Feasibility and efficacy of a remotely delivered fall prevention exercise program for community-dwelling older adults with cancer: Protocol for the STABLE trial.

Falls are a major issue in older adults with cancer due to the effects of cancer and its treatments. Ample evidence in the general population of older adults has demonstrated the effectiveness of strength and balance training in reducing fall rates in older adults. However, data on effective fall prevention interventions in the oncology setting are lacking. The objective of this study is to evaluate the feasibility and efficacy of a remotely delivered, partially-supervised, resistance and balance training program on lower body strength, balance, and falls in community-dwelling older adults with cancer. The proposed study is an observer-blinded, parallel group (intervention group vs. control group) randomized controlled trial (ClinicalTrials.gov Identifier: NCT04518098). This study will recruit 74 eligible community-dwelling older adults with cancer from a comprehensive cancer centre. Intervention includes a remotely delivered exercise program for 3 months. Outcome measures include feasibility measures, lower body strength, balance, and fall rates. Research ethics approval has been granted by the Biomedical Research Ethics Boards of the University of Saskatchewan. If found effective, findings from this study will inform a subsequent, phase III definitive trial, with the ultimate goal to reduce falls and reduce impact on cancer treatment. Study findings will be disseminated through presentation at community level and scientific conferences, and in scientific journals. Trial registration: ClinicalTrials.gov identifier: NCT04518098.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Feasibility of a Remotely Delivered Strength and Balance Training Program for Older Adults with Cancer.

Falls are a major issue among older adults with cancer and lead to interruptions in cancer treatment. Resistance and balance training can prevent falls in older adults, but minimal evidence is available regarding the older cancer population, who often have unique risk factors. We used a pre-post design to assess the feasibility of a remotely delivered exercise program that progressed in difficulty and its efficacy on lower body strength, balance, and falls in older adults with cancer who had prior in-person exercise experience. Twenty-six older adults with cancer completed the intervention. Attendance rate for the virtual component was 97.6% and for the independent component was 84.7%. Participants perceived the program as rewarding and enjoyable (100%), felt this program prepared them to exercise on their own (92%), were confident to continue exercising on their own (81%), and would recommend the program to other patients (100%). The median balance score at baseline and end-of-study was 4 (IQR = 0). The median chair-stand time decreased from 9.2 s (IQR = 3.13) to 7.7 s (IQR = 4.6). A statistically significant difference in lower body strength (r = 0.68, p = 0.001) was detected post-intervention. The findings from this study can inform the design of a larger randomized trial.

Oncology clinic nurses' attitudes and perceptions regarding implementation of routine fall assessment and fall risk screening: A survey study.

Falls in older adults with cancer are often under-recognized and under-reported. The objective of this study was to explore oncology clinic nurses' willingness and perceived barriers to implement routine falls assessment and falls screening in their practice. Nurses working in outpatient oncology clinics were invited to complete an online survey. Data were analyzed using descriptive statistics and sorted into thematic categories. The majority of respondents indicated willingness to routinely ask older patients about falls (85.7%) and screen for fall risks (73.5%). The main reasons for unwillingness included: belief that patients report falls on their own, lack of time, and lack of support staff. Findings from this study show many oncology nurses believe in the importance of routine fall assessment and screening and are willing to implement them routinely, although falls are not routinely asked about or assessed. Future work should explore strategies to address barriers nurses face given the implications of falls amongst this vulnerable population.

Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells.

PURPOSE: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. MATERIALS AND METHODS: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. RESULTS: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). CONCLUSIONS: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.

An enigmatic Hawaiian moth is a missing link in the adaptive radiation of Schiedea.

Shifts in pollination may drive adaptive diversification of reproductive systems within plant lineages. The monophyletic genus Schiedea is a Hawaiian lineage of 32 extant species, with spectacular diversity in reproductive systems. Biotic pollination is the presumed ancestral condition, but this key element of the life history and its role in shaping reproductive systems has remained undocumented. We observed floral visitors to two species of Schiedea and conducted field experiments to test pollinator effectiveness. We used choice tests to compare attraction of pollinators to species hypothesized to be biotically vs wind-pollinated. Pseudoschrankia brevipalpis (Erebidae), a recently described moth species known only from O'ahu, visited hermaphroditic Schiedea kaalae and S. hookeri and removed nectar from their unique tubular nectary extensions. Pseudoschrankia brevipalpis effectively pollinates S. kaalae; single visits to emasculated flowers resulted in pollen transfer. In choice tests, P. brevipalpis strongly preferred these hermaphroditic species over two subdioecious species capable of wind pollination. A shift from biotic to abiotic pollination is clearly implicated in the diversification of reproductive systems within Schiedea. Abundant pollination by a previously unknown native moth in experimental and restored populations suggests the potential for restoration to re-establish native plant-pollinator interactions critical for production of outcrossed individuals with high fitness.

Qualitative analysis of Medicare claims in the last 3 years of life: a pilot study.

OBJECTIVES: To study end-of-life care of a representative sample of older people using qualitative interpretation of administrative claims by clinicians and to explore whether this method yields insights into patient care, including continuity, errors, and cause of death. DESIGN: Random, stratified sampling of decedents and all their Medicare-covered healthcare claims in the 3 years before death from a 5% sample of elderly fee-for-service beneficiaries, condensation of all claims into a chronological clinical summary, and abstraction by two independent clinicians using a standardized form. SETTING: United States. PARTICIPANTS: One hundred Medicare fee-for-service older people without disability or end-stage renal disease entitlement who died in 1996 to 1999 and had at least 36 months of continuous Part A and Part B enrollment before death. MEASUREMENTS: Qualitative narrative of the patient's medical course; clinician assessment of care continuity and apparent medical errors; cause, trajectory, and place of death. RESULTS: The qualitative narratives developed by the independent abstracters were highly concordant. Clinicians felt that 75% of cases lacked continuity of care that could have improved the quality of life and the way the person died, and 13% of cases had a medical error identified by both abstracters. Abstracters disagreed about assignment of a single cause of death in 28% of cases, and abstracters and the computer algorithm disagreed in 43% of cases. CONCLUSION: Qualitative claims analysis illuminated many problems in the care of chronically ill older people at the end of life and suggested that traditional vital statistics assignation of a single cause of death may distort policy priorities. This novel approach to claims review is feasible and deserves further study.

Medicare program expenditures associated with hospice use.

BACKGROUND: Hospice providers contend that enrollment reduces the cost of the Medicare programs, but estimates of effects are dated, methodologically limited, and focused on persons with cancer. OBJECTIVE: To estimate the effects of hospice care on Medicare program payments during the last year of life from 1996 to 1999 within cohorts defined by age and diagnosis. DESIGN: Retrospective cohort. SETTING: Deceased Medicare enrollees. PARTICIPANTS: Elderly Medicare fee-for-service beneficiaries who received 36 months of continuous Part A and B coverage before death during 1996 to 1999 (n = 245 326). Age- and condition-specific (cancer or noncancer and principal condition) cohorts were defined. MEASUREMENTS: Medicare expenditures in the last year of life, as a total figure and by service type. The cost effects of hospice were estimated by using linear regression within the cohorts for hospice enrollees compared with nonenrollees after adjustment for propensity to use hospice, gender, race, enrollment in Medicaid, urban setting, duration of illness, comorbid conditions, low use of Medicare, nursing home residence, and year of death. RESULTS: Adjusted mean expenditures were 4.0% higher overall among hospice enrollees than among nonenrollees. Adjusted mean expenditures were 1% lower for hospice enrollees with cancer than for patients with cancer who did not use hospice. Savings were highest (7% to 17%) among enrollees with lung cancer and other very aggressive types of cancer diagnosed in the last year of life. Expenditures for hospice enrollees without cancer were 11% higher than for nonenrollees, ranging from 20% to 44% for patients with dementia and 0% to 16% for those with chronic heart failure or failure of most other organ systems. Hospice-related savings decreased and relative costs increased with age. CONCLUSION: Hospice enrollment correlates with reduced Medicare expenditures among younger decedents with cancer but increased expenditures among decedents without cancer and those older than 84 years of age. Future studies should assess the effects of hospice on quality and on expenditures from all payment sources.

Community-based chlamydia and gonorrhea screening through the United States mail, San Francisco.

BACKGROUND: Because gonococcal and chlamydial infections are often asymptomatic, disease control requires population-based screening. This report describes the feasibility of home-based testing for sexually transmitted diseases (STDs) and of specimen transport via the US mail. GOAL: This project sought to establish the efficacy and acceptability to the public of screening by means of urine kits made available in public places and mailed in for STD testing. STUDY DESIGN: Self-selected community participants obtained STD test kits from local businesses, collected urine specimens at home, and mailed kits to the health department for nucleic acid amplification testing. RESULTS: Participants picked up 209 test kits and returned 80 (38%): 3 (3.8%) of 76 were positive for gonorrhea and 1 (1.3%) of 76 was positive for chlamydia. The majority (95%) of participants were white gay men. The cost of specimen collection and transport was similar to that of other population-based screening programs. CONCLUSION: Using the mail for home-based testing for gonorrhea and chlamydia was feasible and may be a useful addition to STD control efforts.