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1.
Front Oncol ; 14: 1362244, 2024.
Article in English | MEDLINE | ID: mdl-39109281

ABSTRACT

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

2.
Am J Public Health ; 114(S6): S515-S524, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39083729

ABSTRACT

Objectives. To identify nationwide census tract‒level areas where improving colorectal cancer (CRC) screening uptake via targeted local preventive intervention may benefit Hispanic or Latino/a (H/L) groups defined by region or country of origin. Methods. Using 2021 Centers for Disease Control and Prevention PLACES and American Community Survey data, we applied geographically weighted regression and Getis-Ord Gi* hot spot procedures to identify CRC screening priority zones for H/L groups in the United States. Priority zones can be conceptualized as census tracts with strong inverse associations between percentage of a particular H/L group in the population and CRC screening rate, after adjusting for socioeconomic deprivation and lack of insurance. Results. We identified 6519, 3477, 3522, 1069, and 1424 census tract CRC screening priority zones for H/L communities of Mexican, Puerto Rican, Central/South American, Dominican, and Cuban heritage, respectively. Priority zones for H/L groups had strong spatial heterogeneity, and overlap of geographic patterns among H/L groups varied by region. Conclusions. Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefitting specific H/L communities in the United States. (Am J Public Health. 2024;114(S6):S515-S524. https://doi.org/10.2105/AJPH.2024.307733) [Formula: see text].


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Hispanic or Latino , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/ethnology , Hispanic or Latino/statistics & numerical data , United States , Early Detection of Cancer/statistics & numerical data , Female , Male , Middle Aged , Aged , Socioeconomic Factors , Mass Screening/statistics & numerical data
3.
Article in English | MEDLINE | ID: mdl-39082868

ABSTRACT

The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α-melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.

4.
Nat Microbiol ; 9(7): 1686-1699, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38898217

ABSTRACT

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.


Subject(s)
Antifungal Agents , Mutagenesis , Animals , Mice , Humans , Virulence/genetics , Antifungal Agents/pharmacology , China , Body Temperature , Disease Models, Animal , Ascomycota/genetics , Ascomycota/pathogenicity , Ascomycota/drug effects , Caspofungin/pharmacology , Microbial Sensitivity Tests , Fluconazole/pharmacology , Mycoses/microbiology , Drug Resistance, Multiple, Fungal/genetics , Drug Resistance, Fungal/genetics
5.
IJID Reg ; 11: 100368, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38742235

ABSTRACT

Background: Resistant Salmonella infections are a major global public health challenge particularly for multidrug-resistant (MDR) isolates manifesting as bloodstream infections (BSIs). Objectives: To evaluate clinical, phenotypic, and genotypic characteristics of extended-spectrum beta-lactamase (ESBL) producing Salmonella enterica BSIs from Qatar. Methods: Phenotypic ESBL Salmonella enterica from adult patients presenting with positive BSIs were collected between January 2019 to May 2020. Microbiological identification and characterization were performed using standard methods while genetic characteristics were examined through whole genome sequencing studies. Results: Of 151 episodes of Salmonella enterica BSI, 15 (10%) phenotypic ESBL isolates were collected. Recent travel was recorded in most cases (80%) with recent exposure to antimicrobials (27%). High-level resistance to quinolines, aminoglycosides, and cephalosporins was recorded (80-100%) while meropenem, tigecycline and colistin demonstrated universal susceptibility. Genomic evaluation demonstrated dominance of serotype Salmonella Typhi sequence type 1 (93%) while antimicrobial resistance genes revealed dominance of aminoglycoside resistance (100%), qnrS1 quinolones resistance (80%), blaCTX-M-15 ESBLs (86.7%), and paucity of AmpC resistance genes (6.7%). Conclusions: Invasive MDR Salmonella enterica is mainly imported, connected to patients from high prevalent regions with recent travel and antimicrobial use caused by specific resistant clones. In suspected cases of multidrug resistance, carbapenem therapy is recommended.

