Smoking Behaviors Among Indigenous Pregnant People Compared to a Matched Regional Cohort.

INTRODUCTION: Smoking commercial tobacco products is highly prevalent in American Indian and Alaska Native (Indigenous) pregnancies. This disparity directly contributes to maternal and fetal mortality. Our objective was to describe cigarette smoking prevalence, cessation intervention uptake, and cessation behaviors of pregnant Indigenous people compared to sex and age-matched regional cohort. AIMS AND METHODS: Pregnancies from an Indigenous cohort in Olmsted County, Minnesota, identified in the Rochester Epidemiology Project, were compared to pregnancies identified in a sex and age-matched non-Indigenous cohort from 2006 to 2019. Smoking status was defined as current, former, or never. All pregnancies were reviewed to identify cessation interventions and cessation events. The primary outcome was smoking prevalence during pregnancy, with secondary outcomes measuring uptake of smoking cessation interventions and cessation. RESULTS: The Indigenous cohort included 57 people with 81 pregnancies, compared to 226 non-Indigenous people with 358 pregnancies. Smoking was identified during 45.7% of Indigenous pregnancies versus 11.2% of non-Indigenous pregnancies (RR: 3.25, 95% CI = 1.98-5.31, p ≤ .0001). Although there was no difference in uptake of cessation interventions between cohorts, smoking cessation was significantly less likely during Indigenous pregnancies compared to non-Indigenous pregnancies (OR: 0.23, 95% CI = 0.07-0.72, p = .012). CONCLUSIONS: Indigenous pregnant people in Olmsted County, Minnesota were more than three times as likely to smoke cigarettes during pregnancy compared to the non-indigenous cohort. Despite equivalent uptake of cessation interventions, Indigenous people were less likely to quit than non-Indigenous people. Understanding why conventional smoking cessation interventions were ineffective at promoting cessation during pregnancy among Indigenous women warrants further study. IMPLICATIONS: Indigenous pregnant people in Olmsted County, Minnesota, were greater than three times more likely to smoke during pregnancy compared to a regional age matched non-Indigenous cohort. Although Indigenous and non-Indigenous pregnant people had equivalent uptake of cessation interventions offered during pregnancy, Indigenous people were significantly less likely to quit smoking before fetal delivery. This disparity in the effectiveness of standard of care interventions highlights the need for further study to understand barriers to cessation in pregnant Indigenous people.

Incidence, risk factors, and outcome of Clostridioides difficile infection following urological surgeries.

PURPOSE: To assess the incidence, risk factors, and clinical outcomes associated with (Clostridioides difficile infection) CDI following urological surgery, which is the leading cause of nosocomial diarrhea and a growing public health burden. METHODS: We queried the National Surgical Quality Improvement Program (NSQIP) to identify patients undergoing urological surgery in 2015-2016. We evaluated the 30-day incidence and factors associated with postoperative CDI and 30-day hospital readmission and length of stay as secondary outcomes. Among the subset of patients undergoing radical cystectomy with urinary diversion (surgery with highest CDI incidence) we used multivariable logistic regression analysis to evaluate independent clinical and demographic factors associated with postoperative CDI. RESULTS: We identified 98,463 patients during the study period. The overall 30-day incidence of CDI was 0.31%, but varied considerably across surgery type. The risk of CDI was greatest following radical cystectomy with urinary diversion (2.72%) compared to all other urologic procedures (0.19%) and was associated with increased risk of hospital readmission (p < 0.0001), re-operation (p < 0.0001), and longer mean length of stay (p < 0.0001) in this cohort. Among patients undergoing radical cystectomy with urinary diversion, multivariable logistic regression revealed that preoperative renal failure (OR: 5.30, 95% CI 1.13-24.9, p = 0.035) and blood loss requiring transfusion (OR: 1.67, 95% CI 1.15-2.44, p = 0.0075) were independently associated with CDI. CONCLUSIONS: In a nationally representative cohort, the incidence of CDI was low but varied substantially across surgery types. CDI was most common following radical cystectomy and associated with potentially modifiable factors such as blood transfusion and significantly longer length of stay.

Evaluating resilience as a predictor of outcomes in lung transplant candidates.

BACKGROUND: Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). METHODS: Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. RESULTS: Participation was 55.3% (N = 199). Baseline RISC-10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing > 1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P = .01). CONCLUSION: One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.

TEN-YEAR FOLLOW-UP OF PATIENTS WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS.

PURPOSE: To identify the visual acuity outcomes of patients with age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections over a 10-year period. METHODS: This was a retrospective, cohort study of eyes with exudative age-related macular degeneration that received ≥2 intravitreal anti-vascular endothelial growth factor injections and had at least 10 years of follow-up after the initiation of treatment. Snellen visual acuity was recorded at baseline and then annually until the last year of follow-up. Optical coherence tomography data were collected at the time of treatment initiation and at the last examination visit. A subanalysis was performed on patients who continued to receive anti-vascular endothelial growth factor therapy using a modified treat and extend protocol versus those who discontinued treatment for longer than 1 year. RESULTS: One hundred thirty eyes of 115 patients met the inclusion criteria. The mean follow-up after treatment initiation was 11.1 ± 0.7 years. Eyes received an average of 45.1 ± 32.3 intravitreal injections in total and a mean of 5 to 7 injections per year. The baseline mean logMAR visual acuity was 0.61 ± 0.5 (Snellen acuity 20/81), and the final mean logMAR visual acuity was 0.88 ± 0.7 (20/152, P value = <0.0001). There were 40 eyes that received at least one injection every year. These eyes did not have a significant change in visual acuity between the baseline and final examinations 0.47 ± 0.4 (20/59 vs. 0.58 ± 0.5 [20/76, P = 0.28]), whereas the eyes that did not receive at least one injection every year saw a significant decline in visual acuity 0.67 ± 0.5 (20/94 vs. 1.01 ± 0.7 [20/205, P < 0.0001]). CONCLUSION: Eyes with exudative age-related macular degeneration that received intravitreal injections every year had stable visual acuity over a 10-year period. Continuous intravitreal anti-vascular endothelial growth factor therapy may stabilize visual acuity for 10 years and potentially longer.

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BACKGROUND: Temozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 µM). METHODS: MGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 µM. Clonogenic GSC surviving 500 µM TMZ (GSC-500 µM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC. RESULTS: The molecular signatures characterized an activation of protective stress responses in GSC-500 µM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 µM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 µM TMZ and GSC-parental to 35 µM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489). CONCLUSIONS: These data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT.

Long-Term Visual Outcomes in Exudative Age-Related Macular Degeneration Patients With Unanticipated Gaps in Therapy.

BACKGROUND AND OBJECTIVES: This study's objective was to describe long-term visual outcomes of patients with age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor injections who were lost to follow-up and then resumed treatment with anti-vascular endothelial growth factor injections. MATERIALS AND METHODS: This was a retrospective cohort study of eyes with at least 7 years of follow-up following the initiation of treatment for wet AMD with and without gaps in therapy. RESULTS: The baseline mean logMAR visual acuity was 0.65 ± 0.5 (Snellen acuity 20/89) in eyes with gaps in therapy and 0.53 ± 0.3 (20/68) in eyes without gaps. In the initial 7-year follow-up period, the eyes with gaps in therapy had significantly worse visual acuity (P < .001) and this remained significant when accounting for baseline visual acuity (P < .001). CONCLUSIONS: Gaps in intravitreal injection therapy for exudative AMD were negatively associated with visual acuity. Adherence to therapy is important to address in the care of patients with exudative AMD. [Ophthalmic Surg Lasers Imaging Retina 2022;53:481-489.].

Indigenous Smoking Behaviors in Olmsted County, Minnesota: A Longitudinal Population-Based Study.

OBJECTIVE: To describe smoking behaviors and pharmaceutical cessation aid uptake in a population-based Indigenous cohort compared with an age- and sex-matched non-Indigenous cohort. PATIENTS AND METHODS: Using the health record-linkage system of the Rochester Epidemiology Project (January 1, 2006, to December 31, 2019), smoking data of Indigenous residents of Olmsted County in Minnesota were abstracted to define the smoking prevalence, incidence, cessation, relapse after cessation, and pharmaceutical smoking cessation aid uptake compared with a matched non-Indigenous cohort. Prevalence was analyzed with a modified Poisson regression; cessation and relapse were evaluated with generalized estimating equations. Incidence was evaluated with a Cox proportional hazards model. RESULTS: Smoking prevalence was higher in the Indigenous cohort (39.0% to 47.0%; n=898) than the matched cohort (25.6% to 30.3%; n=1780). Pharmaceutical uptake was higher among the Indigenous cohort (35.8% of n=584 ever smokers vs 16.3% of n=778 ever smokers; P<.001). Smoking cessation events occurred more frequently in the Indigenous cohort (relative risk, 1.10; 95% CI, 1.06 to 1.13; P<.001). Indigenous former smokers were more likely to resume smoking (relative risk, 3.03; 95% CI, 2.93 to 3.14; P<.001) compared with the matched cohort. These findings were independent of socioeconomic status, age, and sex. CONCLUSION: Smoking in this Indigenous cohort was more prevalent compared with a sex- and age-matched non-Indigenous cohort despite more smoking cessation events and higher use of smoking cessation aids in the Indigenous cohort. The relapse rate after achieving cessation in the Indigenous cohort was more than three times higher than the non-Indigenous cohort. This finding has not been previously described and represents a potential target for relapse prevention efforts in US Indigenous populations.

Long-Term Follow-up of Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To determine the long-term visual outcomes and intravitreal injection burden of patients with exudative age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with exudative AMD treated with intravitreal anti-VEGF injections with annual office visits for at least 7 years. METHODS: Snellen visual acuity was measured at baseline and then annually until the last year of follow-up. The number of injections was recorded on an annual basis during each year of follow-up. MAIN OUTCOME MEASURES: The change in the frequency of injections over time along with the change in visual acuity each year from the baseline visit through 7 years. RESULTS: During this period, 533 eyes of 429 patients were treated for exudative AMD. Of these, 391 eyes (73%) met the inclusion criteria of annual office visits and received a mean of 5.8 ± 2.5 intravitreal injections per year. The baseline mean visual acuity was 0.6 ± 0.5 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/80), and the 7-year visual acuity was 0.8 ± 0.6 logMAR (Snellen equivalent, 20/126; P < 0.0001). When compared with the 142 eyes that did not undergo an office visit for a continuous 12-month period, eyes with annual office visits showed similar baseline mean visual acuity (0.7 logMAR vs. 0.6 logMAR; P = 0.2102), but more injections per year (P < 0.0001). Of the 533 total eyes, 124 eyes (23%) maintained better than 20/40 visual acuity at 7 years. These eyes received more injections overall per year (6.5 vs. 5.5 injections per year; P = 0.0007). CONCLUSIONS: In a real-world setting, eyes that maintained consistent, long-term follow-up received significantly more intravitreal injections per year than eyes with inconsistent follow-up. Eyes with 20/40 or better vision at study conclusion received more injections per year than eyes with worse than 20/40 vision.