Point of care testing for hepatitis C in the priority settings of mental health, prisons and drug & alcohol facilities - the PROMPt Study.

BACKGROUND: A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care-testing (POCT) on testing rates, linkage to care, treatment and acceptability of testing in three priority settings in Australia. METHODS: Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service (MHS), and inpatient alcohol and other drug (AOD) unit-between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert® HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control. RESULTS: 1,549 participants received a HCV antibody test with 17% (264/1,549) receiving a positive result, of which 21% (55/264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by three-fold (RR:2.57 95% CI: 2.32, 2.85) for HCV antibody testing and four-fold (RR:1.62; 95% CI:1.31, 2.01) for RNA testing. Treatment uptake was higher during the POCT intervention (86%, 47/55; P=0.010) compared to the historical controls (61%, 27/44). CONCLUSIONS: This study demonstrated across three settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake linkage to care. The testing model was highly acceptable for most participants. CLINICAL TRIAL REGISTRATION: ACTRN-12621001578897.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RESULTS: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38). CONCLUSION: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Undergraduate College Pathway Programs Designed to Attract and Matriculate Students from Underrepresented Groups into Medicine.

OBJECTIVES: Undergraduate college pathway (or pipeline) programs support students' interests as they explore advanced degree and career pathways. Many programs aim to diversify the medical workforce by reducing barriers that may have otherwise prevented desired academic and career goals; however, variability in structure, expectations, benefits, and outcome data exist. This systematic review was conducted to identify and evaluate undergraduate college pathway programs designed to increase the diversity of medical school matriculants. METHODS: We searched Ovid Medline, PsycInfo, Scopus, and the Education Resources Information Center for peer-reviewed, original research publications (1996-2019) describing US pathway/pipeline programs designed for undergraduate-level college students from underrepresented groups to apply and enter medical school. Data extraction included application processes, participant demographics, curricular components, social support systems, mentorship, funding, and program/participant outcomes. We reviewed the journal impact factor to inform us about where articles are being published. RESULTS: Our full-text review included 137 articles; 25 articles met the inclusion criteria. All of the papers were descriptive, requiring an application, minimum grade point average, letters of recommendation, and personal statements. All of the programs aimed to diversify medicine, yet some could not request identification of race/ethnicity because of changes in affirmative action or legal restrictions when reporting demographics. Women represented the majority of enrollees. The program length varied; all reported having one or a combination of academic enrichment, research, field observation/experience, and mentorship. All of the programs included career development and various supplemental social supports. Only two programs provided comparison data; four reported no outcomes. CONCLUSIONS: Pathway programs support the acquisition and enhancement of professional skills. Lacking longitudinal or comparison data leads to questions of the long-term impact on diversifying the medical workforce. This article highlights a need for rigorous data collection methods and transparent reporting of participant outcomes to inform programmatic efficacy.

Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. METHODS: We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. RESULTS: Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. CONCLUSIONS: Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

Suboptimal COVID-19 vaccine uptake among hospitalised patients: an opportunity to improve vulnerable, hard-to-reach population vaccine rates.

BACKGROUND: COVID-19 vaccination represents a key preventative part of the Australian public health approach to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hospital inpatients are frequently high risk for severe COVID-19 and death. Anecdotes of high-risk inpatients being unvaccinated and a lack of electronic medical record (EMR) visibility of COVID-19 vaccination status prompted the present study as these patients could represent a risk to themselves, staff, other patients and service provision. AIMS: To determine the uptake of COVID-19 vaccine among inpatients at an adult Australian tertiary public hospital and identify reasons for non-vaccination. METHODS: A point-prevalence study of patient-reported COVID-19 vaccine status was conducted on 26 October 2021 through an in-person interview with collection of demographic factors and reasons for non-vaccination. RESULTS: Of 368 (68% of inpatients) participants, 280 (76%) reported receiving at least one COVID-19 vaccine dose. Vaccination status was associated with older age, having received the flu vaccine, being born in Australia and not requiring an English-language interpreter. The majority (88%) of participants had at least one comorbid risk factor for severe COVID-19. Of the unvaccinated (n = 88), 67% were willing to be vaccinated with 54% of those indicating vaccination in hospital would be helpful and 42% requesting approval from their doctor. CONCLUSIONS: Vaccine uptake in our cohort is suboptimal. Existing public health programmes have failed to reach this high-risk, vulnerable population. Changes to the national vaccination strategy to include a parallel inhospital programme for all hospital encounters and target culturally and linguistically diverse individuals might improve uptake among this high-risk, hard-to-reach group of patients.