6.
Vaccine ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802291

ABSTRACT

BACKGROUND: Our goal was to provide an overview of uptake rates across vaccine types and factors associated with vaccine uptake among cancer survivor populations. METHODS: A literature search was conducted using Ovid MEDLINE® ALL (Wolters Kluwer), Embase (Elsevier) and CINAHL Complete (EBSCO) databases and according to PRISMA guidelines. Eligible articles were limited to those examining vaccination uptake among cancer survivors who had completed treatment, reported factors associated with uptake (e.g., barriers and facilitators), and published in English between 2011 and 2021. Two independent reviewers screened citations for inclusion and two performed data abstraction, verified by an arbiter. RESULTS: The search returned 4,215 total articles, and 271 duplicates were removed. During abstract/title screening, 212 articles were identified. Following full-text screening, 47 articles/abstracts were found to meet inclusion criteria, 16 articles/abstracts were removed, and 31 studies were included in the review. Among the 31 studies, participant age ranged from 9 years to adults of all ages. Vaccine types included: influenza (n = 18), human papillomavirus (n = 10), pneumococcal (n = 8), hepatitis A/B (n = 1), shingles (n = 1), measles (n = 1), tetanus/diphtheria (n = 1), and haemophilus influenza B (n = 1). Vaccine uptake varied greatly across studies, vaccine types, and participant populations. Factors affecting vaccination uptake included sociodemographic variables and social determinants of health, health beliefs/attitudes/knowledge, provider recommendation, and cancer treatment/clinical variables. CONCLUSIONS: Our findings highlight the need for further examining factors associated with vaccine uptake, the need for clinical guidelines that specifically address vaccination among cancer survivors, and potential targets for multi-level interventions to improve vaccination rates among cancer survivor populations.

7.
Antibiotics (Basel) ; 13(4)2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38666996

ABSTRACT

Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.

9.
JAMA Ophthalmol ; 142(4): 319-320, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38451495
10.
J Cancer Surviv ; 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520598

ABSTRACT

PURPOSE: Adherence to oral endocrine therapy (ET) remains an issue for up to half of women prescribed these medications. There is emerging data that Black breast cancer survivors (BCS) have lower rates of ET adherence. Given the disparities in breast cancer recurrence and survival for Black BCS compared to their White counterparts, the goal of this study is to better understand barriers to ET adherence among Black BCS from the patient and provider perspectives. METHODS: In this qualitative study, we conducted semi-structured interviews between October 29, 2021, and March 1, 2023. Interviews were recorded and transcribed, and coded data were organized into primary and secondary themes. Participants were recruited from a single academic cancer center. A convenience sample of 24 Black BCS and 9 medical oncology providers was included. Eligible BCS were 18 years or older, English-speaking, diagnosed with stage I-III hormone receptor-positive breast cancer, who had initiated ET. RESULTS: Mean age of the BCS was 55 years (interquartile range, IQR 17 years). About one-fourth had a high school diploma or less (26.1%) and 47% completed a college education or higher. Approximately one-third of participants had annual household incomes of $40,000 or less (30.4%) or more than $100,000 (30.4%). Forty-three percent of the patient participants had private insurance; 11% were insured through Medicaid or the federal healthcare exchange; 26.1% had Medicare; and 13% were uninsured. Of the 9 medical oncology providers interviewed, 2 were advanced practice providers, and 7 were medical oncologists. We found 3 major themes: (1) Black BCS often had concerns about ET before initiation; (2) after initiation, both BCS and providers reported side effects as the most impactful barrier to ET adherence; and (3) survivors experienced challenges with managing ET side effects. CONCLUSIONS: Our results suggest that multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black women and may reduce disparities in outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black breast cancer survivors.

11.
Microb Genom ; 10(1)2024 Jan.
Article in English | MEDLINE | ID: mdl-38226964

ABSTRACT

Candida glabrata is a commensal yeast of the gastrointestinal tract and skin of humans. However, it causes opportunistic infections in immunocompromised patients, and is the second most common Candida pathogen causing bloodstream infections. Although there are many studies on the epidemiology of C. glabrata infections, the fine- and large-scale geographical nature of C. glabrata remain incompletely understood. Here we investigated both the fine- and large-scale population structure of C. glabrata through genome sequencing of 80 clinical isolates obtained from six tertiary hospitals in Qatar and by comparing with global collections. Our fine-scale analyses revealed high genetic diversity within the Qatari population of C. glabrata and identified signatures of recombination, inbreeding and clonal expansion within and between hospitals, including evidence for nosocomial transmission among coronavirus disease 2019 (COVID-19) patients. In addition to signatures of recombination at the population level, both MATa and MATα alleles were detected in most hospitals, indicating the potential for sexual reproduction in clinical environments. Comparisons with global samples showed that the Qatari C. glabrata population was very similar to those from other parts of the world, consistent with the significant role of recent anthropogenic activities in shaping its population structure. Genome-wide association studies identified both known and novel genomic variants associated with reduced susceptibilities to fluconazole, 5-flucytosine and echinocandins. Together, our genomic analyses revealed the diversity, transmission patterns and antifungal drug resistance mechanisms of C. glabrata in Qatar as well as the relationships between Qatari isolates and those from other parts of the world.


Subject(s)
Candida glabrata , Cross Infection , Humans , Candida glabrata/genetics , Cross Infection/epidemiology , Genome-Wide Association Study , Metagenomics , Genomics , Recombination, Genetic
12.
J Cancer Educ ; 39(1): 18-26, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37702848

ABSTRACT

The current study examined cancer prevention and early detection awareness (pre-workshop) and changes in knowledge (from pre- to post-workshop) among Hispanic/Latino (H/L) community members who participated in Spanish-language educational outreach events in Puerto Rico (PR) and Florida (FL). Spanish-language educational outreach events were comprised of an educational session lasting approximately 45-60 min and were delivered to groups in rural and urban community settings by a single trained community health educator (CHE). The research team assessed sociodemographic characteristics, personal and familial cancer health history, as well as awareness and knowledge (pre-test) of a range of cancer prevention and screening topics. Following the presentation, participants completed a post-test knowledge survey which also measured likelihood of engaging in cancer screening, cancer preventive behaviors, and cancer research as a result of information presented during the session. Change in the average knowledge score was evaluated using a paired samples t-test. Post-session likelihood of completing cancer screening and preventive behaviors and engaging in cancer research were examined using descriptive statistics and group/site comparisons. The percentage reporting awareness of screening procedures ranged from 33% (PSA test) to 79% (mammogram). H/L in PR reported higher percentage of stool blood test awareness when compared to H/L in FL (χ2(1)= 19.20, p<.001). The average knowledge score increased from 5.97 at pre-test to 7.09 at post-test (Cohen's d=0.69). The increase was significant across all participants (t(315)= 12.4, p<.001), as well as within the FL site (t(124)= 6.66, p<.001, d=0.59) and the PR site (t(190)=10.66, p<.001, d=0.77). Results from this study suggest that educational outreach events delivered to H/L community members by a CHE are valuable strategies to address challenges regarding cancer screening knowledge and engagement in multiple behaviors.


Subject(s)
Early Detection of Cancer , Health Knowledge, Attitudes, Practice , Neoplasms , Humans , Community-Institutional Relations , Florida , Hispanic or Latino , Neoplasms/diagnosis , Neoplasms/prevention & control , Prospective Studies , Puerto Rico
13.
Mol Ecol ; 33(3): e17228, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38037712

ABSTRACT

Soil and plant-associated protistan communities play a key role in shaping bacterial and fungal communities, primarily through their function as top-down predators. However, our understanding of how pathogen invasion influences these protistan communities and their relationships with bacterial and fungal communities remains limited. Here, we studied the protistan communities along the soil-plant continuum of healthy chilli peppers and those affected by Fusarium wilt disease (FWD), and integrated bacterial and fungal community data from our previous research. Our research showed that FWD was associated with a significant enrichment of phagotrophic protists in roots, and also increased the proportion and connectivity of these protists (especially Cercozoa and Ciliophora) in both intra- and inter-kingdom networks. Furthermore, the microbiome of diseased plants not only showed a higher relative abundance of functional genes related to bacterial anti-predator responses than healthy plants, but also contained a greater abundance of metagenome-assembled genomes with functional traits involved in this response. The increased microbial inter-kingdom associations between bacteria and protists, coupled with the notable bacterial anti-predator feedback in the microbiome of diseased plants, suggest that FWD may catalyse the associations between protists and their microbial prey. These findings highlight the potential role of predatory protists in influencing microbial assembly and functionality through top-down forces under pathogenic stress.


Subject(s)
Ciliophora , Microbiota , Mycobiome , Plants , Bacteria/genetics , Soil , Soil Microbiology
14.
J Behav Med ; 47(2): 295-307, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38127175

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) and liver cancer are two of the leading causes of cancer death in the United States and persistent disparities in CRC and liver cancer incidence and outcomes exist. Chronic hepatitis C virus (HCV) infection is one of the main contributors to liver cancer. Effective screening for both CRC and HCV exist and are recommended for individuals based upon age, regardless of gender or sex assigned at birth. Recommendations for both screening behaviors have been recently updated. However, screening rates for both CRC and HCV are suboptimal. Targeting adoption of multiple screening behaviors has the potential to reduce cancer mortality and disparities. OBJECTIVE: To examine psychosocial factors associated with completion of CRC and HCV screenings in order to inform a multi-behavioral educational intervention that pairs CRC and HCV screening information. METHODS: A cross-sectional survey was conducted with participants (N = 50) recruited at two community health centers in Florida (United States). Kruskal-Wallis and Fisher's exact tests were used to examine associations between completion of both CRC and HCV screening, CRC and HCV knowledge, Preventive Health Model constructs (e.g., salience and coherence, response efficacy, social influence), and sociodemographic variables. RESULTS: Most participants were White (84%), female (56%), insured (80%), and reported a household income of $25,000 or less (53%). 30% reported ever previously completing both CRC and HCV screenings. Prior completion of both screening behaviors was associated with higher educational attainment (p = .014), having health insurance (p = .022), being U.S.-born (p = .043), and higher salience and coherence scores for CRC (p = .040) and HCV (p = .004). CONCLUSIONS: Findings demonstrate limited uptake of both CRC and HCV screenings among adults born between 1945 and 1965. Uptake was associated with multiple sociodemographic factors and health beliefs related to salience and coherence. Salience and coherence are modifiable factors associated with completion of both screening tests, suggesting the importance of incorporating these health beliefs in a multi-behavioral cancer education intervention. Additionally, health providers could simultaneously recommend and order CRC and HCV screening to improve uptake among this age cohort.


Subject(s)
Colorectal Neoplasms , Hepatitis C, Chronic , Liver Neoplasms , Adult , Infant, Newborn , Humans , United States , Female , Cross-Sectional Studies , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/psychology , Hepacivirus , Early Detection of Cancer/psychology , Mass Screening , Community Health Centers
15.
Cancer ; 130(9): 1684-1692, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38150285

ABSTRACT

BACKGROUND: This study examined repeat colorectal cancer screening rates at 12 and 24 months as part of a randomized intervention trial among Black persons living in the United States and factors associated with screening adherence. METHODS: Participants completed a survey assessing demographics and Preventive Health Model (PHM) factors (e.g., self efficacy, susceptibility) and received either a culturally targeted photonovella plus free fecal immunochemical test (FIT) kits (intervention group) or a standard educational brochure plus free FIT kits (comparison group). FIT return was assessed at 6, 12, and 24 months. Descriptive statistics summarized patterns of repeat screening. Logistic regression models assessed FIT uptake overtime, and demographic and PHM factors associated with screening adherence. RESULTS: Participants (N = 330) were U.S.-born (93%), non-Hispanic (97%), and male (52%). Initial FIT uptake within 6 months of enrollment was 86.6%, and subsequently dropped to 54.5% at 12 months and 36.6% at 24 months. Higher FIT return rates were observed for the brochure group at 24 months (51.5% vs 33.3% photonovella, p = .023). Multiple patterns of FIT kit return were observed: 37% completed FIT at all three time points (full adherence), 22% completed two of three (partial adherence), 29% completed one of three (partial adherence), and 12% did not return any FIT kits (complete nonadherence). Predictors of full adherence were higher levels of education and self-efficacy. CONCLUSIONS: Full adherence to repeat screening was suboptimal. Most participants had partial adherence (one or two of three) to annual FIT screening. Future studies should focus on strategies to support repeat FIT screening.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , Male , Colorectal Neoplasms/diagnosis , Mass Screening , Occult Blood , United States/epidemiology , Patient Compliance , Black or African American , Female
18.
JAMA Oncol ; 9(11): 1565-1573, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37768670

ABSTRACT

Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC. Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS). Design, Setting, and Participants: This multicenter, phase 2, double-blind, placebo-controlled randomized clinical trial enrolled 142 patients with stage III to IV carcinoma of the oropharynx (p16 negative), larynx, and hypopharynx with a Zubrod performance status of 0 to 1 who met predefined blood chemistry criteria from October 18, 2012, to April 18, 2017 (median follow-up, 4.1 years). Data analysis was performed from December 1, 2020, to December 4, 2020. Intervention: Patients were randomized (1:1) to 70 Gy (6 weeks) plus 2 cycles of cisplatin (every 3 weeks) plus either 1500 mg per day of lapatinib (CRT plus lapatinib) or placebo (CRT plus placebo). Main Outcomes and Measures: The primary end point was PFS, with 69 events required. Progression-free survival rates between arms for all randomized patients were compared by 1-sided log-rank test. Secondary end points included OS. Results: Of the 142 patients enrolled, 127 (median [IQR] age, 58 [53-63] years; 98 [77.2%] male) were randomized; 63 to CRT plus lapatinib and 64 to CRT plus placebo. Final analysis did not suggest improvement in PFS (hazard ratio, 0.91; 95% CI, 0.56-1.46; P = .34) or OS (hazard ratio, 1.06; 95% CI, 0.61-1.86; P = .58) with the addition of lapatinib. There were no significant differences in grade 3 to 4 acute adverse event rates (83.3% [95% CI, 73.9%-92.8%] with CRT plus lapatinib vs 79.7% [95% CI, 69.4%-89.9%] with CRT plus placebo; P = .64) or late adverse event rates (44.4% [95% CI, 30.2%-57.8%] with CRT plus lapatinib vs 40.8% [95% CI, 27.1%-54.6%] with CRT plus placebo; P = .84). Conclusion and Relevance: In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of CRT. Although the results of this trial indicate that accrual to a non-HPV HNC-specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01711658.


Subject(s)
Carcinoma , Head and Neck Neoplasms , Humans , Male , Female , Cisplatin/adverse effects , Lapatinib , Head and Neck Neoplasms/drug therapy , Carcinoma/drug therapy , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/adverse effects
19.
Transl Vis Sci Technol ; 12(9): 1, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37656449

ABSTRACT

Purpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.


Subject(s)
Geographic Atrophy , Wet Macular Degeneration , Humans , Child, Preschool , Ranibizumab/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Prospective Studies , Vascular Endothelial Growth Factor A , Visual Acuity , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapy , Retina/diagnostic imaging
20.
Patient Educ Couns ; 115: 107888, 2023 10.
Article in English | MEDLINE | ID: mdl-37463555

ABSTRACT

BACKGROUND: Advancing health equity requires innovative patient education approaches for adapting English-language evidence-based interventions (EBIs) to resonate with multicultural, multilingual audiences. OBJECTIVE: Examine the benefit, functionality, and practical considerations of transcreation (translation + cultural adaptation) as a critical and salient learner-centric process for developing a Spanish-language intervention (photonovella + video): Un examen sencillo para un colon saludable (A simple test for a healthy colon). PATIENT/COMMUNITY INVOLVEMENT: We involved patients/community members in a participatory reflective process, from problem identification to intervention design, development, delivery, and impact measurement. METHODS: A community-based participatory research (CBPR) approach involving formative research plus systematic iterative pretesting and learner verification checks augmented by a community advisory board guided the transcreation processes. RESULTS: Data collected using a learner-centric approach effectively produced a new Spanish-language EBI and substantiated the value of co-learner/co-design methods. Learner-centric methods identified cultural nuances that were treated as knowledge and integrated into the intervention materials and study design. Pilot testing of the intervention among Latinos receiving care at community clinics demonstrated improved initial colorectal cancer screening uptake, awareness, and perceived susceptibility. DISCUSSION: Inherent in the transcreation process was learner involvement that informed essential modification and adaptation of the materials. The transcreation methods led to the development of a culturally salient intervention that maintained theoretical integrity and message intent as well as behavioral activation. Findings have broad implications for the creation and transfer of EBIs to new audiences for greater adoption, engagement, and 'reach' of interventions. PRACTICAL VALUE: Transcreation aligns with a growing paradigm shift in health communication science that brings to light the beneficial effect that construction and application of cultural knowledge has on patient education toward health equity.


Subject(s)
Colorectal Neoplasms , Community-Based Participatory Research , Language , Patient Participation , Humans , Hispanic or Latino , Research Design , Culturally Competent Care , Social Determinants of Health , Health Equity
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