Emerging Infectious Diseases Are Virulent Viruses-Are We Prepared? An Overview.

The recent pandemic caused by SARS-CoV-2 affected the global population, resulting in a significant loss of lives and global economic deterioration. COVID-19 highlighted the importance of public awareness and science-based decision making, and exposed global vulnerabilities in preparedness and response systems. Emerging and re-emerging viral outbreaks are becoming more frequent due to increased international travel and global warming. These viral outbreaks impose serious public health threats and have transformed national strategies for pandemic preparedness with global economic consequences. At the molecular level, viral mutations and variations are constantly thwarting vaccine efficacy, as well as diagnostic, therapeutic, and prevention strategies. Here, we discuss viral infectious diseases that were epidemic and pandemic, currently available treatments, and surveillance measures, along with their limitations.

Patient and provider prediabetes knowledge, attitudes, and behavior in a large urban family medicine practice.

Context: One-third of American adults have prediabetes. However, only 11% are aware of their condition, and they often do not receive prediabetes education or management. Prior studies have indicated knowledge gaps among primary care providers and patients on prediabetes management. Objective: To understand family medicine providers' and patients' attitudes, knowledge, and behaviors regarding prediabetes and its management to inform a prediabetes management intervention. Study Design: Cross-sectional surveys. Setting: A large academic family medicine practice in downtown Philadelphia with 30,000 patients making 80,000 visits annually. Population studied: Family medicine providers (attending physicians, nurse practitioners, residents) and adult patients seen within the last year, with HbA1c in the last 6 months between 5.7-6.4% (excluding pregnant, diabetes diagnosis). Instruments: Provider survey asking demographics, knowledge, attitudes, management, DPP awareness, barriers to prediabetes treatment, and open-ended question on how the practice could improve prediabetes management. Patient survey asking demographics, awareness of diagnosis and risk, knowledge, attitudes, experiences with DPP, prediabetes experiences with PCP, and same open-ended question as provider survey. Provider survey distributed via email; patient survey via Epic MyChart patient portal. Outcome Measures: Descriptive statistics for all quantitative survey items; thematic analysis of open-ended responses. Results: Fifty-four providers and 148 patients completed the surveys (57% and 16.5% response rates, respectively). Nearly all providers (96%) felt that prediabetes screening and management is important but most (74%) prescribe metformin to ≤ 25% of eligible patients. Over half (56%) were unaware of DPP, and 52% of those aware of DPP did not know how to refer a patient. Over half (59%) of patients reported having been told they have prediabetes and 84% thought diet and lifestyle changes were effective treatment, but 65% were unaware of medication options and only 5% had been referred to DPP. In open-ended responses, providers requested more nutrition counseling and an improved DPP referral process; patients also requested nutrition counseling and classes. Conclusions: Providers and patients saw prediabetes as important but reported knowledge and management gaps, particularly for metformin and DPP, and requested additional practice resources.

Human Papilloma Virus Vaccination.

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide causing a variety of benign and malignant conditions. A significant portion of the global population is infected with HPV, with the virus attributed to causing up to 5% of cancers worldwide. Bivalent, quadrivalent, and nine-valent vaccinations exist to aid in the prevention of these diseases and have been proven to be effective at preventing both benign and malignant disease. While vaccination is readily accessible in more developed countries, barriers exist to worldwide distribution and acceptance of vaccination. Vaccination and screening of HPV infection when used in combination are proven and predicted to decrease HPV related pathology. Improvements in vaccination formulations, for treatment as well as prevention, are actively being sought from a variety of mechanisms. Despite these advancements, and the data supporting their efficacy, there has been substantial delay in obtaining adequate vaccination coverage. In reviewing these challenges and looking forward to new vaccine development-especially within the current pandemic-it is clear from the challenges of HPV we require methods to more effectively encourage vaccination, ways to dispel vaccination myths as they occur, and implement better processes for vaccine distribution globally.

Human Papillomavirus Vaccination Rates of Military and Civilian Male Respondents to the Behavioral Risk Factors Surveillance System Between 2013 and 2015.

OBJECTIVE: To evaluate human papillomavirus (HPV) vaccination rates among men in the USA and to compare vaccination rates among men who had served in the military to those reporting no previous military service. METHODS: We performed a cross-sectional analysis using Behavioral Risk Factor Surveillance System (BRFSS) data from the 2013 to 2015 to analyze HPV vaccination rates for vaccine eligible adult men. The BRFSS is a multistage, cross-sectional telephone survey conducted nationally by state health departments. Univariable and logistic regression analyses were performed to examine the relationship between military service and HPV vaccination status was assessed as well as the number of HPV vaccination doses received. RESULTS: A total of 5,274 participants were analyzed representing a weighted estimate of 1.5 million HPV vaccine eligible men in the USA. The vaccination rate among veterans was 25.3% (95% confidence interval (CI), 18.8-33.3%) compared to 15.9% (95% CI, 14.3-17.6%) for civilians (p < 0.01). Veterans were more likely to report having received at least one dose of the HPV vaccine compared to civilian men (adjusted odds ratios [aOR] = 2.7, 95% CI, 1.7%-4.1%, p < 0.001). CONCLUSIONS: Veteran men are more likely to have received HPV vaccination than similarly aged civilian men. However, for both civilians and veterans, the HPV vaccination coverage remains low when compared to their female counterparts.

Tobacco Use and Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs Between 2009 and 2014.

OBJECTIVE: To evaluate relationships between an objective biomarker of current tobacco exposure and high-risk genital human papillomavirus (HPV) prevalence among adult women in the United States. METHODS: We performed a retrospective analysis of adult women (aged 18-59 years) using three consecutive 2-year cycles (2009-2014) from the cross-sectional National Health and Nutrition Examination Surveys. Women who provided self-collected cervicovaginal swabs and serum were included. Human papillomavirus genotyping was conducted on cervicovaginal samples with a Linear Array HPV assay. Cotinine, a major metabolite of nicotine, was assayed from serum to provide a biomarker of recent tobacco exposure. Participants were stratified into three levels of tobacco exposure (nonsmokers, secondhand smoke exposure, and smokers) based on serum cotinine concentration levels using previously published ethnic-specific cut points. Weighted percentages are provided to account for unequal selection probabilities among participants and adjustments for nonresponse. RESULTS: Among the 5,158 women analyzed, 2,778 were classified as nonsmokers (57.1%, 95% CI 54.5-59.6%), 1,109 classified as having secondhand smoke exposure (18.4%, 95% CI 16.5-20.3%), and 1,271 classified as smokers (24.6%, 95% CI 22.8-26.5%) using serum cotinine concentration levels. Prevalence of HPV infection differed between nicotine exposure groups (P<.001): 441 smokers (32.1%, 95% CI 29.6-34.7%), 322 women with secondhand smoke exposure (26.1%, 95% CI 22.7-29.7%), and 451 nonsmokers (15.1%, 95% CI 13.3-17.1%) had a high-risk genital HPV infection. Controlling for demographics and number of lifetime sexual partners, the risks compared with nonsmokers for infection with a high-risk HPV genotype for smokers (adjusted odds ratio [OR] 1.7, 95% CI 1.4-22) and secondhand smokers (adjusted OR 1.4, 95% CI 1.1-1.8) are similarly increased (P<.001). CONCLUSION: In this large cross-sectional, population-based study, we show a relationship between an objective biomarker of current tobacco use and genital HPV infection. Cigarette smoking and exposure to secondhand smoke are associated with increased odds of infection with high-risk genital HPV independent of lifetime number of sexual partners.

Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.

Prevalence of Genital Human Papillomavirus Infection and Human Papillomavirus Vaccination Rates Among US Adult Men: National Health and Nutrition Examination Survey (NHANES) 2013-2014.

IMPORTANCE: Human papillomavirus (HPV) is a common sexually transmitted infection that is a major cause of noncervical anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for primary prevention. However, the population prevalence data for male genital HPV infection is not well known, while the HPV vaccination coverage is low in the United States. OBJECTIVES: To estimate the prevalence of genital HPV infection and the HPV vaccination rate in the United States among adult men and to examine potential risk factors for HPV infection. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) samples a representative cross-section of the US population. Men aged 18 to 59 years were examined in mobile examination centers during the NHANES 2013-2014. DNA was extracted from self-collected penile swab specimens, and HPV genotyping was performed by polymerase chain reaction amplification. Demographic and vaccination information was gathered via self-report during home-based standardized interviews. Binary multivariable logistic regression was used to estimate the odds of HPV infection. MAIN OUTCOMES AND MEASURES: The prevalence of genital HPV infection and the HPV vaccination coverage rate among adult men. RESULTS: During the NHANES 2013-2014, a total of 1868 men aged 18 to 59 years were examined. The overall genital HPV infection prevalence was 45.2% (95% CI, 41.3%-49.3%). The infection prevalence with at least 1 high-risk HPV subtype defined by DNA testing was 25.1% (95% CI, 23.0%-27.3%). In vaccine-eligible men, the prevalence of infection with at least 1 HPV strain targeted by the HPV 4-valent vaccine and HPV 9-valent vaccine was 7.1% (95% CI, 5.1%-9.5%) and 15.4% (95% CI, 11.7%-19.6%), respectively. Among vaccine-eligible men, the HPV vaccination coverage was 10.7% (95% CI, 7.8%-14.6%). CONCLUSIONS AND RELEVANCE: Among men aged 18 to 59 years in the United States, the overall prevalence of genital HPV infection was 45.2% (95% CI, 41.3%-49.3%). The overall genital HPV infection prevalence appears to be widespread among all age groups of men, and the HPV vaccination coverage is low.

Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs in Young Women in the United States Between 2003 and 2012.

OBJECTIVE: To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women. METHODS: We performed a retrospective review of prevalence data for women aged 18-29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003-2004) and 1,526 from the postvaccine era (2007-2012) were analyzed. RESULTS: Among women aged 18-29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1-13.8%) in the prevaccine era to 4.2% (95% CI 3.3-10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1-13.8%) to 8.8% (95% CI 5.6-12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18-29 years as of 2011-2012. CONCLUSION: Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.

