Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1, MYC, and AR Nuclear Import.

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.

Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

Rapid Response to the Legalization of Fentanyl Test Strips in Alabama: An Academic-Community Partnership.

In June 2022, Alabama legalized fentanyl test strips (FTS). In response to this new opportunity to prevent overdoses, Project Linkage, Education, and Prevention (LEAP)-an academic-community partnership providing substance use prevention services-quickly purchased FTS and started distributing them in the Birmingham area. We describe how the Addiction Prevention Coalition, a substance use education and harm reduction provider, distributed 7300 FTS in the first year of legalization via Project LEAP and discuss its efforts to decrease substance use among young people. (Am J Public Health. 2024;114(8):785-788. https://doi.org/10.2105/AJPH.2024.307681).

Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.

Association of Pharmacist Interventions With Adverse Drug Events and Potential Adverse Drug Events.

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs). METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs. RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33. CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.

Incidence and Geographical Distribution of Adrenocortical Carcinoma: Retrospective Analysis of a State Cancer Registry.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC "hot spots" that could be linked to environmental exposures. METHODS: A retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer. RESULTS: We identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case. CONCLUSION: Our analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.

Coping among Black college women: A transformative study of gendered racism.

Black women in the United States are placed at higher risk for mental health challenges, including distress and depression, due to structural inequities. Black college women enrolled in predominantly White institutions may be particularly exposed to stressors related to gendered racism, but there is limited knowledge about this population's coping strategies. A cross-sectional survey and focus group were utilized to understand and disrupt participants' experiences of gendered racism. In phase one, a survey assessing coping strategies and mental health outcomes was conducted with 168 Black women enrolled at a predominantly White institution in the southeastern United States. Logistic regression results indicated that several coping strategies including behavioral disengagement, self-blame, self-distraction, denial, and positive reframing were significantly associated with depression and psychological distress, all p < 0.05. Phase two included a single focus group with a subset of the sample from phase one. The focus group findings supplemented the survey results, suggesting education (more accurately consciousness-raising) as a foundational theme that seemed to create space for humor and social support as coping subthemes and created a transformative space where participants spoke openly about gendered racism. Findings from this study highlight the societal underpinnings that shape Black college women's experiences of gendered racism. College settings should endeavor to provide formal and informal support for Black women to minimize the harms related to gendered racism.

Impact of an HIV pre-exposure prophylaxis dashboard on veteran PrEP enrollment.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective at reducing the risk of human immunodeficiency virus (HIV) acquisition in at-risk individuals; however, it is largely underutilized. The Veterans Health Administration has created an HIV PrEP dashboard to identify at-risk veterans in attempt to increase PrEP enrollment. OBJECTIVE: This study aimed to determine whether the use of an HIV PrEP dashboard would prove effective at increasing PrEP enrollment at a single facility. METHODS: This was a single-center quality improvement project. Three pharmacists used the HIV PrEP dashboard and retrospective chart review to identify eligible patients for PrEP. A multimodal process of contacting patients was conducted. The primary objective was to evaluate the number of patients who enrolled in PrEP during the study period. Secondary objectives included evaluating the ability of the HIV PrEP dashboard to identify eligible patients, identify effective strategies to target PrEP enrollment, and compare those patients who accepted with those who declined PrEP to evaluate barriers to enrollment. RESULTS: Of the 94 patients reviewed, 26 patients (27.7%) were found eligible for PrEP. Of the eligible patients, 3 patients (11.5%) were enrolled, and 7 patients (26.9%) declined PrEP. The others were lost to follow-up (9 of 26, 34.6%), had no action taken on a chart note to provider (6 of 26, 23.1%), or did not have a primary care provider assigned at the local facility (1 of 26, 3.9%). The 3 patients who were successfully enrolled in PrEP were all contacted and prescribed PrEP through the infectious diseases (ID) clinic. There were no statistically significant differences between the cohorts of patients who accepted and declined PrEP. CONCLUSIONS: The use of an HIV PrEP dashboard aided in identifying eligible patients for PrEP. Enrollment through the ID clinic was the most successful modality. Further research is needed to characterize barriers to PrEP uptake and to develop strategies to increase prescribing from non-ID providers.

Case Report: Cefepime Induced Neurotoxicity Following a Change in Infusion Time.

