Development and Implementation of a Hospitalist Faculty Development Program in a University- and Community-Based Multihospital System.

OBJECTIVES: Robust faculty development (FD) is an emerging area of focus within hospital medicine, a relatively new specialty with limited mentorship infrastructure to find and develop a professional niche. There are few descriptions in the literature of establishing and evaluating an FD program with strategies to evaluate success, invite collaboration, and achieve feasible, useful metrics. METHODS: We created our University Division of Hospital Medicine's FD Program to help community and academic hospitalist faculty fulfill professional goals in (and beyond) quality improvement, leadership, education, and clinical skills. We describe program development, initial implementation, and early evaluation results. We outline program roles and offerings such as professional development awards, lectures, and mentorship structures. RESULTS: Our program was successfully implemented, measured by engagement and participation via preliminary indicators suggesting programmatic effectiveness: faculty who applied for (and continued participation in) mentorship and faculty development awards and faculty who attended our lecture series. Since program implementation, faculty retention has increased, and percentages of faculty reporting they were likely to remain were stable, even during the coronavirus disease 2019 pandemic. Scholarly production increased and the number of division associate professors/professors grew from 2 in 2015 to 19 in 2024. CONCLUSIONS: Our experience can guide institutions seeking to support and encourage faculty professional development. Lessons learned include the importance of needs assessment and leadership commitment to meeting identified needs; how a steering committee can amplify the effectiveness and relevance of FD efforts; and the utility of multiple recognition strategies-quarterly newsletters, monthly clinical recognition, mentions on social media-to support and encourage faculty.

An Epidemic Supplanted by a Pandemic: Vaping-Related Illness and COVID-19.

Before the coronavirus disease 2019 (COVID-19) pandemic, vaping-related illness was the prevailing public health concern. The incidence of vaping-related illnesses-mainly e-cigarette, or vaping, product use-associated lung injury (EVALI)-went from a peak in September 2019 to a low in February 2020, and the Centers for Disease Control and Prevention decided to discontinue the collection of EVALI case reports. Despite the decrease in EVALI with the arrival of COVID-19, EVALI should still be considered a differential diagnosis for people with COVID-19 for reasons outlined in this review. This narrative review describes vaping devices, summarizes the adverse health effects of vaping on the lungs and other systems, considers the potential interplay between vaping and COVID-19, and highlights gaps in knowledge about vaping that warrant further research.

Evaluation of a Multifaceted Protocol in Reducing Unnecessary Telemetry Monitoring across a Large Healthcare System.

OBJECTIVES: Telemetry is frequently overused in hospitals. The goal of this study was to evaluate a telemetry protocol aimed at decreasing inappropriate telemetry utilization across four different hospitals within a large healthcare system by modifying the electronic telemetry order to incorporate the 2017 American Heart Association practice guidelines on the appropriate use of telemetry and using an electronic nursing screening task form to safely discontinue telemetry. METHODS: We performed a retrospective analysis of telemetry utilization before and after we implemented a protocol across four hospitals within a large healthcare system. We compared the average number of days of telemetry monitoring and hospital length of stay during the preintervention period with the 6-month postintervention period. RESULTS: There were a total of 23,774 encounters evaluated. There was a statistically and clinically significant 24% decrease in telemetry duration between pre- and postintervention time periods (P < 0.0001). The mean (standard error) telemetry duration was 4.11 (0.17) and 2.36 (0.13) days in pre- and postintervention periods, respectively. CONCLUSIONS: The results of our study demonstrate a statistically significant decrease in overall duration of telemetry monitoring by nearly 1.75 days across each of the four hospitals with the implementation of a multifaceted telemetry protocol that included hardwiring the American Heart Association practice guidelines into the electronic order and using a nursing-driven discontinuation protocol.

Corporate political activity in the context of unhealthy food advertising restrictions across Transport for London: A qualitative case study.

BACKGROUND: Diets with high proportions of foods high in fat, sugar, and/or salt (HFSS) contribute to malnutrition and rising rates of childhood obesity, with effects throughout the life course. Given compelling evidence on the detrimental impact HFSS advertising has on children's diets, the World Health Organization unequivocally supports the adoption of restrictions on HFSS marketing and advertising. In February 2019, the Greater London Authority introduced novel restrictions on HFSS advertising across Transport for London (TfL), one of the most valuable out-of-home advertising estates. In this study, we examined whether and how commercial actors attempted to influence the development of these advertising restrictions. METHODS AND FINDINGS: Using requests under the Freedom of Information Act, we obtained industry responses to the London Food Strategy consultation, correspondence between officials and key industry actors, and information on meetings. We used an existing model of corporate political activity, the Policy Dystopia Model, to systematically analyse arguments and activities used to counter the policy. The majority of food and advertising industry consultation respondents opposed the proposed advertising restrictions, many promoting voluntary approaches instead. Industry actors who supported the policy were predominantly smaller businesses. To oppose the policy, industry respondents deployed a range of strategies. They exaggerated potential costs and underplayed potential benefits of the policy, for instance, warning of negative economic consequences and questioning the evidence underlying the proposal. Despite challenging the evidence for the policy, they offered little evidence in support of their own claims. Commercial actors had significant access to the policy process and officials through the consultation and numerous meetings, yet attempted to increase access, for example, in applying to join the London Child Obesity Taskforce and inviting its members to events. They also employed coalition management, engaging directly and through business associations to amplify their arguments. Some advertising industry actors also raised the potential of legal challenges. The key limitation of this study is that our data focused on industry-policymaker interactions; thus, our findings are unable to present a comprehensive picture of political activity. CONCLUSIONS: In this study, we identified substantial opposition from food and advertising industry actors to the TfL advertising restrictions. We mapped arguments and activities used to oppose the policy, which might help other public authorities anticipate industry efforts to prevent similar restrictions in HFSS advertising. Given the potential consequences of commercial influence in these kinds of policy spaces, public bodies should consider how they engage with industry actors.

Management of Refractory Breathlessness: a Review for General Internists.

Internists frequently care for patients who suffer from breathlessness in both the inpatient and the outpatient settings. Patients may experience chronic refractory breathlessness despite thorough evaluation and management of their underlying medical illnesses. Left unmanaged, chronic breathlessness is associated with worsened quality of life, more frequent visits to the emergency room, and decreased activity levels, as well as increased levels of depression and anxiety. This narrative review summarizes recent research on interventions for the relief of breathlessness, including both non-pharmacologic and pharmacologic options.

How food companies use social media to influence policy debates: a framework of Australian ultra-processed food industry Twitter data.

OBJECTIVE: To understand if, and how, Australian ultra-processed food industry actors use Twitter to influence food and health policy debates and produce a conceptual framework to describe such influence. DESIGN: Twitter data of prominent industry actors were defined through purposive sampling and inductively coded to investigate possible influence on food and health policy debates. These are described using descriptive statistics and coded extracts. SETTING: Australia. PARTICIPANTS: Twitter accounts of nine prominent ultra-processed food industry actors, including major trade associations. RESULTS: Ultra-processed food industry actors actively used Twitter to influence food and health policy debates. Seven overarching strategies were identified: co-opting public health narratives; opposing regulation; supporting voluntary, co- or self-regulation; engaging policy processes and decision-makers; linking regulatory environments to the need for ongoing profitability; affecting public perceptions and value judgements; and using ignorance claims to distort policy narratives. Each lobbying strategy is underpinned with tactics described throughout and captured in a framework. CONCLUSIONS: The current study creates a framework to monitor how food industry actors can use social media to influence food and health policy debates. As such, social media appears to be not only an important commercial determinant of health for brand marketing, but also an extension of lobbying practices to reshape public perceptions of corporate conduct and policy-making.

Linguistic Analysis of Online Communication About a Novel Persecutory Belief System (Gangstalking): Mixed Methods Study.

