Background: HPV infection is implicated in approximately half of global penile squamous cell carcinoma (PSCC) cases. Previous studies on HPV DNA and p16INK4a status in PSCC have yielded inconclusive prognostic findings. This meta-analysis aims to elucidate the prognostic role of HPV in PSCC by pooling data on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Methods: We systematically searched Medline and Embase up to January 2023 for relevant human studies. Data from eligible publications reporting HPV DNA or p16INK4a status, along with and DFS, DSS, or OS outcomes, were extracted. A random-effects meta-analysis model was used to synthesize data, with study weights based on size and significance. The study protocol was registered with PROSPERO (CRD42019131355). Results: Out of 544 studies screened, 34 publications were included, comprising a pooled sample size of 3,944 patients. p16INK4a-positive status was associated with improved OS (hazard ratio [HR], 0.54; 95% CI, 0.39-0.75; I 2=31%), DFS (HR, 0.52; 95% CI, 0.29-0.94; I 2=20%), and DSS (HR, 0.34; 95% CI, 0.23-0.50; I 2=18%). HPV DNA positivity was significantly associated with improved DFS (HR, 0.63; 95% CI, 0.46-0.87; I 2=13%) and DSS (HR, 0.46; 95% CI, 0.29-0.75; I 2=47%) but not OS (HR, 0.92; 95% CI, 0.74-1.11; I 2=0%). Conclusions: This meta-analysis, comprising the largest number of patients with PSCC to date, shows a notable correlation between p16INK4a immunohistochemistry positivity and survival outcomes. These findings support the understanding that penile cancer cases not associated with HPV tend to behave more aggressively. We support p16INK4a immunohistochemistry testing as part of the initial diagnostic evaluation of patients with PSCC.

Summary: Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9–25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6–15), RCC (11.86, range: 6–15), UC (11.50, range: 9–14), and PC (10.56, range: 6–15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

PURPOSE Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy. METHODS The primary end points were acceptability and feasibility. Acceptability was defined as the proportion of patients approached who consented to participate, setting a benchmark of at least 50% for this metric. Feasibility was gauged by the completion rate of the intervention among the participants; it required at least 50% of participants to fully complete the intervention and at least 70% to finish half of the administered questionnaires. The secondary end points included knowledge assessment and patient-reported outcomes (PROs). PROs were evaluated using validated instruments. To discern the changes between pre- and post-educational module quiz scores, we used the Wilcoxon signed-rank test. Time-course data of PROs were visualized using line plots and then compared using paired t-tests. RESULTS From November 2022 to July 2023, 20 of 22 (90%) patients approached for the study consented and enrolled. Of the enrolled patients, 60% completed all questionnaires and knowledge assessments at every time point and 75% completed at least half of the surveys and questionnaires. Significant pre/post differences were noted in two of six quizzes in the knowledge assessment. This study population did not experience a significant change in PRO scores after starting therapy. CONCLUSION The mHealth application designed for education and symptom management in patients with advanced RCC undergoing combination ICI-TKI has proven to be both acceptable and feasible, meeting previous research benchmarks.