Postcoital bleeding: a review on etiology, diagnosis, and management.

Postcoital bleeding refers to spotting or bleeding that occurs after intercourse and is not related to menstruation. The prevalence of postcoital bleeding ranges from 0.7 to 9.0 percent of menstruating women. There are multiple etiologies for this common complaint in which most are benign such as cervicitis or cervical polyps. However, the most serious cause of postcoital bleeding is cervical cancer. There are currently no recommendations from governing bodies such as the American College of Obstetricians and Gynecologists on evaluating and treating women with postcoital bleeding. The purpose of this paper is to discuss the common causes of postcoital bleeding, the etiologies of postcoital bleeding, and the likelihood that malignancy is the underlying cause. After an extensive literature review, we compiled a paper illustrating the key concepts a practitioner should know when it comes to postcoital bleeding. Finally, this review will conclude with treatment options for women who are found to have an identifiable source for their bleeding and a discussion on the natural history of postcoital bleeding in women who are found to have no identifiable etiology on evaluation.

Paracrine SLPI secretion upregulates MMP-9 transcription and secretion in ovarian cancer cells.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) is amplified in serous ovarian cancer. We have dissected its function, showing it is a survival factor for ovarian cancer and promotes tumorigenesis and paclitaxel-resistance. We hypothesized that the protease inhibitory function was responsible for modulating SLPI's invasive capacity. METHODS: Stable HEYA8 ovarian cancer transfectants expressing vector, wild type SLPI, and protease inhibitor null (F-)SLPI were examined in vitro and in xenografts. Invasion, enzyme activity, and MMP production and function assays were applied. SLPI and MMP immunoexpression was graded on tissue microarray and clinical samples. Statistical comparisons used unpaired t test and ANOVA, where appropriate. RESULTS: SLPI and F-SLPI cells caused greater parenchymal and peritoneal dissemination over control cells in xenografts and invasion assays (p<0.001). MMP-9 protease activity was increased in SLPI and F-SLPI cells over control. SLPI, but not F-SLPI, inhibited plasmin activity, necessary for MMP-9 activation and release, and inhibited activation of MMP-9. However, paradoxically, both induced quantitative MMP-9 transcription (p<0.05) and protein (p<0.008), yielding an increased net MMP-9 activity in the face of plasmin inhibition. SLPI and MMP-9 expression were strongly correlated in serous ovarian cancers (r(2)=0.986) and a set of ovarian cancers (p<0.02). SLPI expression was greater in serous than endometrioid ovarian cancers (p=0.04). CONCLUSIONS: SLPI stimulates ovarian cancer invasion, modulated in part by its serine protease inhibitory activity attenuating MMP-9 release. However, SLPI induction of MMP-9, independent of protease inhibition activity, is greater yielding a net pro-invasive behavior. These findings further support SLPI as a molecular target for ovarian cancer.

Proteomics and biomarkers in clinical trials for drug development.

Proteomics allows characterization of protein structure and function, protein-protein interactions, and peptide modifications. It has given us insight into the perturbations of signaling pathways within tumor cells and has improved the discovery of new therapeutic targets and possible indicators of response to and duration of therapy. The discovery, verification, and validation of novel biomarkers are critical in streamlining clinical development of targeted compounds, and directing rational treatments for patients whose tumors are dependent upon select signaling pathways. Studies are now underway in many diseases to examine the immune or inflammatory proteome, vascular proteome, cancer or disease proteome, and other subsets of the specific pathology microenvironment. Successful assay verification and biological validation of such biomarkers will speed development of potential agents to targetable dominant pathways and lead to selection of individuals most likely to benefit. Reconsideration of analytical and clinical trials methods for acquisition, examination, and translation of proteomics data must occur before we march further into future of drug development.

The value of repeated cytology at the time of first colposcopy: a retrospective analysis of 1,087 cases.

Papanicolaou tests are often repeated just before the procedure for women who have been referred for colposcopy. The validity and clinical usefulness of this practice, however, is unclear. We retrospectively assessed the value of repeated cytology in a cohort of 1,087 consecutive patients who underwent repeated Papanicolaou testing at first colposcopy. The repeated cytology was considered clinically useful if the results could conceivably have influenced the physician's decision about more invasive diagnostic/therapeutic evaluation based on contemporary practice guidelines. Repeated cytology provided potentially clinically useful information in only a small proportion (3.6%) of the cases analyzed overall, including 41% (26/63) and 1.8% of the high- and low-grade squamous intraepithelial lesions referral cytology cases, respectively. Our data indicate that repeated cytology provides potentially clinically useful information in only a small percentage of overall cases but a substantial proportion of high-grade squamous intraepithelial lesion referral cytology cases, suggesting that high-risk referral cytology case subsets can be defined wherein the routine performance of repeated cytology would be most efficacious.

Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers.

OBJECTIVE: There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC. METHOD: PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors. RESULTS: Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P<0.0001) and OS (P<0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC=0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model. CONCLUSIONS: We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.