BACKGROUND: Gangstalking is a novel persecutory belief system whereby those affected believe they are being followed, stalked, and harassed by a large number of people, often numbering in the thousands. The harassment is experienced as an accretion of innumerable individually benign acts such as people clearing their throat, muttering under their breath, or giving dirty looks as they pass on the street. Individuals affected by this belief system congregate in online fora to seek support, share experiences, and interact with other like-minded individuals. Such people identify themselves as targeted individuals. OBJECTIVE: The objective of the study was to characterize the linguistic and rhetorical practices used by contributors to the gangstalking forum to construct, develop, and contest the gangstalking belief system. METHODS: This mixed methods study employed corpus linguistics, which involves using computational techniques to examine recurring linguistic patterns in large, digitized bodies of authentic language data. Discourse analysis is an approach to text analysis which focuses on the ways in which linguistic choices made by text creators contribute to particular functions and representations. We assembled a 225,000-word corpus of postings on a gangstalking support forum. We analyzed these data using keyword analysis, collocation analysis, and manual examination of concordances to identify discursive and rhetorical practices among self-identified targeted individuals. RESULTS: The gangstalking forum served as a site of discursive contest between 2 opposing worldviews. One is that gangstalking is a widespread, insidious, and centrally coordinated system of persecution employing community members, figures of authority, and state actors. This was the dominant discourse in the study corpus. The opposing view is a medicalized discourse supporting gangstalking as a form of mental disorder. Contributors used linguistic practices such as presupposition, nominalization, and the use of specialized jargon to construct gangstalking as real and external to the individual affected. Although contributors generally rejected the notion that they were affected by mental disorder, in some instances, they did label others in the forum as impacted/affected by mental illness if their accounts if their accounts were deemed to be too extreme or bizarre. Those affected demonstrated a concern with accumulating evidence to prove their position to incredulous others. CONCLUSIONS: The study found that contributors to the study corpus accomplished a number of tasks. They used linguistic practices to co-construct an internally coherent and systematized persecutory belief system. They advanced a position that gangstalking is real and contested the medicalizing discourse that gangstalking is a form of mental disorder. They supported one another by sharing similar experiences and providing encouragement and advice. Finally, they commiserated over the challenges of proving the existence of gangstalking.

Managing the tension: From innovation to application in health professions education.

Innovations in education are essential for solving problems and introducing new ways of thinking. However, implementation of these innovations must take several factors into consideration, including the context, the environment, the stakeholders, the technology needed, the cost, the pace of implementation, appropriateness, and available resources. When these factors are not balanced and considered, tensions arise. This paper describes tensions in five major educational domains, namely curriculum, instruction, assessment, accreditation/regulation, and faculty development. For each of these domains, the typical problems are described, and solutions are presented to manage the tension.

Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells.

One of the central challenges of transplantation is the development of alloreactivity despite the use of multiagent immunoprophylaxis. Effective control of this immune suppression-resistant T-cell activation represents one of the key unmet needs in the fields of both solid-organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly translational nonhuman primate (NHP) model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylaxed transplant recipients. Our results demonstrate the complex character of the alloreactivity that develops during ongoing immunoprophylaxis and identify 3 key transcriptional hallmarks of breakthrough acute GVHD that are not observed in hyperacute GVHD: (1) T-cell persistence rather than proliferation, (2) evidence for highly inflammatory transcriptional programming, and (3) skewing toward a T helper (Th)/T cytotoxic (Tc)17 transcriptional program. Importantly, the gene coexpression profiles from human HCT recipients who developed GVHD while on immunosuppressive prophylactic agents recapitulated the patterns observed in NHP, and demonstrated an evolution toward a more inflammatory signature as time posttransplant progressed. These results strongly implicate the evolution of both inflammatory and interleukin 17-based immune pathogenesis in GVHD, and provide the first map of this evolving process in primates in the setting of clinically relevant immunomodulation. This map represents a novel transcriptomic resource for further systems-based efforts to study the breakthrough alloresponse that occurs posttransplant despite immunoprophylaxis and to develop evidence-based strategies for effective treatment of this disease.

Modelling the implications of reducing smoking prevalence: the public health and economic benefits of achieving a 'tobacco-free' UK.