Purpose: Cefepime is an antibiotic associated with cefepime induced neurotoxicity (CIN), particularly in those with reduced renal function, or in cases of inappropriate medication dosing. This report describes a case of CIN associated with a change in infusion duration from 180 to30 minutes, which to the best of our knowledge has not been previously reported in the literature. Summary: A 73-year old male was treated with extended infusion cefepime over 180 minutes while hospitalized with recurrent pneumonia. On discharge, cefepime was continued as outpatient parenteral antimicrobial therapy (OPAT) administered over 30 minutes. The patient began to experience symptoms of neurotoxicity after 1 day of receiving OPAT, which subsequently led to a readmission as neurological symptoms worsened. Cefepime was discontinued and symptoms resolved within 48 hours. Renal function was stable throughout treatment and no other causes for neurotoxicity were noted. Conclusion: This is a unique case of CIN secondary to shortened infusion time, which is clinically relevant, particularly during transitions of care. Further investigation, including more widespread use of therapeutic drug monitoring will be beneficial to further elucidate the relationship between infusion time and CIN development.

Phase I Single Ascending Dose and Food Effect Study in Healthy Adults and Phase I/IIa Multiple Ascending Dose Study in Patients with Pulmonary Tuberculosis to Assess Pharmacokinetics, Bactericidal Activity, Tolerability, and Safety of OPC-167832.

OPC-167832, an inhibitor of decaprenylphosphoryl-ß-d-ribose 2'-oxidase, demonstrated potent antituberculosis activity and a favorable safety profile in preclinical studies. This report describes the first two clinical studies of OPC-167832: (i) a phase I single ascending dose (SAD) and food effects study in healthy participants; and (ii) a 14-day phase I/IIa multiple ascending dose (MAD; 3/10/30/90 mg QD) and early bactericidal activity (EBA) trial in participants with drug-susceptible pulmonary tuberculosis (TB). OPC-167832 was well tolerated at single ascending doses (10 to 480 mg) in healthy participants and multiple ascending doses (3 to 90 mg) in participants with TB. In both populations, nearly all treatment-related adverse events were mild and self-limiting, with headache and pruritus being the most common events. Abnormal electrocardiograms results were rare and clinically insignificant. In the MAD study, OPC-167832 plasma exposure increased in a less than dose-proportional manner, with mean accumulation ratios ranging from 1.26 to 1.56 for Cmax and 1.55 to 2.01 for area under the concentration-time curve from 0 to 24 h (AUC0-24h). Mean terminal half-lives ranged from 15.1 to 23.6 h. Pharmacokinetics (PK) characteristics were comparable to healthy participants. In the food effects study, PK exposure increased by less than ~2-fold under fed conditions compared to the fasted state; minimal differences were observed between standard and high-fat meals. Once-daily OPC-167832 showed 14-day bactericidal activity from 3 mg (log10 CFU mean ± standard deviation change from baseline; -1.69 ± 1.15) to 90 mg (-2.08 ± 0.75), while the EBA of Rifafour e-275 was -2.79 ± 0.96. OPC-167832 demonstrated favorable pharmacokinetic and safety profiles, as well as potent EBA in participants with drug-susceptible pulmonary TB.

Trends and Projections in National United States Health Care Spending for Gastrointestinal Malignancies (1996-2030).