Racial Disparities in the Emergency Department Evaluation of Adolescent Girls.

OBJECTIVE: Racial disparities and differences exist in emergency care. Obtaining a sexual history is standard of care for adolescents with abdominal pain. Testing for sexually transmitted infections (STIs) and pregnancy should be based on historical findings. The objective of this study was to determine whether differential care was provided to adolescent female patients with abdominal pain based on patient race or healthcare provider characteristics by evaluating the documentation of sexual history, STI testing, and pregnancy testing. METHODS: This was a retrospective chart review of female patients between the ages of 14 and 18 years with abdominal pain presenting to a pediatric emergency department. Patient and provider characteristics, sexual history documentation, STI, and pregnancy testing were abstracted. Data were analyzed using χ 2 test and logistic regression model. RESULTS: Eight hundred eighty-six encounters were included in the analysis. Median patient age was 16 years (range, 14-18 years); 359 (40.5%) were non-White. Differential care was provided. Non-White patients compared with White patients were more likely to have a documented sexual history (59.9% vs 44.0%, P < 0.001), STI testing (24.8% vs 7.8%, P < 0.001), and pregnancy testing (76.6% vs 66.2%, P < 0.001). Among sexually active female patients, the racial disparity for STI testing persisted ( P = 0.010). Provider type and sex did not result in differences in sexual history documentation, STI, or pregnancy testing for non-White compared with White patients ( P > 0.05). CONCLUSIONS: Differential care was provided to non-White adolescents with abdominal pain compared with White adolescents. They were more likely to have a documented sexual history, STI testing, and pregnancy testing. Healthcare provider characteristics did not impact patient care. This racial disparity resulted in better medical care for non-White adolescents, but this may be the consequence of underlying implicit bias.

Xerostomia and polypharmacy among dependent older New Zealanders: a national survey.

BACKGROUND: Medication-induced xerostomia is common in older people. We investigated medication use and xerostomia in dependent older New Zealanders. METHODS: Medication and xerostomia data analysed from a nationally representative survey of dependent older people. Automatic interaction detection analysis identified medications combinations most strongly associated with xerostomia, and then xerostomia was modelled. RESULTS: Just over half were taking five to nine different medications; one in five was taking 10+. Xerostomia prevalence (29.4%; 95% confidence interval 26.5, 32.5) was higher among the latter and lowest in psychogeriatric patients. After controlling for age and sex, it was higher among people taking any antidepressant, and higher still with a tricyclic antidepressant and either a steroid or an anticholinergic, or among people taking a bronchodilator without prophylactic aspirin. CONCLUSIONS: Health practitioners should work together to ensure that those with xerostomia are managed in a timely and appropriate manner. Medication review is an important component of that.

Dentition and nutritional status of aged New Zealanders living in aged residential care.

BACKGROUND: Previous studies of the nutritional status of older individuals have used measures such as plasma vitamin and mineral levels, which can be difficult to interpret. The relationship between nutrition and dentition has been limited to studying exposures such as the number of posterior occluding pairs of teeth, edentulousness, and the number of natural teeth. OBJECTIVES: To investigate the association between dentition status and nutritional status in a national survey of older New Zealanders living in aged residential care facilities. MATERIAL AND METHODS: Secondary analysis of clinical oral status and nutrition data collected in 2012 in New Zealand's Older People's Oral Health Survey. The validated Mini Nutritional Assessment short format was used to categorize participants as "normal nutritional status," "at risk of malnutrition" or "malnourished." RESULTS: Just under half of older New Zealanders living in aged residential care facilities were classified as either at risk of malnutrition or malnourished (with about one in sixteen in the latter category). The prevalence of malnutrition was higher among those in hospital-level and psychogeriatric-level care, as well as in those of high socioeconomic status. Individuals who were at risk of malnutrition had the most untreated dental caries and untreated coronal caries. Relative to their counterparts in nursing-home-level care, dentate individuals in hospital-level care were 2.4 times-and those in psychogeriatric-level care were 2.8 times-as likely to be malnourished or at risk of it. CONCLUSIONS: Just under half of the New Zealanders living in aged residential care were at risk of malnutrition or were malnourished. Greater experience of untreated dental caries was associated with a higher rate of being malnourished or at risk of it. Poorer cognitive function and greater dependency were important risk indicators for malnutrition.

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.

BACKGROUND: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS: A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS: Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476 , and Current Controlled Trials number, ISRCTN78818544 .).

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Maternal complications following open and fetoscopic fetal surgery: A systematic review and meta-analysis.

OBJECTIVE: To establish maternal complication rates for fetoscopic or open fetal surgery. METHODS: We conducted a systematic literature review for studies of fetoscopic or open fetal surgery performed since 1990, recording maternal complications during fetal surgery, the remainder of pregnancy, delivery, and after the index pregnancy. RESULTS: One hundred sixty-six studies were included, reporting outcomes for open fetal (n = 1193 patients) and fetoscopic surgery (n = 9403 patients). No maternal deaths were reported. The risk of any maternal complication in the index pregnancy was 20.9% (95%CI, 15.22-27.13) for open fetal and 6.2% (95%CI, 4.93-7.49) for fetoscopic surgery. For severe maternal complications (grades III to V Clavien-Dindo classification of surgical complications), the risk was 4.5% (95% CI 3.24-5.98) for open fetal and 1.7% (95% CI, 1.19-2.20) for fetoscopic surgery. In subsequent pregnancies, open fetal surgery increased the risk of preterm birth but not uterine dehiscence or rupture. Nearly one quarter of reviewed studies (n = 175, 23.3%) was excluded for failing to report the presence or absence of maternal complications. CONCLUSIONS: Maternal complications occur in 6.2% fetoscopic and 20.9% open fetal surgeries, with serious maternal complications in 1.7% fetoscopic and 4.5% open procedures. Reporting of maternal complications is variable. To properly quantify maternal risks, outcomes should be reported consistently across all fetal surgery studies.

Oral status, cognitive function and dependency among New Zealand nursing home residents.

OBJECTIVES: To investigate clinical oral disease and its association with cognitive function and dependency among older New Zealanders in residential aged care. MATERIAL AND METHODS: National survey of oral health in aged residential care throughout New Zealand. We classified residents into 1 of 3 levels of care: "low dependency care (or assisted living)"; "high dependency care"; or "specialist dementia care/psychogeriatric care." The Abbreviated Mental Test characterised cognitive function as "unimpaired" (scores of 7-10), "moderately impaired" (4-6) or "severely impaired" (0-3). Intra-oral examinations were conducted, along with a computer-assisted personal interview. RESULTS: Most of the 987 clinically examined participants were either at low or high dependency care level, with another 1 in 6 in psychogeriatric care. Almost half overall had severely impaired cognitive function. Just under half of the sample had 1 or more natural teeth remaining. Negative binomial regression modelling showed that the number of carious teeth was lower among women and higher among those who were older, those with more teeth and in those with severely impaired cognitive function. Oral debris scores (representing plaque biofilm and other soft deposits on teeth) were higher in men, those with more teeth, and in those with severely impaired cognitive function. CONCLUSIONS: Impaired cognitive function is a risk indicator for both dental caries and oral debris in aged residential care.

Jugular venipuncture and other innovative approaches to phlebotomy among people who inject drugs.

In their recent paper on patient experiences of accessing phlebotomy services in hospital outpatient clinics, Clements and colleagues state that there is a real need to better understand the responses of people who inject drugs to phlebotomy. They discuss the reasons why people who inject drugs might not be accessing healthcare services, especially in relation to treatment for hepatitis C. Their research is a welcome addition to the literature that emphasizes the stigma and discrimination faced by people who inject drugs, including within healthcare settings, and outlines the need to promote effective partnerships between healthcare workers and patients so as to deliver the best health outcomes.

Laterality of Radiation Therapy in Breast Cancer is Not Associated With Increased Risk of Coronary Artery Disease in the Contemporary Era.

Purpose: External beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesized that there is no difference in the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left versus right-sided radiation. Methods and Materials: For the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022. CAD was identified using a homogenous metric across multiple studies included. We computed the risk ratio (RR) for included studies using a random effects model. For the institutional cohort portion of our study, we selected high cardiovascular-risk patients who received diagnoses of BC between 2010 and 2022 if they met our inclusion criteria. We performed a Cox proportional hazards model with stepwise adjustment. Results: A pooled random effects model with 9 studies showed that patients with left-sided BC receiving EBRT had a 10% increased risk of CAD when compared with patients with right-sided BC receiving EBRT (RR, 1.10; 95% CI, 1.02-1.18; P = .01). However, subgroup analysis of 6 studies that included patients diagnosed after 1980 did not show a significant difference in CAD based on BC laterality (RR, 1.07; 95% CI, 0.95-1.20; P = .27). For the institutional cohort portion of the study, we found that patients with left-sided BC who received EBRT did not have a significantly higher risk of CAD when compared with their right-sided counterparts (hazard ratios [HR], 0.73; 95% CI, 0.34-1.54; P = .402). Conclusions: Our study suggests a historical trend of increased CAD in BC patients receiving left-sided EBRT. Data from patients diagnosed after 2010 in our institutional cohort did not show a significant difference, emphasizing that modern EBRT regimens are safe, and laterality of BC does not affect CAD outcomes in the short term after a BC diagnosis.

The Almost Perfect Scale in medical students: factor analysis, measurement invariance, and profile analysis.

Incoming medical students at a private midwestern medical school are routinely surveyed at the time of matriculation on wellness measures, one of which is the Almost Perfect Scale - Revised (APS-R). An 8-item subset of this 23-item scale has been suggested as an alternative perfectionism measure, called the Short Almost Perfect Scale (SAPS). To confirm the within-network and between-network construct validity of both scales in our population, responses in 592 matriculating medical students from the years 2020-2022 were analyzed using both versions of this scale. Confirmatory factor analysis found the items significantly measured the construct of perfectionism in the SAPS scale, but not the APS-R. The APS-R was not analyzed further. SAPS was analyzed for measurement invariance (MI) and was equivocal for gender at the scalar level; differential item functioning indicated that any MI effect was small. Latent profile analysis was inconclusive in our sample, possibly because our students' scores on the latent variable "standards" were consistently higher than previously reported. We recommend that the SAPS be used rather than the APS in medical students, that gender differences be analyzed with caution, and that profiles of types of perfectionists not be utilized in this population without further investigation. Finally, we suggest that the discrepancy scale alone may be a better indicator of perfectionism in this population of high achievers.

REACH: A Required Curriculum to Foster the Well-Being of Medical Students.

PROBLEM: The extent of medical student unwellness is well documented. Learner distress may impact patient care, workforce adequacy, and learners' performance and personal health. The authors describe the philosophy, structure, and content of the novel REACH (Recognize, Empathize, Allow, Care, Hold each other up) curriculum and provide a preliminary evaluation. APPROACH: The REACH curriculum is a mandatory, longitudinal well-being curriculum for first- and second-year medical students at the Medical College of Wisconsin (MCW) designed to prepare them for the emotional life of being a physician. The curriculum uses a framework, core concepts, and skills from the field of trauma stewardship. It builds on effective medical student well-being interventions (e.g., mindfulness-based training) and the sharing of personal stories by instructors during didactic and small-group sessions that are integrated into the regular MCW curriculum. During the first 2 years of implementation (2018-2019 and 2019-2020), the curriculum was evaluated using mid- and postcurriculum student surveys. OUTCOMES: Over 700 students have completed the REACH curriculum as of March 2022. Overall, most students who responded to the surveys in 2018-2020 reported that they felt the REACH curriculum material was important, that the curriculum met their expectations for a quality medical school course, and that they would recommend other schools incorporate a similar curriculum. Respondents to the 2019-2020 postcurriculum survey indicated the REACH curriculum helped them develop self-care (84% [85/101]), mindfulness (76% [76/101]), and help-seeking (71% [72/101]) skills. NEXT STEPS: The initial outcomes show that integrating a mandatory well-being curriculum is feasible and acceptable to medical students. The authors plan to examine the relationships between student-reported well-being metrics, academic and clinical performance data, and professional identity formation. They are also prototyping electronic dashboards that will allow students to interact with their well-being data to promote timely help-seeking and behavior change.

Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial.

PURPOSE: CHHiP is a randomized trial evaluating moderately hypofractionated radiation therapy for treatment of localized prostate cancer. Of all participants, 97% of them had concurrent short-course hormone therapy (HT), either luteinizing hormone-releasing hormone analog (LHRHa) or 150 mg of bicalutamide daily. This exploratory analysis compares efficacy and side effects in a nonrandomized comparison. METHODS AND MATERIALS: In our study, 2700 patients received LHRHa and 403 received bicalutamide. The primary endpoint was biochemical/clinical failure. Groups were compared with Cox regression adjusted for various prognostic factors and stratified by radiation therapy dose. A key secondary endpoint was erectile dysfunction (ED) assessed by clinicians (using scores from Late Effects on Normal Tissues: Subjective/Objective/Management [LENT-SOM] subjective erectile function for vaginal penetration) and patients (single items within the University of California-Los Angeles Prostate Cancer Index [UCLA PCI] and Expanded Prostate Cancer Index Composite [EPIC]-50 questionnaires) at 2 years and compared between HT regimens by χ2 trend test. RESULTS: Bicalutamide patients were significantly younger (median 67 vs 69 years LHRHa). Median follow-up was 9.3 years. There was no difference in biochemical or clinical failure with an adjusted hazard ratio or 0.97 (95% confidence interval, 0.77-1.23; P = .8). At 2 years, grade ≥2 LENT-SOM ED was reported in significantly more LHRHa patients (313 out of 590; 53%) versus bicalutamide (17 out of 68; 25%) (P < .0001). There were no differences in ED seen with UCLA-PCI and EPIC-50 questionnaires. CONCLUSIONS: In this nonrandomized comparison, there was no evidence of a difference in efficacy according to type of HT received. Bicalutamide preserved clinician assessed (LENT-SOM) erectile function at 2 years but patient-reported outcomes were similar between groups.

Quality Improvement Project to Improve the Timeliness of Care for Children With Testicular Torsion in the Emergency Department.

Introduction: Testicular torsion (TT) is a urologic emergency that requires timely diagnosis and surgery. We noted variation in the door-to-detorsion times for patients with TT at our institution and our orchiectomy rate was 25.8%. We aimed to decrease the mean door-to-detorsion time from 124.6 to 114.6 minutes or less over 12 months. Methods: A multidisciplinary team of pediatric emergency medicine, radiology, urology physicians, and nurses, was formed. Our key drivers were use of Testicular Workup for Ischemia and Suspected Torsion (TWIST) score, prompt urology consultation, and efficient transfer from emergency department (ED) to operating room. Our process measures were TWIST score documentation rate and early urology consultation rate, outcome measures were door-to-detorsion time and orchiectomy rate, and balancing measure was ultrasound utilization rate. Early urology consultation occurred when the ED provider documented telephone communication with urology, immediately after placing a testicular doppler ultrasound (TDUS) order and before TDUS result. Results: Over 2 years, 45 cases of TT were diagnosed. TWIST score documentation was implemented and was sustained at 78%. This improved early urology consultations from 40% to 60%. The mean door-to-detorsion time improved from 124.6 to 114.2 minutes. There was no reduction in the orchiectomy rate or TDUS utilization rate. Conclusions: A quality improvement project to improve the timeliness of care for children with TT resulted in expedited ED care but did not impact the orchiectomy rate.

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (P = .53), disease-free survival (P = .21), or locoregional failure (P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.

SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.