INTRODUCTION: Smoking is still the most preventable cause of cancer, and a leading cause of premature mortality and health inequalities in the UK. This study modelled the health and economic impacts of achieving a 'tobacco-free' ambition (TFA) where, by 2035, less than 5% of the population smoke tobacco across all socioeconomic groups. METHODS: A non-linear multivariate regression model was fitted to cross-sectional smoking data to create projections to 2035. These projections were used to predict the future incidence and costs of 17 smoking-related diseases using a microsimulation approach. The health and economic impacts of achieving a TFA were evaluated against a predicted baseline scenario, where current smoking trends continue. RESULTS: If trends continue, the prevalence of smoking in the UK was projected to be 10% by 2035-well above a TFA. If this ambition were achieved by 2035, it could mean 97 300 +/- 5 300 new cases of smoking-related diseases are avoided by 2035 (tobacco-related cancers: 35 900+/- 4 100; chronic obstructive pulmonary disease: 29 000 +/- 2 700; stroke: 24 900 +/- 2 700; coronary heart disease: 7600 +/- 2 700), including around 12 350 diseases avoided in 2035 alone. The consequence of this health improvement is predicted to avoid £67 +/- 8 million in direct National Health Service and social care costs, and £548 million in non-health costs, in 2035 alone. CONCLUSION: These findings strengthen the case to set bold targets on long-term declines in smoking prevalence to achieve a tobacco 'endgame'. Results demonstrate the health and economic benefits that meeting a TFA can achieve over just 20 years. Effective ambitions and policy interventions are needed to reduce the disease and economic burden of smoking.

Modelling the implications of reducing smoking prevalence: the benefits of increasing the UK tobacco duty escalator to public health and economic outcomes.

INTRODUCTION: Taxing tobacco is one of the most effective ways to reduce smoking prevalence, mitigate its devastating consequential health harms and progress towards a tobacco-free society. This study modelled the health and economic impacts of increasing the existing cigarette tobacco duty escalator (TDE) in the UK from the current 2% above consumer price inflation to 5%. METHODS: A two-stage modelling process was used. First, a non-linear multivariate regression model was fitted to cross-sectional smoking data, creating longitudinal projections from 2015 to 2035. Second, these projections were used to predict the future incidence, prevalence and cost of 17 smoking-related diseases using a Monte Carlo microsimulation approach. A sustained increase in the duty escalator was evaluated against a baseline of continuing historical smoking trends and the existing duty escalator. RESULTS: A sustained increase in the TDE is projected to reduce adult smoking prevalence to 6% in 2035, from 10% in a baseline scenario. After increasing the TDE, only 65% of female and 60% of male would-be smokers would actually be smoking in 2035. The intervention is projected to avoid around 75 200 new cases of smoking-related diseases between 2015 and 2035. In 2035 alone, £49 m in National Health Service and social care costs and £192 m in societal premature mortality and morbidity costs are projected to be avoided. CONCLUSION: Increasing the UK TDE to 5% above inflation could effectively reduce smoking prevalence, prevent diseases and avoid healthcare costs. It would deliver substantial progress towards a tobacco-free society and should be implemented by the UK Government with urgency.

Management of Emotionally Challenging Responses of Hospitalized Patients with Cancer.

Cancer is the second leading cause of death in the United States, and the majority of hospital admissions of patients with cancer occur because of uncontrolled, urgent symptoms. In addition to complex physical presentations, these patients often manifest a number of complex emotional and psychological responses resulting in a unique set of healthcare needs and expectations. Inpatient generalists or hospitalists frequently serve as the primary providers of medical care for these patients. Formal training for nononcologists on effective communication strategies in managing patients with cancer in a hospital setting may not fully prepare generalists for challenging patient encounters, however. This review assists generalists in approaching emotionally charged encounters when caring for patients with cancer on the wards. We explore patient factors that negatively affect successful communication, some of which can be addressed through a multidisciplinary approach. In addition, we present a checklist of preventive strategies in addressing emotionally charged patient responses and offer a number of preventive and restorative management approaches for dealing with such encounters. We provide a practical framework for recognition and management of the psychosocial and emotional challenges in the care of hospitalized patients with cancer.

The Inclusion of Ethnic Minority Patients and the Role of Language in Telehealth Trials for Type 2 Diabetes: A Systematic Review.

