Interventions to Increase Follow-Up of Abnormal Cervical Cancer Screening Results: A Systematic Literature Review and Meta-Analysis

INTRODUCTION: Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. OBJECTIVE: The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. METHODS: Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. FINDINGS: From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. CONCLUSION: Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions

Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial

Further to the patent expiry of Neupogen® (Amgen filgrastim), Hospira has developed a biosimilar filgrastim (Nivestim™) that may offer a clinically effective alternative for multiple hematologic and oncologic indications. Here results are reported from a phase I trial, primarily designed to compare the pharmacodynamic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, double-blind, randomized trial was undertaken to demonstrate equivalence of the pharmacodynamic characteristics of Hospira filgrastim and Amgen filgrastim. Fifty healthy volunteers were randomized to receive 5 or 10 µg/kg dosing, before further randomization to treatment sequence. All volunteers received five daily subcutaneous doses of Hospira filgrastim or Neupogen, with subsequent crossover to the alternative treatment. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of ‘test’ to ‘reference’ treatment means were within the conventional equivalence limits of 0.80–1.25, then bioequivalence was concluded. Forty-eight volunteers completed the study. Geometric mean absolute neutrophil count area under the curve from time 0 to the last time point at day 5 (primary endpoint) was comparable in volunteers given Hospira filgrastim or Amgen filgrastim at 5 µg/kg (ratio of means, 0.98; 90% CI, 0.92–1.05) or 10 µg/kg (ratio, 0.97; 90% CI, 0.93–1.01); 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim with regard to its pharmacodynamic characteristics

Addressing Cervical Cancer Disparities in Texas: Expansion of a Community-Based Prevention initiative For Medically Underserved Populations

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Pharmacokinetic-pharmacodynamic integration of danofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits

The pharmacokinetics of danofloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of 6 mg/kg to healthy rabbits. Danofloxacin concentration were determined by high-performance liquid chromatography assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of danofloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The danofloxacin plasma concentration versus time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and subcutaneously administered danofloxacin was best described by a one-compartment model. The terminal half-life for i.v., i.m. and s.c. routes was 4.88, 6.70 and 8.20 h, respectively. Clearance value after i.v. dosing was 0.76 L/kg.h. After i.m. administration, the absolute bioavailability was mean (+/- SD) 102.34 +/- 5.17% and the C-max was 1.87 mg/L. After s.c. administration, the absolute bioavailability was mean (+/- SD) 96.44 +/- 5.95% and the C-max was 1.79 mg/L. Danofloxacin shows a favourable pharmacokinetics profile in rabbits reflected by parameters such as a long half-life and a high bioavailability. However, in consideration of the low AUC/MIC indices obtained, its use by i.m. and s.c. route against the S. aureus strains assayed in this study cannot be recommended given the risk for selection of first mutant subpopulations

Pharmacokinetic-pharmacodynamic integration of moxifloxacin in rabbits after intravenous, intramuscular and oral administration

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Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis.

IntroductionEnsuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer.ObjectiveThe purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful.MethodsPublications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available.FindingsFrom 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed.ConclusionOur findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions