. Conclusions A benefit of the vaccine was not demonstrated in this trial. The odds of clearance at week 16 and remaining clear at week 48 were 46% higher with vaccine, and consistent effects were seen for both wart clearance and recurrence separately, but these differences were not statistically significant. Imiquimod and podophyllotoxin creams had similar efficacy for wart clearance, but with a wide confidence interval. The trial results do not support earlier evidence of a lower recurrence with use of imiquimod than with use of podophyllotoxin. Podophyllotoxin without quadrivalent human papillomavirus vaccine is the most cost-effective strategy at the current vaccine list price. A further larger trial is needed to definitively investigate the effect of the vaccine; studies of the immune response in vaccine recipients are needed to investigate the mechanism of action. Trial registration Current Controlled Trials. Current Controlled Trials ISRCTN32729817 and EudraCT 2013-002951-14. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 47. See the NIHR Journals Library website for further project information.

scholarly journals Association Study between the Polymorphisms of Matrix Metalloproteinase (MMP) Genes and Idiopathic Recurrent Pregnancy Loss

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 347 ◽  
Author(s):  
Han Sung Park ◽  
Ki Han Ko ◽  
Jung Oh Kim ◽  
Hui Jeong An ◽  
Young Ran Kim ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Adjusted Odds Ratio ◽  
Recurrent Pregnancy Loss ◽  
Proteolytic Enzymes ◽  
Nucleotide Polymorphisms ◽  
Genotype Combination ◽  
History Of ◽  
Consecutive Pregnancy

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257–0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483–0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

Confidence intervals for the difference between two relative risks

2020 ◽  
Vol 29 (10) ◽  
pp. 3048-3058
Author(s):  
Joshua N Sampson ◽  
Mitchell H Gail
Keyword(s):  
Human Papillomavirus ◽  
Confidence Interval ◽  
Small Sample ◽  
Control Treatment ◽  
Human Papillomavirus Vaccine ◽  
Relative Risks ◽  
Vaccine Trials ◽  
The Difference ◽  
Small Sample Sizes ◽  
Papillomavirus Vaccine

We provide methods to estimate the confidence interval for the difference between two relative risks. Letting p0, p1, and p2 be the probabilities of an event in three groups (i.e. control, treatment 1, treatment 2), our methods estimate a confidence interval for r =  p1/ p0 −  p2/ p0. We highlight that our methods can handle small sample sizes, covariates, and study populations from multiple strata. We specifically developed these methods for vaccine trials to estimate the difference between two vaccine efficacies, where VE1 = 1 −  p1/ p0, VE2 = 1 −  p2/ p0 and r = VE2 − VE1. We showcase our methods by using interim data from one of these trials to suggest that one dose of the human papillomavirus vaccine may be as efficacious as two doses of the vaccine.

scholarly journals Predictors of hospital mortality among patients with COVID-19 in Tehran, Iran

2021 ◽  
Vol 9 ◽  
pp. 205031212110515
Author(s):  
Fatemeh Esfahanian ◽  
SeyedAhmad SeyedAlinaghi ◽  
Nazanin Janfaza ◽  
Marcarious M. Tantuoyir
Keyword(s):  
Logistic Regression ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Laboratory Data ◽  
Hospitalized Patients ◽  
Multivariate Logistic Regression ◽  
Predictors Of Mortality ◽  
Laboratory Test Results ◽  
History Of

