Integrating a Systematic, Comprehensive E-Cigarette and Vaping Assessment Tool into the Electronic Health Record.

BACKGROUND: Recently, the use of electronic cigarettes increased sharply, leading to increased e-cigarette, or Vaping Product Use-Associated Lung Injury (EVALI), and other acute pulmonary conditions. There is an urgent need for clinical information about e-cigarette users to identify factors that contribute to EVALI. We developed an e-cigarette/vaping assessment tool (EVAT) that was integrated into the Electronic Health Record (EHR) of a large state-wide medical system and initiated a system-wide dissemination and education to support its use. METHODS: EVAT documented current vaping status, history, and e-cigarette content (nicotine, cannabinoids, and/or flavoring). Educational materials and presentations were developed via a comprehensive literature review. EVAT utilization in the EHR was assessed quarterly. Patients' demographic data and clinical site name were also collected. RESULTS: The EVAT was built, validated, and integrated with the EHR in July 2020. Live and virtual seminars were conducted for prescribing providers and clinical staff. Asynchronous training was offered using podcasts, e-mails, and Epic tip sheets. Participants were informed about vaping harm and EVALI and instructed on the use of EVAT. As of December 31, 2022, EVAT was used 988,181 times, with 376,559 unique patients evaluated. Overall, 1,063 hospital units and affiliated ambulatory clinics used EVAT, including 64 Primary Care, 95 Pediatrics, and 874 Specialty sites. CONCLUSIONS: EVAT was successfully implemented. Continued outreach efforts are needed to further increase its usage. Education materials should be enhanced to help providers to reach youth and vulnerable populations and connect patients to the tobacco treatment resources.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90). CONCLUSIONS: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3.

Patient Engagement by the Tobacco Quitline After Electronic Referrals.

INTRODUCTION: Referrals through the electronic health record (EHR) system provide an efficient evidence-based method to connect patients to the Tobacco Quitline. However, patients frequently do not respond to Quitline phone calls or accept services. The goal of this study was to characterize factors associated with successful engagement with Quitline following e-referrals by physicians in Maryland. AIMS AND METHODS: This is a cross-sectional study with hierarchical data modeling. Data for 1790 patients e-referred in 2018-2019 by the University of Maryland Medical System (UMMS) were analyzed. Patients' engagement was assessed using a generalized estimating equation multivariable regression model for ordinal outcomes at two levels: Picking up a phone call from Quitline (1-800-QUIT-NOW) and enrollment in tobacco cessation programs. RESULTS: Older age, female gender, black race, low socioeconomic status, and provider's skills were significantly associated with successful outcomes of Quitline referral. The engagement with Quitline was higher in black non-Hispanic patients compared to other racial/ethnic groups (phone call response odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.35% to 2.93% and service acceptance OR = 1.89, 95% CI = 1.28% to 2.79%). Patients residing in socioeconomically deprived areas were more likely to respond to Quitline phone calls compared to those from affluent neighborhoods (OR = 1.52, 95% CI = 1.03% to 2.25%). Patients referred by faculty or attending physicians were more likely to respond compared to those referred by residents (OR = 1.23, 95% CI 1.04, 1.44, p = .0141). CONCLUSIONS: Multiple factors impact successful engagement with Quitline. Additional means to improve Quitline engagement success may include focused messaging on tobacco cessation benefits to patients, and skillful counseling by the provider. IMPLICATIONS: Implementation of the clinical decision support (CDS) tool for electronic referrals to the Tobacco Quitline at the UMMS was successful in providing evidence-based free service to elderly patients and socioeconomically disadvantaged racial and ethnic minorities. The CDS also served to engage physicians in conversation about tobacco use and cessation with every tobacco-using patient. Curricular content for physicians in training should be enriched to expand tobacco use and treatment.

Electronic referrals to the tobacco Quitline: implementation strategies in a large health system to optimize delivery of tobacco cessation to patients.

Electronic referrals provide an efficient solution for clinicians to connect patients to free tobacco cessation services, such as the tobacco Quitline. However, strategic planning is necessary for the successful adoption of this method across the health care system. The purpose of this study was to develop an implementation strategy for electronic referrals to the tobacco Quitline in a large health system. A clinical decision support tool created a closed-loop e-referral pathway between the electronic health record system and the Quitline. Multilevel strategies were developed to implement the e-referral process across the entire health system, including leadership buy-in, Epic tip sheets, newsletters, training for practice champions and staff, physician educator, patient-focused advertisements, and video clips distribution by the Maryland Department of Health Center for Tobacco Prevention and Control. The implementation of a system-wide e-referral pathway for tobacco cessation involved continuous clinician education and training, systematic quality control, and engaging "champion" clinicians. Postimplementation data analysis revealed that 1,790 e-referrals were received by the Quitline in 2018-2019, of which 18% accepted follow-up services, 18% declined, and 64% were not reached after multiple attempts. Among 322 patients who accepted Quitline services, 55% requested nicotine replacement therapy. Overall, 282 clinicians referred patients, including 107 primary care physicians and 175 specialists; 62 clinicians e-referred 72% patients, thereby emerging as "tobacco champions." The e-referral process is an efficient method for tobacco users to receive a cessation referral from clinicians. Sustainability can be achieved through leadership buy-in, physician ease of use, patient motivation, information technology supports, and reminders.

Community Awareness of HPV Screening and Vaccination in Odisha.

Introduction. A number of new technologies including cervical cancer screening and vaccination have introduced new tools in the fight against cervical cancer. Methods. This study was set in Odisha, India, at the Acharya Harihar Regional Cancer Center and study research infrastructure at the Asian Institute of Public Health. IRB approvals were obtained and a research assistant recruited 286 women aged 18-49 years, who provided informed consent and completed a survey tool. Data were entered into EpiData software and statistical analysis was conducted. Results. 76.3% women participants were married, 45.5% had sexual debut at age 21 or greater, 60.5% used contraception, 12.2% reported having a Pap smear in the past, and 4.9% reported having prior genital warts. Most, 68.8% had never heard of HPV and 11.9% were aware that HPV is the main cause of cervical cancer. 82.9% women thought that vaccinations prevent disease, and 74.8% said they make the decision to vaccinate their children. Conclusion. The Odisha community demonstrated a low level of knowledge about cervical cancer prevention, accepted vaccinations in the prevention of disease and screening, and identified mothers/guardians as the key family contacts.

Phase I clinical trial of repeat dose terameprocol vaginal ointment in healthy female volunteers.

OBJECTIVES: This safety study of terameprocol (also called M4N, EM-1421) daily vaginal application in healthy women explores its potential application as a microbicide in interrupting human immunodeficiency virus sexual transmission and additional interruption of human papillomavirus and herpes simplex virus transmission. METHODS: A double-blind placebo controlled phase I repeat dose tolerability and pharmacokinetic, crossover study of 90 mg terameprocol (2% w/w ointment) administered intravaginally for 7 consecutive days in healthy female subjects. The pharmacokinetics after administration was examined on days 1 and 7 of dosing. Subjects underwent vaginal examination following the 6-hour pharmacokinetic sample on day 7 of each study period. RESULTS: Recruitment started January 2006 and ended May 2006, and 14 subjects completed the study. Median age was 24 years. No treatment-related serious adverse events were reported, and there were a total of 17 treatment-emergent adverse events (AE) reported by 11 participants. The most common AE was headache. Terameprocol was not detectable in serum in pharmacokinetic samples. CONCLUSIONS: Terameprocol was well tolerated at a 90 mg dose (2% wt/wt) administered vaginally daily for 7 days. No serious adverse events occurred and any AEs were mild. The excellent safety profile supports future clinical trial to evaluate the application of intravaginal terameprocol in women.

Human papillomavirus vaccine and cervical cancer prevention: practice and policy implications for pharmacists.

OBJECTIVES: To review the epidemiology and natural history of human papillomavirus (HPV), summarize relevant clinical trials of the prophylactic HPV vaccines, and describe the practice and policy implications that HPV vaccine represents for pharmacists. DATA SOURCES: Search of Medline through June 2007 using keywords human papillomavirus vaccine, Gardasil, and Cervarix; meeting abstracts; bibliographies from selected articles; and National Institutes of Health clinical trials registry. STUDY SELECTION: English language review articles, clinical trials, and published abstracts were considered for inclusion. DATA SYNTHESIS: HPV is a sexually transmitted infection that is necessary for the development of cervical cancer, and types 16 and 18 are associated with 70% of cases of invasive cervical cancer worldwide. A quadrivalent prophylactic vaccine against HPV-6, -11, -16, and -18 is currently available, and a bivalent vaccine targeting HPV-16 and -18 is under review by the Food and Drug Administration. Both are highly effective at preventing persistent HPV infection and precancerous lesions caused by vaccine-specific HPV. HPV vaccine is currently indicated for girls aged 9 to 26 years, but ongoing trials are evaluating the efficacy in other populations. Implementation of a vaccine administration program is an area of opportunity for new policies to include pharmacists in the administration of prophylactic HPV vaccines. Pharmacists are allowed to administer vaccinations in 46 states and can potentially play a role in HPV vaccine administration. For this to happen, however, multiple legal and regulatory changes must occur. CONCLUSION: Prophylactic HPV vaccines safely and effectively prevent HPV infection and precancerous lesions in the cervix. The availability of these vaccines also create new clinical opportunities for community pharmacists, provided needed legal, regulatory, and policy changes are made.

Phase I/II clinical safety studies of terameprocol vaginal ointment.

OBJECTIVES: Terameprocol (M4N, EM-1421) is a novel transcription inhibitor that selectively interferes with HPV viral genes E6/E7 with Sp1-dependent promoters, and induces apoptosis by inactivation of the CDC2/cyclin B complex (maturation promoting factor) and production and phosphorylation of survivin. This trial was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity and determine the pharmacokinetic profiles of intravaginal terameprocol in women with HPV-linked cervical squamous intraepithelial neoplasia. METHODS: An open label, dose escalation Phase I/II clinical trial enrolled women with biopsy confirmed CIN 1, 2 or 3. Terameprocol (45 or 90 mg) was physician-administered directly to the cervix uteri in 3 once weekly applications. The pharmacokinetics after administration were examined on Day 1 of dosing. Patients underwent colposcopic examinations, HPV testing, biomarker assessments, cytology and cervical punch biopsy. RESULTS: Recruitment ended March 30, 2006 and 7 patients were enrolled. Median age was 24 years. There were no serious adverse events (SAEs) and possible treatment-related Adverse Events (AEs) reported were mild and self-limiting. There was no detectable absorption of terameprocol from the vaginal ointment application. CONCLUSIONS: Terameprocol in 1% and 2% vaginal ointment use in Phase I/II trials with women with HPV-linked cervical intraepithelial neoplasia has an excellent safety profile, no SAEs reported and mild, self-limiting treatment-related AEs. There was no detectable absorption of terameprocol. These data support the continued evaluation of terameprocol in in vitro and animal efficacy models followed by definitive human Phase II clinical trials in CIN.

Genital dysplasia in women infected with human immunodeficiency virus.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) are at increased risk for the development of dysplastic genital lesions. Traditionally, markers of immunosuppression were predictive of the development of dysplasia. Recent advances in antiretroviral medications allow restoration of a once-depressed CD4+ cell count and suppression of HIV replication. In this new era, additional predictive markers of genital dysplasia are needed for management of women infected with with HIV. OBJECTIVE: To find predictive markers of genital dysplasia in women infected with HIV. DESIGN: Observational study of a consecutive sample of 200 women infected with HIV from an urban university clinic. Measurements of histopathology, CD4+ count, CD4+ nadir, HIV viral load, human papillomavirus (HPV), and usage of highly active antiretroviral therapy (HAART) were evaluated for an association with genital dysplasia. RESULTS: There was a trend toward a protective effect against any genital dysplasia when HAART had been prescribed [relative risk = 0.77, 95% confidence interval (CI) 0.56, 1.06] and HAART therapy resulted in an immune response (relative risk, 0.61; 95% CI, 36, 1.02). High-risk HPV DNA was a strong predictor of dysplasia (P =.0003). A lower CD4+ count nadir was strongly associated with genital dysplasia (P =.0003). CONCLUSION: A history of greater immunosuppression, as measured by the nadir of a patient's CD4+ count, is the strongest predictor of genital dysplasia in women infected with HIV.

Early detection and screening for ovarian cancer: does physician specialty matter?

OBJECTIVE: To examine physician factors associated with ovarian cancer screening. METHODS: Postal questionnaires to Maryland primary care physicians. Bivariate tests for statistical significance used X-Square and Student's t tests. Multivariate analysis and logistic regression were used to analyze responses based on specialty type, gender, and work experience. RESULTS: Fifty-six percent of the 375 were male, 44%, females; 33%, OB/GYN; and 67%, family/internal medicine (FM/IM). The mean age was 47 and the mean number of years in practice was 16. OB/GYNs provided more ovarian cancer counseling, OR 2.64 (CI 1.55, 4.48) and were more likely to respond correctly to knowledge questions--i.e., reduction of ovarian cancer risk with oral contraceptive (OCP) use than IM/FM, OR 8.57 (CI 3.54, 20.8). Overall, there were few gender differences in approach to evaluation, but male physicians were less likely to be aware of the relationship of OCP use to ovarian cancer risk than females, OR 0.48 (CI 0.25, 0.91). IF/FM physicians were less likely to order CA-125 for patients (of any age) based upon symptoms of bloating or physical examination alone. OB/GYN physicians, OR 4.77 (2.73, 8.34) and physicians with > 15 years in practice, OR 2.79 (1.46, 5.35) attended more meetings on ovarian cancer than non OB/GYNs or those with less experience. Although 74% indicated access to the Internet, just 16% to 26% used the Internet for cancer information; OB/GYNs used the Internet less frequently than FM/IMs, OR 0.53 (0.28, 0.97). CONCLUSIONS: Specialty was more predictive of knowledge, approach to evaluation, and counseling than gender or experience.

HAART use in women with HIV and influence on cervical intraepithelial neoplasia: a clinical opinion.

OBJECTIVES: Study the role of highly active antiretroviral therapy (HAART) in cervical disease in women with human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. MATERIALS AND METHODS: A systematic review of current literature and the results summarized in the following headings: HIV and cytological evidence of disease, HIV and HPV, and HAART and HIV in women with HPV-associated cervical disease. RESULTS: Limited data is available to study the influence of HAART on HPV-related cervical disease in women with HIV. There is evidence that the use of HAART may lead to immune restoration and thereby prevent severe recurrent HPV disease, thus influencing associated cervical disease. CONCLUSIONS: Little data is available on HAART and its role in HPV-associated cervical disease in women with HIV. Immune restoration may decrease the severity and recurrence of HPV infection and potentially impact cervical disease. Population-based studies are needed to further evaluate the role of HAART in HPV associated cervical disease.