BACKGROUND: Type 2 diabetes is a serious, pervasive metabolic condition that disproportionately affects ethnic minority patients. Telehealth interventions can facilitate type 2 diabetes monitoring and prevent secondary complications. However, trials designed to test the effectiveness of telehealth interventions may underrecruit or exclude ethnic minority patients, with language a potential barrier to recruitment. The underrepresentation of minorities in trials limits the external validity of the findings for this key patient demographic. OBJECTIVE: This systematic review examines (1) the research reporting practices and prevalence of ethnic minority patients included in telehealth randomized controlled trials (RCTs) targeting type 2 diabetes and the trial characteristics associated with recruiting a high proportion of minority patients, and (2) the proportion of included RCTs that report using English language proficiency as a patient screening criterion and how and why they do so. METHODS: Telehealth RCTs published in refereed journals targeting type 2 diabetes as a primary condition for adults in Western majority English-speaking countries were included. Ethnically targeted RCTs were excluded from the main review, but were included in a post hoc subgroup analysis. Abstract and full-text screening, risk of bias assessment, and data extraction were independently conducted by two reviewers. RESULTS: Of 3358 records identified in the search, 79 articles comprising 58 RCTs were included. Nearly two-thirds of the RCTs (38/58) reported on the ethnic composition of participants, with a median proportion of 23.5% patients (range 0%-97.7%). Fourteen studies (24%) that included at least 30% minority patients were all US-based, predominantly recruited from urban areas, and described the target population as underserved, financially deprived, or uninsured. Eight of these 14 studies (57%) offered intervention materials in a language other than English or employed bilingual staff. Half of all identified RCTs (29/58) included language proficiency as a participant-screening criterion. Language proficiency was operationalized using nonstandardized measures (eg, having sufficient "verbal fluency"), with only three studies providing reasons for excluding patients on language grounds. CONCLUSIONS: There was considerable variability across studies in the inclusion of ethnic minority patients in RCTs, with higher participation rates in countries with legislation to mandate their inclusion (eg, United States) than in those without such legislation (eg, United Kingdom). Less than 25% of the RCTs recruited a sizeable proportion of ethnic minorities, which raises concerns about external validity. The lack of objective measures or common procedures for assessing language proficiency across trials implies that language-related eligibility decisions are often based on trial recruiters' impressionistic judgments, which could be subject to bias. The variability and inconsistent reporting on ethnicity and other socioeconomic factors in descriptions of research participants could be more specifically emphasized in trial reporting guidelines to promote best practice. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews: CRD42015024899; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024899 (Archived by WebCite at http://www.webcitation.org/6kQmI2bdF).

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

BACKGROUND: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. RESULTS: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

Expectations in the field of the internet and health: an analysis of claims about social networking sites in clinical literature.

This article adopts a critical sociological perspective to examine the expectations surrounding the uses of social networking sites (SNSs) articulated in the domain of clinical literature. This emerging body of articles and commentaries responds to the recent significant growth in SNS use, and constitutes a venue in which the meanings of SNSs and their relation to health are negotiated. Our analysis indicates how clinical writing configures the role of SNSs in health care through a range of metaphorical constructions that frame SNSs as a tool, a conduit for information and a traversable space. The use of such metaphors serves not only to describe the new affordances offered by SNSs but also posits distinct lay and professional practices, while reviving a range of celebratory claims about the Internet and health critiqued in sociological literature. These metaphorical descriptions characterise SNS content as essentially controllable by autonomous users while reiterating existing arguments that e-health is both inherently empowering and risky. Our analysis calls for a close attention to these understandings of SNSs as they have the potential to shape future online initiatives, most notably by anticipating successful professional interventions while marginalising the factors that influence users' online and offline practices and contexts.

Radiotherapy and short-term androgen deprivation for localized prostate cancer.

BACKGROUND: It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. METHODS: From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. RESULTS: The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. CONCLUSIONS: Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).

Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial.

BACKGROUND: We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. METHODS: In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601. FINDINGS: Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. INTERPRETATION: In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. FUNDING: US National Cancer Institute.

Prostate-specific antigen response after short-term hormone therapy plus external-beam radiotherapy and outcome in patients treated on Radiation Therapy Oncology Group study 9413.

BACKGROUND: The objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes. METHODS: The phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA ≤0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure. RESULTS: For 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30). CONCLUSIONS: The current results indicated that failure to obtain a PSA-CR (PSA ≤0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation.