COVID-19 vaccine uptake among non-US-born populations in the United States, 2020-2022.

BACKGROUND: In the United States (US), COVID-19 vaccination rates among non-US-born individuals (i.e., refugees, immigrants, and migrants [RIM]) are variable. Understanding baseline COVID-19 vaccine coverage among these populations and determining if disparities exist is essential for quality improvement initiatives and public health interventions. METHODS: Baseline COVID-19 vaccination rates for both primary series and booster doses were calculated at four health systems located in Minnesota, Colorado, and Pennsylvania participating in the Minnesota Department of Health's Center of Excellence in Newcomer Health. Patients aged ≥5 years as of 1/1/22, seen for ≥1 primary care visit during 7/1/2019-6/30/22 were included. Descriptive statistics were calculated for three measures of COVID-19 vaccine coverage during 12/14/2020-6/30/2022: 1) initiation of primary series; 2) completion of primary series; 3) completion of first booster. We calculated vaccine coverage rates for the entire population and stratified by subgroup including country of origin, refugee status, and primary language preference. RESULTS: We included 1,624,573 patients eligible for COVID-19 primary series vaccine and 907,749 eligible for COVID-19 booster vaccination. The percent of eligible patients who completed a COVID-19 primary series (63.4 %) and booster dose (66.2 %) were similar. Completion of the primary series was higher for non-US-born persons (72.7 %) compared with US born persons (65.4 %), similar among refugees (63.5 %) and non-refugees (63.4 %), and lower in patients with language preference other than English (62.7 %) compared with English preferring patients (63.6 %). Booster completion was lower for non-US-born persons (61.8 %), refugees (46.7 %), and patients with language preference other than English (55.3 %) compared with US-born (70 %), non-refugees (66.3 %), and English preferring patients (67.3 %) respectively. CONCLUSIONS: This evaluation identified disparities in COVID-19 vaccination rates among non-US-born persons and persons with a language preference other than English living in the US. Targeted outreach efforts may be beneficial in reaching these populations.

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis.

BACKGROUND: Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible. METHOD: Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline's impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans. RESULTS: Fifty studies met the inclusion criteria: 33 assessed bedaquiline's impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline's efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection. CONCLUSIONS: Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. AIMS AND METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. CONCLUSIONS: The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Integrating Tobacco Treatment Into Oncology Care: Reach and Effectiveness of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers.

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness. METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified as currently smoking who received at least one evidence-based tobacco treatment component (eg, counseling and pharmacotherapy)-and smoking cessation effectiveness (effectiveness)-the proportion of patients reporting 7-day point prevalence abstinence at 6-month follow-up. Center-level differences in reach and effectiveness were examined by center characteristics, implementation strategies, and tobacco treatment components. RESULTS: Of the total 692,662 unique patients seen, 44,437 reported current smoking. Across centers, a median of 96% of patients were screened for tobacco use, median smoking prevalence was 7.4%, median reach was 15.4%, and median effectiveness was 18.4%. Center-level characteristics associated with higher reach included higher smoking prevalence, use of center-wide TTP, and lower patient-to-tobacco treatment specialist ratio. Higher effectiveness was observed at centers that served a larger overall population and population of patients who smoke, reported a higher smoking prevalence, and/or offered electronic health record referrals via a closed-loop system. CONCLUSION: Whole-center TTP implementation among inpatients and outpatients, and increasing staff-to-patient ratios may improve TTP reach. Designating personnel with tobacco treatment expertise and resources to increase tobacco treatment dose or intensity may improve smoking cessation effectiveness.

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.

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.

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems.

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. RESULTS AND SIGNIFICANCE: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. CONCLUSIONS: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Operationalizing Leadership and Clinician Buy-In to Implement Evidence-Based Tobacco Treatment Programs in Routine Oncology Care: A Mixed-Method Study of the U.S. Cancer Center Cessation Initiative.

BACKGROUND: Delivering evidence-based tobacco dependence treatment in oncology settings improves smoking abstinence and cancer outcomes. Leadership engagement/buy-in is critical for implementation success, but few studies have defined buy-in or described how to secure buy-in for tobacco treatment programs (TTPs) in cancer care. This study examines buy-in during the establishment of tobacco treatment programs at National Cancer Institute (NCI)-designated cancer centers. METHODS: We utilized a sequential, explanatory mixed-methods approach to analyze quantitative data and qualitative interviews with program leads in the U.S.-based NCI Moonshot-supported Cancer Center Cessation Initiative (n = 20 Centers). We calculated descriptive statistics and applied structural coding and content analysis to qualitative data. RESULTS: At least 75% of participating centers secured health care system administrative, clinical, and IT leadership buy-in and support. Six themes emerged from interviews: engaging leadership, access to resources, leveraging federal funding support to build leadership interest, designating champions, identifying training needs, and ensuring staff roles and IT systems support workflows. CONCLUSIONS: Buy-in among staff and clinicians is defined by the belief that the TTP is necessary, valuable, and evidence based. Recognizing and securing these dimensions of buy-in can facilitate implementation success, leading to improved cancer outcomes.

Identification of the blue light intensity administered to one eye required to suppress bovine plasma melatonin and investigation into effects on milk production in grazing dairy cows.

Long-day photoperiod is known to positively affect milk production in confinement dairy systems, and it has been hypothesized that pineal melatonin (MT) secretion plays a substantial role in this process. Specialized mammalian photoreceptors that regulate MT secretion are optimally stimulated by short wavelength blue light. We investigated the blue light intensity administered to one eye required to suppress MT secretion in nonlactating dairy cows, and subsequently examined effects on milk production in grazing dairy cows. Following a 14-d light-dark 8:16 h environmental conditioning period, 5 nonlactating Holstein-Friesian cows were exposed to treatments of <1, 70, 125, 175, and 225 lx for 8 additional hours using a 5 × 5 Latin square design. Light was administered via headpieces fitted with light-emitting diodes emitting blue light (465 nm) to the right eye. All cows were then exposed to a light-dark 16:8 h cycle for one night via the indoor lighting system (>200 lx white light). Plasma samples collected at regular intervals were assayed for MT. A dose-dependent effect of light treatment on mean circulating MT concentrations (and 95% CI) was observed [9.4 (7.2, 12.3), 5.0 (3.8, 6.6), 4.4 (3.3, 5.7), 3.3 (2.5, 4.3) and 1.7 (1.3, 2.3) pg/mL for treatments of 0, 70, 125, 175, and 225 lx, respectively. Only the 225 lx treatment acutely suppressed plasma melatonin concentration to levels similar to the light-dark 16:8 h treatment [1.9 (1.4, 2.5) pg/mL]. Forty spring-calving cows were blocked on parity, calving date and Economic Breeding Index for milk production and assigned to the control treatment or blue light to a single eye (LT) treatment from calving through 32 wk of lactation. The cows assigned to LT treatment were fitted with headpieces providing 225 lx of blue light to the right eye from 1700 until 0000 h. Mean milk production (and 95% CI) during 32 wk of lactation was not affected by treatment [20.3 (19.3, 21.3) vs. 20.9 (19.8, 22.0) kg/d, control and LT, respectively]. Within multiparous cows, a treatment by week interaction was detected, whereby LT treatment increased milk production during the first 12 wk of lactation [25.8 (24.3, 27.3) vs. 28.0 (26.5, 29.5) kg/d; +8.5%], but had no effect thereafter. Treatment did not affect plasma insulin-like growth factor 1. We identified the blue light intensity to one eye required to acutely suppress MT concentrations. Transient favorable effects on milk production were observed in multiparous cows. It remains unclear how single-eye blue light treatment affects galactopoiesis in grazing dairy cows, and further research is needed to explore whether this modality of light delivery represents a useful means to aid productivity in pasture-based dairy systems.

Overcoming Barriers: Evidence-Based Strategies to Increase Enrollment of Underrepresented Populations in Cancer Therapeutic Clinical Trials-a Narrative Review.

Disparities in cancer incidence and mortality rates among racial and ethnic minorities (African Americans, Asian Americans, Pacific Islanders, American Indians, and Latinos/Hispanic Americans) in the USA are well documented. Enrollment of underrepresented populations in cancer therapeutic clinical trials, however, is very low. This is true despite federal mandates to ensure accrual rates adequate for analyses and the evidence that the effectiveness of specific therapies and medications varies across ethnic and racial groups. Consequently, cancer clinical decision-making is based on research studies where the majority of research participants are white males, despite the disproportionate cancer burden in racial and ethnic minority groups. To date, there have been multiple reviews detailing the barriers to enrollment for these populations in cancer clinical trials, but a notable lack of research on possible strategies to overcome them. The aim of this narrative review is to summarize the current evidence for effective approaches to increase enrollment of underrepresented minorities in cancer therapeutic clinical trials. These approaches include (1) cultural and linguistic adaptations of marketing materials, (2) the use of patient navigators, and (3) building ongoing community partnerships. The majority of studies reviewed employ multiple improvement strategies simultaneously. Identifying effective approaches to increase enrollment of underrepresented populations in cancer clinical trials is a critical step in reducing persistent disparities in cancer incidence and mortality among racial and ethnic populations.

Association between smoking cessation and post-hospitalization healthcare costs: a matched cohort analysis.

BACKGROUND: The potential economic benefit in terms of reduced healthcare costs when patients quit smoking after hospital discharge has not been directly measured. The aim of this study was to compare the costs for hospital admission and six-month follow-up for a cohort of patients who self-reported abstinence from cigarettes at 6 months after hospital discharge and a matched group of patients who reported continued smoking. MATERIALS AND METHODS: This was a secondary analysis of a recent population-based clinical trial cohort (ClinicalTrials.gov ID: NCT01575145), with cohort membership determined by self-reported 7 day point prevalence abstinence at 6 months after the index hospital discharge. Participants were admitted to Mayo Clinic Hospital, Rochester, MN, between May 5, 2012 and August 10, 2014 for any indication and lived in the areas covered by postal codes included in Olmsted County, MN. Propensity score matching was used to control for differences between groups other than smoking status, and any residual imbalance was adjusted through generalized linear model with gamma distribution for cost and log-link transformation. RESULTS: Of 600 patients enrolled in the clinical trial, 144 could be contacted and self-reported 7 day point prevalence abstinence at 6 months after hospital discharge. Of these patients, 99 were successfully matched for this analysis. The cost for the index hospitalization was significantly greater in patients who abstained compared to those that did not abstain (mean difference of $3042, higher for abstainers, 95% CI $170 to $5913, P = 0.038). However, there was no difference between mean 6-month follow-up costs, number of inpatient hospitalizations, or number of emergency room visits for abstainers versus non-abstainers. CONCLUSION: There was no evidence to support the hypothesis that abstinence at 6 months after hospital discharge is associated with a decrease in health care costs or utilization over the first 6 months after hospital discharge.

Feasibility of a Perioperative Text Messaging Smoking Cessation Program for Surgical Patients.

Although surgical patients who smoke could benefit from perioperative abstinence, few currently receive support. This pilot study determined the feasibility and acceptability of a perioperative text messaging smoking cessation program. One hundred patients (73% of eligible patients approached) enrolled in a surgery-specific messaging service, receiving 1-3 daily messages about smoking and surgical recovery for 30 days. Only 17 patients unenrolled, the majority responded to prompting messages, and satisfaction with the program was high. Surgical patients are amenable to text message-based interventions; a future efficacy trial of text messaging smoking cessation support in surgical patients is warranted.

Researching immunocontraceptive vaccines with mares (Equus caballus) as both a target and model for African elephant (Loxodonta africana) cows: A review.

A sequence of studies is reviewed that reported the domestic horse (Equus caballus) mare as an appropriate and accessible research platform for recording clinical and laboratory data post-immunisation with anti- GnRH and -zona pellucida (ZP) immunocontraceptive vaccines. Experience with a native porcine ZP (pZP) vaccine in African elephant (Loxodonta africana) cows highlighted needs for improving vaccine formulations and more clearly defining associated ovarian effects and safety profiles. Initially, the efficacy, reversibility and safety of the GnRH vaccine Improvac® in mares was demonstrated using reproductive tract ultrasonography and concurrently measuring serum antibody titres and progesterone concentrations. Results informed the study design and minimally invasive monitoring of post-treatment ovarian steroid responses of this vaccine in free-ranging African elephant cows. A subsequent sequence of studies reported reversible contraceptive and immunological efficacy in pony mares immunised with pZP formulated with Freund's adjuvants. By comparison, mares treated with a recombinant ZP3 and ZP4 (reZP) vaccine showed disappointing responses. Unexpectedly, most pZP-treated mares showed ovarian inactivity. In attempting to understand this response, results showed the involvement of cytotoxic (CD8+) T-cells negatively correlated to serum ovarian steroid and anti-Müllerian hormone (AMH) levels. Of concern was the prevalence of injection-site lesions ascribable to Freund's adjuvants. Following this, mares treated with both pZP and a novel reZP vaccine formulated with non-Freund's adjuvants showed comparable immunological responses and ovarian inactivity, notably without adverse treatment reactions. In addition, measuring AMH showed promise for monitoring ovarian function in anti-ZP-treated animals.

Serum antibody immunoreactivity and safety of native porcine and recombinant zona pellucida vaccines formulated with a non-Freund's adjuvant in horses.

Commercial and regulatory limitations associated with native porcine zona pellucida (pZP) vaccines formulated with Freund's adjuvants may be overcome by developing effective recombinant ZP vaccines (reZP) and identifying alternative adjuvant formulations. A two-part preparatory study used 15 geldings and identified potentially effective alternative adjuvant formulations based on anti-pZP antibody response following treatment with pZP formulated with Addavax (AddaVax ™, Invivogen), Quil A (Quil-A® Adjuvant, Invivogen), Quil A and Poly (I:C) (HMW VacciGrade™, Invivogen), Pet Gel A (Montanide™ Pet Gel A, Seppic) and Pet Gel A and Poly (I:C). Injection site reactions, rectal temperature and respiratory and heart rates were also monitored for three days post-treatment. Suitable anti-pZP antibody titres were seen in response to Pet Gel A and Pet Gel A and Poly (I:C). Subsequently in 31 mares, following administration of pZP, reZP and a combination of pZP and reZP proteins prepared in Pet Gel A and Poly (I:C), both serum anti-pZP and -reZP antibody responses were monitored. In addition, safety was assessed for up to seven days post-treatment by inspection and palpation of gluteal intramuscular injection sites and measurement of rectal temperature. The measured antibody titres in all treatment groups differed significantly to an adjuvant control group (P < 0.001). Temporal changes in both anti-pZP and -reZP antibody titres in all ZP treatment groups were similar to patterns reported previously in various species vaccinated with pZP formulated with Freund's adjuvants. There were no differences in anti-pZP antibody titres between the pZP and reZP treated groups (P > 0.05). Side effects were mild and transient in nature. This represents the first application of a reZP vaccine formulated with non-Freund's adjuvants evoking a similar antibody titre response to native pZP vaccination in mares.

Economic Analysis of a Geographically Defined Cohort of Hospitalized Patients Who Smoke.

OBJECTIVE: To compare the indications for hospital admission between current, former, and never smokers and to compare their costs per hospital admission, testing the hypothesis that the cost per hospital admission would be higher for smokers than for former and never smokers. PATIENTS AND METHODS: This study used a retrospective nested cohort design, with cohort membership determined by cigarette smoking status (current, former, or never). Propensity score-matching techniques were used to control for differences between groups other than smoking status. Participants were admitted to Mayo Clinic Hospital, Rochester, Minnesota, between May 5, 2012, and August 10, 2014, and lived in the areas covered by postal codes included in Olmsted County, Minnesota. RESULTS: Compared with never smokers, a significantly higher proportion of admissions in current smokers were for diseases of the respiratory system, diseases of the circulatory system, infectious and parasitic diseases, mental illness, and injury or poisoning (P<.001 for all). The average cost per admission (without regard to admission indication) did not depend on smoking status. Accounting for dependence of admission indication on smoking status, there were no significant differences in costs between current and never smokers ($199 less per admission for current smokers; 95% CI -$820 to $423; P=.53) but costs in current smokers were actually significantly less than costs in former smokers (by -$870 per admission; 95% CI, -$1665 to -$76; P=.03). CONCLUSION: There is no evidence that the cost of hospital admission is higher in current smokers than in never or former smokers, even when controlling for admission indication, in a general population of medical and surgical patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01575145.

Ovarian function following immunocontraceptive vaccination of mares using native porcine and recombinant zona pellucida vaccines formulated with a non-Freund's adjuvant and anti-GnRH vaccines.

An important determinant in the selection of any contraceptive agent is the impact on ovarian function, both in the short and longer term. In this study, ovarian activity was monitored in mares immunised with one of the following vaccine formulations; native porcine zona pellucida (pZP), recombinant zona pellucida proteins ZP3 and ZP4 (reZP), pZP and reZP combined or a commercially available anti-GnRH vaccine. The ZP antigens were prepared in an adjuvant formulation consisting of 6% polymeric adjuvant (Montanide™ PetGel A, Seppic, France) and 500 µg polyinosinic-polycytidylic acid - TLR3-agonist (Poly(I:C) HMW VacciGrade™, Invivogen, USA). A vehicle-only control group was administered the adjuvant formulation without antigen. Ovarian activity was monitored using clinical observations (transrectal palpation and ultrasonography of the reproductive tract) in addition to blood sampling for serum progesterone and anti-Müllerian hormone (AMH) concentrations while employing a low sampling frequency. Treatments and measurements were initiated in December (southern hemisphere summer) and subsequent data collection was performed in January, February, March and May. Both reZP and anti-GnRH vaccination were associated with clinically evident ovarian suppression in the short term. Ovarian activity in mares administered a reZP or anti-GnRH vaccine was significantly different to adjuvant control and pZP treated mares. Serum AMH concentrations were different between pZP and anti-GnRH treated mares 3.5 months after the final vaccination. Serum AMH concentrations were significantly correlated with mare age, serum progesterone and ovarian volume.

Tobacco Dependence Treatment Grants: A Collaborative Approach to the Implementation of WHO Tobacco Control Initiatives.

The number of global tobacco-related deaths is projected to increase from about 6 million to 8 million annually by 2030, with more than 80% of these occurring in low- and middle-income countries (LMICs). The World Health Organization Framework Convention on Tobacco Control (FCTC) came into force in 2005 and Article 14 relates specifically to the treatment of tobacco dependence. However, LMICs, in particular, face several barriers to implementing tobacco dependence treatment. This paper is a descriptive evaluation of a novel grant funding mechanism that was initiated in 2014 to address these barriers. Global Bridges. Healthcare Alliance for Tobacco Dependence Treatment aims to create and mobilize a global network of healthcare professionals and organizations dedicated to advancing evidence-based tobacco dependence treatment and advocating for effective tobacco control policy. A 2014 request for proposals (RFP) focused on these goals, particularly in LMICs, where funding for this work had been previously unavailable. 19 grants were awarded by Global Bridges to organizations in low- and middle-income countries across all six WHO regions. Virtually all focused on developing a tobacco dependence treatment curriculum for healthcare providers, while also influencing the political environment for Article 14 implementation. As a direct result of these projects, close to 9,000 healthcare providers have been trained in tobacco dependence treatment and an estimated 150,000 patients have been offered treatment. Because most of these projects are designed with a "train-the-trainer" component, two years of grant funding has been a tremendous catalyst for accelerating change in tobacco dependence treatment practices throughout the world. In order to foster such exponential growth and continue to maintain the impact of these projects, ongoing financial, educational, and professional commitments are required.

Perioperative tobacco use treatments: putting them into practice.

Treatment for tobacco use is efficacious and beneficial to health. Although guidelines recommend that all patients who use tobacco are offered treatment as a part of their clinical care, implementing treatment has proven challenging. In the case of surgical patients, this lack of treatment is particularly unfortunate, as the benefits of abstinence from tobacco are immediate in terms of reducing the risk of surgical complications, including cardiovascular, respiratory, and wound related complications. Surgery also presents an opportunity for patients to quit for good and reduce the long term health risk. This review examines the principles of tobacco use treatment, the rationale for tobacco use treatment in the perioperative period, and how treatment can be incorporated into the routine care of surgical patients. The discipline of implementation science helps to frame these efforts by seeking to better understand how changes in clinical practice occur, and it has the potential to guide an evidence based approach to embedding tobacco treatment into the routine clinical care of surgical patients. This review uses the consolidated framework for implementation research, which includes five major domains, as a representative conceptual framework. A basic understanding of factors potentially important to successful implementation can help to guide clinicians who accept the challenge of implementing tobacco use treatment in surgical care.