413 Background: Renal Cell Carcinoma (RCC) is a global public health burden with over 400,000 new cases and over 175,000 deaths annually. Immune checkpoint inhibitors (ICI) in combination with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) has become an integral part of the management of patients with advanced RCC which requires adaptation of healthcare systems to provide information and optimize the management of drug-related adverse events. This study aims to improve the education on therapy-related symptoms and the quality of life of patients with RCC treated with these drugs. Methods: We created a smartphone application (mHealth) that combines educational data, patient-reported outcomes, and peer-to-peer interactions. We aim to assess the feasibility of expansion of this pilot study. We prospectively enrolled stage IV RCC patients (n=20) undergoing treatment with combination ICI and VEGF-TKI. Therapy-related symptom education, knowledge PRO questionnaires, and peer-to-peer support were provided at baseline and at different time points throughout this study duration (Table 1). Time-course data of PROs were visualized using line plots and then compared with paired t-tests. The study's primary endpoint was to assess acceptability and feasibility of mHealth, defined as acceptable if 50% of patients offered participation agree to be enrolled and feasible if 50% of enrolled patients complete the intervention with 70% of these completing at least 50% of survey instruments. Results: Eighty percent of patients were male, 80% were white, 75% had at least some college education, 70% were married, and the mean age of the cohort was 66 years.A total of 22 patients were approached for the study with an acceptance rate of 90%. Sixty percent of patients completed every questionnaire and knowledge assessment at every timepoint of the intervention and 75% of those completed at least 50% of instruments. PROs data showed no significant difference compared to baseline in global health status, functional scales, and symptom scales across the 24 weeks. We noticed an improvement in the patients' knowledge assessment on symptom management after completion of the mHealth knowledge component. Conclusions: Our pilot study was considered acceptable and feasible, showing preliminary evidence of improvement in patient knowledge with mHealth. Our future direction will be to assess, in a larger randomized study, the efficacy of mHealth in improving the quality of life of patients with advanced RCC treated with ICI and VEGF-TKI. Clinical trial information: NCT05579847 . [Table: see text]

INTRODUCTION:Immune checkpoint blockade (ICB) is a rapidly emerging field of oncology that has revolutionized the metastatic renal cell carcinoma (mRCC) treatment. Four recent treatment regimens Nivolumab-Ipilimumab, Pembrolizumab-Axitinib, Nivolumab-Cabozantinib, and Pembrolizumab-Lenvatinib-have demonstrated improved clinical endpoints compared to standard of care and are endorsed by NCCN (2021). However, data on patient-reported outcomes (PROs) for patients receiving these regimens are limited. We conducted a comparative assessment of the quality and standardization of PROs endpoints and data reported for these randomized controlled trials (RCTs).PATIENTS AND METHODS:We systematically identified all RCTs evaluating combination ICB for ccRCC. PROs-specific data were abstracted from the final version of 4 RCT protocols, as well as clinical and PROs specific manuscripts published between April 2018 and April 2021. We used 3 previously published guides standardizing PROs research to objectively score the data: (i) 24-point PROEAS; (ii) 12-point SPIRIT-PRO; and (iii) 14-point CONSORT-PRO.RESULTS:The CheckMate 214, KEYNOTE 426, CheckMate 9ER, and CLEAR studies had PROEAS scores of 88% (21/24), 37% (9/24), 83% (20/24), and 16% (4/24), respectively, and SPIRIT-PRO scores of 50% (6/12), 75% (9/12), 66% (8/12), and 41% (5/12) respectively. The CONSORT-PRO scores were 86% (12/14) for CheckMate 214 and 43% (6/14) for CheckMate 9ER, but scores were not available for the CLEAR and KEYNOTE 426 studies because of a lack of sufficient data. The average SPIRIT-PRO score across the 4 RCTs was 58%, indicating a reasonable adoption of PROs research in data management and analysis. The CheckMate 214 trial had the longest follow-up and most comprehensive published PROs data.CONCLUSION:Our analysis identified the limitations of current PROs data in combination ICB approved for mRCC. This analysis will enable clinicians to better interpret the current PROs results and emphasize the importance of better incorporation of PROs endpoints in future mRCC trial design.

BACKGROUNDPatient-reported outcomes (PROs) promote patient-centeredness in clinical trials; however, in the field of the rapidly emerging and clinically impressive immunotherapy, data on PROs are limited.METHODSWe systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale: the PRO Endpoints Analysis Score (PROEAS) based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium.RESULTSWe assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (IQR= 9-29). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data including 13 (56.5%) that published a secondary dedicated manuscript. Half of these 14 trials scored < 13 points on the 24-point PROEAS. The mean score was 12.71 (range= 5-17; SD = 3.71), and none met all the recommendations of the SISAQOL Consortium.CONCLUSIONSuboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of this data in cancer immunotherapy development and approval.

105 Background: Patient-reported outcomes (PROs) are a primary tool to evaluate the effect of a given drug on the health-related quality of life from a patient’s perspective and to maximize the value of patient-centeredness in drug development and approval. In this study, we aimed to evaluate the current trend in reporting, analysis and interpretation of PRO data. Methods: We conducted a systematic review of the FDA archives, identifying all cancer immunotherapy drug approvals between the years 2011 and 2019. We then retrieved the clinical trials that respectively led to these drug approvals from PubMed and ClinicalTrials.gov. We systematically screened for PROs and assessed their analytic tools and interpretation methods that were collected from the published journal articles and their study protocols. If one FDA approval was supported by more than one clinical trial, we included all studies in our review. An FDA approval was considered to include PROs if they were reported in at least one of the supporting trials. Results: Thirty-seven clinical trials leading to 35 immunotherapy drug approvals were identified. More than half (54%) did not publish any PROs. While PROs were reported in the primary clinical outcomes manuscript of 4 trials (11%) and in a secondary separately published paper for 13 trials (35%). The median time between the primary and secondary papers was 22 months (range: 5 - 40). In the 17 published PROs, the hypothesis was broad in 12 (71%), not reported in 4 (24%) and specific in only 1 (6%). Ten (59%) were reported as exploratory endpoints, five (29%) as secondary endpoints, and two (12%) did not specify the PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (71%) and QLQ-C30 (65%). Control for type I error was needed but not done in 15 (88%). Fourteen (82%) described an approach for dealing with missing PRO assessments. None reported on significant differences based on race and ethnicity of participants. Conclusions: Suboptimal reporting and delays in publication of PROs occur regularly in cancer immunotherapy trials. Increased efforts are needed to enhance standardization and quality reporting of PROs to maximize the value of this data in cancer immunotherapy drug approval.

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.

The Texas Medicaid 1115 Transformation Waiver reforms the state's safety net systems by creating a Delivery System Reform Incentive Payment incentive pool for innovative healthcare delivery. The Waiver supports the design and implementation of transformative projects. As part of the Waiver requirements, regions created Learning Collaboratives to collaborate on project implementation and outcomes. This paper describes the experience of one region in adapting the Institute for Healthcare Improvement Breakthrough Series (IHI BTS) model, as a framework for their Learning Collaborative. Implementation of the Learning Collaborative was systematic, multidimensional, and regularly evaluated. Some features of the IHI model were adapted, specifically longer Plan-Do-Check-Act cycles and the lack of a single clinical focus. This experience demonstrates the ability of a region to improve health from a more diverse perspective than the traditional IHI BTS Collaboratives. Within the region, organizations are connecting, agencies are building continuums of care, and stakeholders are involved in healthcare delivery. The initial stages show a remarkable increase in communication and enhanced relationships between providers. At the end of the 5-year Waiver, evaluation of the impact of the regional and cohort Learning Collaboratives will determine how well the adapted IHI BTS model facilitated improvements in the community's health.

Importance Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals. Objective We aimed to clarify this association and evaluate type-specific β-HPV involvement. Data Sources We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: "human papillomavirus" and "cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms." Study Selection Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific β-HPV. Data Extraction and Synthesis We first assessed the heterogeneity among study-specific ORs using the Q statistic and I2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot-based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. Main Outcomes and Measures Pooled ORs and 95% CIs for overall β-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. Results Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between β-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development. Conclusions and Relevance This study serves as added evidence supporting β-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts.

OBJECTIVES:This study evaluates the prevalence of diabetes mellitus (DM) among patients with arterial hypertension, and indirectly, the crucial impact of adopting screening for diabetes as a standard procedure for all patients diagnosed with arterial hypertension.MATERIALS & METHODS:This cross-sectional study was performed on a sample of hypertensive patients recruited from three different university hospitals in Lebanon. Blood pressure and glycemic blood measurements were determined in all subjects. In addition, a complete clinical history and physical exam were performed. Data was entered and analyzed using SPSS 19.0. Frequencies for the different variables were calculated, and the chi-square and independent sample t-tests were conducted.RESULTS:This study included 294 patients. Prevalence of diabetes was 27%, and 23% of diabetic patients were newly diagnosed. More than half of the subjects suffering from DM had uncontrolled blood pressure, contrasted with only one third of the non-diabetic subjects with uncontrolled hypertension.CONCLUSION:The prevalence of DM in patients with essential hypertension was more than double that of the general population. Therefore, major recommendations would be to adopt strictly the diabetes screening requirements and aggressive management among hypertensive patients to minimize both the health and cost burdens associated with undetected DM.