Objective: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Timely and effective predictors of survival and death rates are crucial for improving the management of COVID-19 patients. In this study, we evaluated the predictors of mortality based on the demographics, comorbidities, clinical characteristics, laboratory findings, and vital signs of 500 patients with COVID-19 admitted at Imam Khomeini Hospital Complex, the biggest hospital in Tehran, Iran. Methods: Five hundred hospitalized laboratory-confirmed COVID-19 patients were included in this study. Subsequently, electronic medical records, including patient demographics, clinical manifestation, comorbidities, and laboratory test results were collected and analyzed. They were divided into two groups: expired and discharged. Demographics, clinical, and laboratory data were compared among the two groups. The related factors with death in the patients were determined using univariate and multivariate logistic regression approaches. Results: Among the 500 hospitalized patients, most patients were male (66.4% versus 33.6%). The expired group had more patients ⩾70 years of age compared with the discharged group (32.9% versus 16.3%, respectively). Almost 66% of the expired patients were hospitalized for ⩾5 days which was higher than the discharge group (26.9%). Patients with a history of opium use in the expired group were significantly higher compared to the discharged group (14.8% versus 8.6%, p = 0.04) as well as a history of cancer (15.5% versus 4.7%, p < 0.001). Out of the 500 patients with COVID-19, four patients (2.6%) were HIV positive, all of whom expired. Dyspnea (76.4%), fever (56.6%), myalgia (59.9%), and dry cough (67%) were the most common chief complaints of hospitalized patients. Age ⩾70 years (adjusted odds ratio = 2.49; 95% confidence interval, 1.02–6.04), being female (adjusted odds ratio = 2.06; 95% confidence interval, 1.25–3.41), days of hospitalization (adjusted odds ratio = 5.73; 95% confidence interval, 3.49–9.41), and having cancer (adjusted odds ratio = 3.23; 95% confidence interval, 1.42–7.39) were identified as independent predictors of mortality among COVID-19 patients. Conclusion: Discharged and expired COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principal component analysis. The mortality risk factors for severe patients identified in this study using a multivariate logistic regression model included elderly age (⩾70 years), being female, days of hospitalization, and having cancer.

scholarly journals Hypoxemia, Bradycardia, and Multiple Laryngoscopy Attempts during Anesthetic Induction in Infants

2019 ◽  
Vol 131 (4) ◽  
pp. 830-839 ◽  
Author(s):  
Jorge A. Gálvez ◽  
Samuel Acquah ◽  
Luis Ahumada ◽  
Lingyu Cai ◽  
Marcia Polanski ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Primary Outcome ◽  
Cross Sectional ◽  
Emergency Procedures ◽  
Academic Center ◽  
Healthy Infants ◽  
Increased Risk ◽  
History Of ◽  
American Society

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The infant airway is particularly vulnerable to trauma from repeated laryngoscopy attempts. Complications associated with elective tracheal intubations in anesthetized infants may be underappreciated. We conducted this study of anesthetized infants to determine the incidence of multiple laryngoscopy attempts during routine tracheal intubation and assess the association of laryngoscopy attempts with hypoxemia and bradycardia. Methods We conducted a retrospective cross-sectional cohort study of anesthetized infants (age less than or equal to 12 months) who underwent direct laryngoscopy for oral endotracheal intubation between January 24, 2015, and August 1, 2016. We excluded patients with a history of difficult intubation and emergency procedures. Our primary outcome was the incidence of hypoxemia or bradycardia during induction of anesthesia. We evaluated the relationship between laryngoscopy attempts and our primary outcome, adjusting for age, weight, American Society of Anesthesiologists status, staffing model, and encounter location. Results A total of 1,341 patients met our inclusion criteria, and 16% (n = 208) had multiple laryngoscopy attempts. The incidence of hypoxemia was 35% (n = 469) and bradycardia was 8.9% (n = 119). Hypoxemia and bradycardia occurred in 3.7% (n = 50) of patients. Multiple laryngoscopy attempts were associated with an increased risk of hypoxemia (adjusted odds ratio: 1.78, 95% CI: 1.30 to 2.43, P &lt; 0.001). There was no association between multiple laryngoscopy attempts and bradycardia (adjusted odds ratio: 1.23, 95% CI: 0.74 to 2.03, P = 0.255). Conclusions In a quaternary academic center, healthy infants undergoing routine tracheal intubations had a high incidence of multiple laryngoscopy attempts and associated hypoxemia episodes.

scholarly journals Determinants of short birth interval among ever married reproductive age women living in Jigjiga, Eastern Ethiopia 2020 (unmatched case–control study)

2021 ◽  
Vol 9 ◽  
pp. 205031212110678
Author(s):  
Abdurahman Kedir Roble ◽  
Mohamed Omar Osman ◽  
Ahmed Mohamed Ibrahim ◽  
Girma Tadesse Wedajo ◽  
Seid Abdi Usman
Keyword(s):  
Confidence Interval ◽  
Birth Interval ◽  
Odds Ratio ◽  
Neonatal Death ◽  
Adjusted Odds Ratio ◽  
Reproductive Age ◽  
Eastern Ethiopia ◽  
Short Birth Interval ◽  
History Of ◽  
Control Study

Objectives: A short birth interval is a universal public health problem resulting in adverse maternal, neonatal, and child outcomes. Therefore, the aim of this study was to identify determinants of short birth interval among ever married reproductive age mothers who live in Jigjiga city administration, Eastern Ethiopia, 2020. Methods: A community-based unmatched case–control study was used among 194 cases and 194 controls in Jigjiga city administration from September to December 2020. Cases were women with short birth interval (less than 3 years) and controls were women with optimum birth interval (3–5 years). Simple random sampling technique was employed to select cases and controls. Data were entered into Epi data version 4.2 and analysis with SPSS version 22. Binary logistic regression with 95% confidence interval at p < 0.05 is used to declare significantly associated predictors of short birth interval. Result: This study reported that women who have not attended formal education (adjusted odds ratio = 5.28, 95% confidence interval: (2.25–12.36)), attended primary education (adjusted odds ratio = 2.79, 95% confidence interval: (1.46–5.34)), women who married to a polygamous husband (adjusted odds ratio = 3.69, 95% confidence interval: (1.80–7.58)), having a history of neonatal death (adjusted odds ratio = 2.15, 95% confidence interval: (1.07–4.32)), preceding child being female (adjusted odds ratio = 3.69, 95% confidence interval: (2.02–6.72)), and never used contraceptive methods (adjusted odds ratio = 3.69, 95% confidence interval: (2.02–6.72)) were identified as determinants of the short birth interval. Conclusion: Short birth intervals were associated with educational level of the women, sex of the baby, husband marriage types, history of neonatal death, and contraceptive utilization. Strategy should be engaged to enhance women education, contraceptive uses, and to decrease neonatal death.

scholarly journals Determinants of neonatal sepsis among neonates delivered in Southwest Ethiopia 2018: A case-control study

2021 ◽  
Vol 9 ◽  
pp. 205031212110270
Author(s):  
Dejene Edosa Dirirsa ◽  
Bekem Dibaba Degefa ◽  
Alemayehu Dessale Gonfa
Keyword(s):  
Logistic Regression ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Confidence Interval ◽  
Neonatal Sepsis ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Southwest Ethiopia ◽  
Sexually Transmitted ◽  
History Of

Introduction: Neonatal sepsis is one of the principal causes of neonatal morbidity and mortality. In spite of interventions with different preventive methods, the burden of neonatal sepsis is being reported in different parts of Ethiopia. For further interventions, identifying its determinants is found to be essential. Objective: The study aimed to assess the determinants of neonatal sepsis among neonates delivered in Southwest Ethiopia in 2018. Methods: A hospital-based case-control study was conducted in Southwest Ethiopia from May 2018 to August 2018. Systematic random sampling technique was used to select study participants; Cases were neonates diagnosed with sepsis and controls were neonates without sepsis. Data were entered into Epi info version 7.2 and analyzed using Statistical Package for Social Sciences version 23. Bi-variable logistic regression was used to identify determinants of neonatal sepsis and those variables with a p-value < 0.05 in the multivariable logistic regression analysis were considered as significantly associated at a 95% confidence interval. Results: The findings from the multivariable logistic regression revealed that history of meconium-stained amniotic fluid (adjusted odds ratio [95% confidence interval] = 9.2 [1.1, 19.8]), history of foul-smelling liquor (adjusted odds ratio [95% confidence interval] = 5.2 [1.2, 22.3]), history of maternal sexually transmitted infection/urinary tract infection (adjusted odds ratio [95% confidence interval[ = 4.7 [1.1, 19.7]), history of vascular catheter (adjusted odds ratio [95% confidence interval] = 4.7 [1.11, 20]), and low birth weight (adjusted odds ratio [95% confidence interval] = 5.3 [1.3, 28.9]) were identified as determinants of neonatal sepsis. Conclusion: Generally, history of meconium-stained amniotic fluid, foul-smelling liquor, maternal history of the sexually transmitted disease, urinary tract infection, low birth weight, and the vascular catheter was identified as determinants of neonatal sepsis. Health education should be provided for pregnant mothers regarding health care-seeking behavior. Similarly, diagnoses and care should be accessible on time for foul-smelling liquor, premature rupture of membrane, and low birth weight.

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