BACKGROUND & AIMS: The management of gastrointestinal (GI) cancers is associated with high health care spending. We estimated trends in United States (US) health care spending for patients with GI cancers between 1996 and 2016 and developed projections to 2030. METHODS: We used economic data, adjusted for inflation, developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-adjusted prevalence of GI cancers was estimated from the Global Burden of Diseases Study. Prevalence-adjusted temporal trends in the US health care spending in patients with GI cancers, stratified by cancer site, age, and setting of care, were estimated using joinpoint regression, expressed as annual percentage change (APC) with 95% confidence intervals (CIs). Autoregressive integrated moving average models were used to project spending to 2030. RESULTS: In 2016, total spending for GI cancers was primarily attributable to colorectal ($10.50 billion; 95% CI, $9.35-$11.70 billion) and pancreatic cancer ($2.55 billion; 95% CI, $2.23-$2.82 billion), and primarily for inpatient care (64.5%). Despite increased total spending, more recent per-patient spending for pancreatic (APC 2008-2016, -1.4%; 95% CI, -2.2% to -0.7%), gallbladder/biliary tract (APC 2010-2016, -4.3%; 95% CI, -4.8% to -3.8%), and gastric cancer (APC 2011-2016, -4.4%; 95% CI, -5.8% to -2.9%) decreased. Increasing price and intensity of care provision was the largest driver of higher expenditures. By 2030, it is projected more than $21 billion annually will be spent on GI cancer management. CONCLUSIONS: Total spending for GI cancers in the US is substantial and projected to increase. Expenditures are primarily driven by inpatient care for colorectal cancer, although per-capita spending trends differ by GI cancer type.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Racial disparities in new-onset diabetes mellitus in prostate cancer patients on androgen deprivation therapy: a retrospective analysis of TriNetX data.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in the US and androgen deprivation therapy (ADT) is the most frequently used systemic therapy for PCa. Data suggest that ADT is associated with an increased risk of new-onset diabetes mellitus (NODM) and cardiovascular complications. As the incidence and mortality of PCa are highest among the African American (AA) population, it is important to evaluate the difference in the incidence of NODM and ischemic heart disease (IHD) between AA men compared to Caucasian men. METHODS: This is a retrospective cohort study utilizing the TriNetX database to assess NODM and IHD risk, risk difference, and risk ratio (RR) after recent ADT initiation in an AA cohort and a Caucasian cohort of patients with PCa. Propensity score matching (PSM) was performed by age, BMI, and confounding comorbidities. RESULTS: After matching, the cohort included 1159 AA patients and 843 Caucasian patients with NODM after ADT initiation. The IHD cohort included 1269 AA patients and 1248 Caucasian patients. The risk of incidence of NODM is higher among AA men at 11.6% risk compared to Caucasian men at 7.4%. The risk difference is 4.1% (95% CI = 3.4, 4.9) p = 0.000. The RR is 1.56 (95% CI = 1.43, 1.70). In contrast, risk difference and risk ratio of IHD was not significant between AA and Caucasian groups. CONCLUSION: ADT exposure increases the risk of NODM in men with PCa, especially among AA men compared with Caucasian men. Men receiving ADT should be monitored routinely for signs and symptoms of metabolic syndrome and diabetes. Targeted close monitoring of AA men on ADT would be critical to prevent and treat metabolic complications with potential of reducing disparities in PCa morbidity.

External validation of a novel electronic risk score for cancer-associated thrombosis in a comprehensive cancer center.

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 [95% CI 0.69-0.72] with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 [95% CI 0.62-0.65]. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.

Patient and Clinician Sociodemographics and Sexual History Screening at a Multisite Federally Qualified Health Center: A Mixed Methods Study.

PURPOSE: In 2018, there were 68 million sexually transmitted infections in the United States. Sexual history screening is an evidence-based practice endorsed by guidelines to identify risk of these infections and adverse sexual health outcomes. In this mixed methods study, we investigated patient- and clinician-level characteristics associated with receipt of sexual history screening, and contextualized these differences in more depth. METHODS: We collected sociodemographics of patients from the electronic health record and sociodemographics of their primary care clinicians via a census survey. Semistructured interviews were conducted with key practice staff. We conducted multilevel crossed random effects logistic regression analysis and thematic analysis on quantitative and qualitative data, respectively. RESULTS: A total of 53,246 patients and 56 clinicians from 13 clinical sites participated. Less than one-half (42.4%) of the patients had any sexual history screening documented in their health record. Patients had significantly higher odds of documented screening if they were gay or lesbian (OR = 1.23), were cisgender women (OR = 1.10), or had clinicians who were cisgender women (OR = 1.80). Conversely, patients' odds of documented screening fell significantly with age (OR per year = 0.99) and with the number of patients their clinicians had on their panels (OR per patient = 0.99), and their odds were significantly lower if their primary language was not English (OR = 0.91). In interviews, key staff expressed discomfort discussing sexual health and noted assumptions about patients who are older, in long-term relationships, or from other cultures. Discordance of patient-clinician gender and patients' sexual orientation were also noted as barriers. CONCLUSIONS: Interventions are needed to address the interplay between the social and contextual factors identified in this study, especially those that elicited discomfort, and the implementation of sexual history screening.

Identifying socioeconomic and biophysical factors driving forest loss in protected areas.

Protected areas (PAs) are a commonly used strategy to confront forest conversion and biodiversity loss. Although determining drivers of forest loss is central to conservation success, understanding of them is limited by conventional modeling assumptions. We used random forest regression to evaluate potential drivers of deforestation in PAs in Mexico, while accounting for nonlinear relationships and higher order interactions underlying deforestation processes. Socioeconomic drivers (e.g., road density, human population density) and underlying biophysical conditions (e.g., precipitation, distance to water, elevation, slope) were stronger predictors of forest loss than PA characteristics, such as age, type, and management effectiveness. Within PA characteristics, variables reflecting collaborative and equitable management and PA size were the strongest predictors of forest loss, albeit with less explanatory power than socioeconomic and biophysical variables. In contrast to previously used methods, which typically have been based on the assumption of linear relationships, we found that the associations between most predictors and forest loss are nonlinear. Our results can inform decisions on the allocation of PA resources by strengthening management in PAs with the highest risk of deforestation and help preemptively protect key biodiversity areas that may be vulnerable to deforestation in the future.