BACKGROUND The US health care system is characterized by high health expenditures with penultimate outcomes. This ecological study evaluates the associations between wealth, health expenditure, and cancer outcomes at the state level. METHODS We extracted gross domestic product (GDP) and health expenditure per capita from the 2009 Bureau of Economic Analysis and the Centers for Medicare & Medicaid Services, respectively. Using data from the NCI, we retrieved colorectal cancer (CRC), breast cancer, and all-cancer age-adjusted rates and computed mortality/incidence (M/I) ratios. We used the Spearman's rank correlation to determine the association between the financial indicators and cancer outcomes, and we constructed geographic distribution maps to describe these associations. RESULTS GDP per capita significantly correlated with lower M/I ratios for all cancers, breast cancer, and CRC. As for health expenditure per capita, preliminary analysis highlighted a rift between the Northeastern and Southern states, which translated into worse breast and all-cancer outcomes in Southern states. Further analysis showed that higher health expenditure significantly correlated with decreased breast cancer M/I ratio. However, CRC outcomes were not significantly affected by health expenditure, nor were all-cancer outcomes. CONCLUSIONS All cancers, breast cancer, and CRC outcomes significantly correlated with wealth, whereas only breast cancer correlated with higher health expenditure. Future research is needed to evaluate the potential role of policies in optimizing resource allocation in the states' efforts against CRC and minimizing disparities in interstate cancer outcomes.

BACKGROUND:Preventing Ventilator-associated events (VAE) is a major challenge. Strictly monitoring for ventilator-associated pneumonia (VAP) is not sufficient to ensure positive outcomes. Therefore, the surveillance definition was updated and a change to the broader VAE was advocated. OBJECTIVE:This paper summarizes the scientific efforts assessing VAP preventive bundles and the recent transition in surveillance methods. METHODS:We conducted a systematic review to identify lessons from past clinical studies assessing VAP prevention bundles. We then performed a thorough literature review on the recent VAE surveillance algorithm, highlighting its advantages and limitations. CONCLUSION:VAP prevention bundles have historically proven their efficacy and the introduction of the new VAE definition aimed at refining and objectivizing surveillance methods. Randomized controlled trials remain vital to determine the effect of VAE prevention on patient outcomes. We recommend expanding beyond limited VAP prevention strategies towards VAE prevention bundles.

BACKGROUND:Strategic planning has been presented as a valuable management tool. However, evidence of its deployment in healthcare and its effect on organizational performance is limited in low-income and middle-income countries (LMICs). The study aimed to explore the use of strategic planning processes in Lebanese hospitals and to investigate its association with financial performance.METHODS:The study comprised 79 hospitals and assessed occupancy rate (OR) and revenue-per-bed (RPB) as performance measures. The strategic planning process included six domains: having a plan, plan development, plan implementation, responsibility of planning activities, governing board involvement, and physicians' involvement.RESULTS:Approximately 90% of hospitals have strategic plans that are moderately developed (mean score of 4.9 on a 1-7 scale) and implemented (score of 4.8). In 46% of the hospitals, the CEO has the responsibility for the plan. The level of governing board involvement in the process is moderate to high (score of 5.1), whereas physician involvement is lower (score of 4.1). The OR and RPB amounted to respectively 70% and 59 304 among hospitals with a strategic plan as compared with 62% and 33 564 for those lacking such a plan. No statistical association between having a strategic plan and either of the two measures was detected. However, the findings revealed that among hospitals that had a strategic plan, higher implementation levels were associated with lower OR (p < 0.05).CONCLUSIONS:In an LMIC healthcare environment characterized by resource limitation, complexity, and political and economic volatility, flexibility rather than rigid plans allow organizations to better cope with environmental turbulence.