Identificación de los factores biofísicos y socioeconómicos que impulsan la pérdida de bosques en las áreas protegidas Resumen Las áreas protegidas son una estrategia de uso común para hacer frente a la conversión forestal y la pérdida de biodiversidad. Aunque determinar los factores que impulsan la pérdida de bosques es fundamental para el éxito de la conservación, su comprensión se ve limitada por los supuestos de modelación convencionales. Utilizamos la regresión de bosques aleatorios para evaluar los posibles impulsores de la deforestación en las áreas protegidas de México, considerando las relaciones no lineales y las interacciones de orden superior que subyacen a los procesos de deforestación. Los impulsores socioeconómicos (densidad de carreteras, densidad de población humana) y las condiciones biofísicas subyacentes (precipitaciones, distancia al agua, elevación, pendiente) fueron predictores más fuertes de la pérdida de bosques que las características de las áreas protegidas, como la edad, el tipo y la efectividad de la gestión. Dentro de las características de las áreas protegidas, las variables que reflejan una gestión colaborativa y equitativa y el tamaño del área protegida fueron los predictores más potentes de la pérdida de bosques, aunque con menor poder explicativo que las variables socioeconómicas y biofísicas. A diferencia de los métodos utilizados anteriormente, que suelen basarse en el supuesto de relaciones lineales, observamos que las asociaciones entre la mayoría de los predictores y la pérdida de bosques no son lineales. Nuestros resultados pueden servir de base para la toma de decisiones sobre la asignación de los recursos para las áreas protegidas, reforzando la gestión en las zonas protegidas con mayor riesgo de deforestación y ayudando a proteger de forma preventiva zonas clave para la biodiversidad que pueden ser vulnerables a la deforestación en el futuro.

Six-month intervention with wild blueberries improved speed of processing in mild cognitive decline: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: As the sector of the population over 65y increases, cognitive decline and dementia become a public health issue. Interventions to improve brain health and thus, quality of life for older adults are needed. OBJECTIVE: It was hypothesized that those consuming a flavonoid-rich, lyophilized wild blueberry powder would evidence improvements in cognitive performance as measured behaviorally and electrophysiologically compared to those consuming a placebo powder across a 6-month intervention period. DESIGN: In a double-blind, randomized placebo-controlled trial, participants experiencing cognitive issues as determined by scores on the Montreal Cognitive Assessment (MoCA) were randomized to consume either wild blueberry (n = 44) or placebo (n = 42) powder daily for 6 months. Participants who were not experiencing any cognitive issues were included as a reference group (n = 45). Participants were tested at baseline and outcome on the Cambridge Neurological Test Automated Battery (CANTAB) and in an electrophysiological paradigm known as event-related potentials (ERP). RESULTS: Tests of specific cognitive abilities using the CANTAB showed speed of processing not only improved in the blueberry intervention group relative to the placebo group across the 6-month intervention, but blueberries also restored speed of processing to the level of the reference group. The ERP results also showed that, relative to those consuming placebo, speed of processing improved for those in the blueberry group; this improvement was most prominent in those 75-80y. CONCLUSIONS: Consumption of wild blueberries for six months improves cognitive aging sequelae by improving the speed of information processing in older adults.Trial registration: ClinicalTrials.gov identifier: NCT01515098.

Systematic analysis of levels of evidence supporting American Academy of Ophthalmology Preferred Practice Pattern guidelines, 2012-2021.

BACKGROUND: Despite the increased emphasis on evidence-based medicine, the current state of evidence behind ophthalmology clinical practice guidelines is unknown. The purpose of this systematic analysis was to understand the levels of evidence (LOE) supporting American Academy of Ophthalmology (AAO) Preferred Practice Pattern (PPP) guidelines, assess changes over time, and compare LOE across ophthalmology subspecialties. METHODS: All current PPP guidelines and their immediate predecessors were comprehensively reviewed to identify all recommendations with LOE provided (I [randomized controlled trials], II [case-control or cohort studies], and III [nonanalytic studies]). RESULTS: Twenty-three out of 24 current PPPs had a prior edition. Among the PPPs with a prior edition, the number of recommendations with LOE decreased from 1254 in prior PPPs to 94 in current PPPs. The number of recommendations with LOE I decreased from 114 to 83, LOE II decreased from 147 to 2, and LOE III decreased from 993 to 9. However, the proportion of LOE I recommendations increased from 9 to 88%, driven by a disproportionate decrease in reporting of evidence lower than LOE I. Subgroup analysis by subspecialty showed similar trends (LOE I recommendations in prior PPPs vs current PPPs: retina: 57 [12%] vs 19 [100%]; cornea: 33 [5%] vs 24 [100%]; glaucoma: 9 [23%] vs 17 [100%]; cataract: 13 [17%] vs 18 [100%]). CONCLUSIONS: Trends in LOE reporting in PPP guidelines indicate an increasing emphasis on evidence from randomized controlled trials from 2012 to 2021. The decline in the number of recommendations with LOE reported suggests an area for improvement in future guidelines as the presence of LOE is crucial to facilitate interpretation of clinical practice guidelines.

Enhancing bladder cancer care through the multidisciplinary clinic approach.

INTRODUCTION: To report the impact of our 25-year multidisciplinary care delivery model experience on patients with muscle invasive bladder cancer treated at our National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center at Jefferson University. To our knowledge, our multidisciplinary genitourinary cancer clinic (MDC) is the longest continuously operating center of its kind at an NCI Cancer Center in the United States. MATERIALS AND METHODS: We selected a recent group of patients with cT2-4 N0-1 M0 bladder cancer seen in the Sidney Kimmel Cancer Center Genitourinary Oncology MDC from January 2016 to September 2019. These patients were identified retrospectively. SEER-18 (Surveillance, Epidemiology, and End Results) database, November 2019 submission was queried to obtain patients with similarly staged disease diagnosed between 2015 and 2017. Completion rates of radical cystectomy, use of neoadjuvant therapies, and survival outcomes were compared between the two cohorts. RESULTS: Ninety-one patients from the MDC form this time period were identified; 65.9% underwent radical cystectomy and 71.8% received neoadjuvant therapy in the form of chemotherapy, immune checkpoint inhibition or a combination of the two - higher than reported national trends for neoadjuvant therapies. Progression of disease was seen in 24.2% of patients. A total of 8675 patients met inclusion criteria in the SEER database. Rates of radical cystectomy were significantly higher in MCD patients when compared to SEER derived data (65.9% vs. 37.7%, p =< 0.001). MCD patients had significantly better cancer-specific survival (mean 20.4 vs. 18.3 months p = 0.028, median survival not reached). CONCLUSION: Our long term experience caring for patients with genitourinary malignancies such as bladder cancer in a uniform multidisciplinary team results in a high utilization of neoadjuvant therapies. When compared to a contemporary SEER-derived cohort, multidisciplinary patients were more likely to undergo radical cystectomy and had longer cancer-specific survival.

How Medication Adherence Affects Disease Management in Veterans with Glaucoma: Lessons Learned from a Clinical Trial.

INTRODUCTION: We conducted a secondary, real-world clinical assessment of a randomized controlled trial to determine how a glaucoma medication adherence intervention impacted the clinical outcomes of participants at 12 months post-randomization. Participants included veterans at a VA eye clinic with medically treated glaucoma who reported poor adherence and their companions, if applicable. METHODS: The treatment group received a glaucoma education session with drop administration instruction and virtual reminders from a "smart bottle" (AdhereTech) for their eye drops. The control group received a general eye health class and the smart bottle with the reminder function turned off. Medical chart extraction determined if participants in each group experienced visual field progression, additional glaucoma medications, or a recommendation for surgery or laser due to inadequate intraocular pressure control over the 12 months following randomization. The main outcome measure was disease progression, defined as visual field progression or escalation of glaucoma therapy, in the 12 months following randomization. RESULTS: Thirty-six versus 32% of the intervention (n = 100) versus control (n = 100) groups, respectively, experienced disease intensification. There was no difference between the intervention and control groups in terms of intensification (intervention vs. control group odds ratio: 1.20; 95% confidence interval: [0.67, 2.15]), including when age, race, and disease severity were accounted for in the logistic regression model. Those whose study dates included time during the COVID-19 pandemic were evenly distributed between groups. CONCLUSIONS: A multifaceted intervention that improved medication adherence for glaucoma for 6 months did not affect the clinical outcomes measured at 12 months post-randomization. Twelve months may not be long enough to see the clinical effect of this intervention or more than 6 months of intervention are needed.