Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy.

BACKGROUND: Cancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. METHODS: A cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DISCUSSION: If successful, GEMS would be an option for a standardized APP-led survivorship care intervention. TRIAL REGISTRATION: ClinicalTrials.govNCT05006482, registered on August 9, 2021.

Differing mechanisms of atrial fibrillation in athletes and non-athletes: alterations in atrial structure and function.

AIMS: Atrial fibrillation (AF) is more common in athletes and may be associated with adverse left atrial (LA) remodelling. We compared LA structure and function in athletes and non-athletes with and without AF. METHODS AND RESULTS: Individuals (144) were recruited from four groups (each n = 36): (i) endurance athletes with paroxysmal AF, (ii) endurance athletes without AF, (iii) non-athletes with paroxysmal AF, and (iv) non-athletic healthy controls. Detailed echocardiograms were performed. Athletes had 35% larger LA volumes and 51% larger left ventricular (LV) volumes vs. non-athletes. Non-athletes with AF had increased LA size compared with controls. LA/LV volume ratios were similar in both athlete groups and non-athlete controls, but LA volumes were differentially increased in non-athletes with AF. Diastolic function was impaired in non-athletes with AF vs. non-athletes without, while athletes with and without AF had normal diastolic function. Compared with non-AF athletes, athletes with AF had increased LA minimum volumes (22.6 ± 5.6 vs. 19.2 ± 6.7 mL/m2, P = 0.033), with reduced LA emptying fraction (0.49 ± 0.06 vs. 0.55 ± 0.12, P = 0.02), and LA expansion index (1.0 ± 0.3 vs. 1.2 ± 0.5, P = 0.03). LA reservoir and contractile strain were decreased in athletes and similar to non-athletes with AF. CONCLUSION: Functional associations differed between athletes and non-athletes with AF, suggesting different pathophysiological mechanisms. Diastolic dysfunction and reduced strain defined non-athletes with AF. Athletes had low atrial strain and those with AF had enlarged LA volumes and reduced atrial emptying, but preserved LV diastolic parameters. Thus, AF in athletes may be triggered by an atrial myopathy from exercise-induced haemodynamic stretch consequent to increased cardiac output.

Sudden Death and Ventricular Arrhythmias in Athletes: Screening, De-Training and the Role of Catheter Ablation.

Athletes enjoy excellent health outcomes including greater longevity relative to non-athletic counterparts. Paradoxically, however, endurance athletic conditioning is associated with an increase in some arrhythmias. This review discusses the potential mechanisms for this paradox and strategies enabling early identification of potentially serious pathologies. Screening remains contentious due to the challenges of identifying relatively rare entities amongst a healthy cohort. The imperfect diagnostic accuracy of all current tests means that screening strategies have potential for harm through incorrect diagnoses as well as the potential for identification of important sub-clinical pathologies. Management of athletes at risk of ventricular arrhythmias and sudden cardiac death is similarly complex. There is much yet to learn about the specific patterns of ventricular arrhythmias in athletes, and the separation of benign from potentially life-threatening remains imperfect. There are some promising advances, however, such as specialised imaging modalities combined with improved electrophysiological diagnostics and therapeutics. Some unique clinical patterns are emerging to advance our understanding and management of athletes with ventricular arrhythmias, requiring specialised skillsets for evaluation and management.

State of the Art Review: Atrial Fibrillation in Athletes.

Exercise has substantial health benefits with pleomorphic vascular, metabolic, psychological and anti-neoplastic actions resulting in improved quality of life and longevity. Despite these many benefits, numerous studies have shown that endurance athletes are more likely to develop atrial fibrillation (AF) than non-athletes. The type, intensity and amount of sport appears to influence the risk of developing AF. Several endurance sport activities have been shown to increase the risk of developing AF but an excess in AF has not been shown in non-endurance sports. Furthermore, lifetime hours of participation appear to increase the risk of developing AF. Intriguingly, women appear relatively protected and an association between endurance sport and AF has not been clearly demonstrated amongst female endurance athletes. The mechanisms by which endurance sport promotes the development of AF are unclear. There are, however, a number of pathophysiological mechanisms which are known to increase the risk of AF in non-athletes which have correlates in athletes. These include structural remodelling of the left atrium, elevated left atrial pressure, inflammation, myocardial fibrosis, vagal tone, sinus bradycardia and genetic predisposition. In this article, we explore how some of these mechanisms may contribute to the development of AF in endurance athletes.

The role of cell-substrate interaction in regulating osteoclast activation: potential implications in targeting bone loss in rheumatoid arthritis.

Analysis of tissues retrieved from the bone-pannus interface from patients with rheumatoid arthritis (RA) and studies in animal models of inflammatory arthritis provide strong evidence that osteoclasts, the cells that are essential for physiological bone resorption, are responsible for articular bone destruction in RA. However, current treatments that specifically target osteoclast-mediated bone resorption in RA have not been successful in preventing bone erosions, and new therapeutic strategies are needed. It has been noted that, although osteoclast precursors are present within the bone microenvironment at sites of pathological bone resorption, cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface and adjacent calcified cartilage. These findings provide evidence that, in addition to requirements for specific cytokines, interaction of osteoclast precursors with these mineralised matrices results in activation of specific signal pathways and the induction of unique gene products that are essential for terminal osteoclast differentiation and activation. These studies are designed to define the gene products and signalling pathways regulated by bone and calcified cartilage, to identify new molecular targets and novel therapeutic approaches for preventing osteoclast-mediated joint destruction in RA and related forms of pathological bone loss.

Crystal ageing in irradiated ultra high molecular weight polyethylene.

Medical grade ultra high molecular weight polyethylene (UHMWPE) of two molecular weights has been gamma irradiated in air to give received doses of 3.5 and 10 Mrad and aged in air for 25 months. Differential scanning calorimetry and wide and small angle X-ray diffraction (WAX and SAX) techniques and transmission electron microscopy have been used to characterize the materials. Polymer from an orthopaedic component, retrieved 10 years after implantation, has been subjected to the same analytical programme. The X-ray diffraction data shows that following irradiation two events occur with time, first a crystal refinement process, indicated by pronounced sharpening of the SAX peak, and secondly growth of a new crystal population of reduced lamellae thickness compared to the original crystal structures, shown by the development of a bimodal SAX pattern. Following irradiation crystallinity increases with time and this second crystal population makes a significant contribution to that increase. The retrieved component shows full development of these processes. It is considered that these crystallographic changes with time are responsible for the observed time dependent changes in the mechanical properties of air irradiated UHMWPE.

Role of cell-matrix interactions in osteoclast differentiation.

Osteoclast and their mononuclear cell precursors are present within the bone microenvironment at sites of physiologic and pathologic bone resorption. Analysis of tissues from sites of bone resorption reveal that cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface. We hypothesize that in addition to cytokines, components of the bone matrix and specific cell surface receptors on osteoclasts and their precursors play an essential role in determining the genetic profile and functional properties of fully differentiated resorbing osteoclasts. We have employed expression profiling, with an in vitro model of matrix-dependent osteoclast differentiation, to identify the molecular pathways by which bone matrix-interactions induce terminal osteoclast differentiation and activation. In preliminary studies, we have identified unique genes and transcriptional pathways that are induced by interaction of osteoclast precursors with specific components of the mineralized bone matrix. The authenticity of the gene profiles, as markers of osteoclast differentiation and activation, have been provisionally validated using an in vivo animal bone implantation model and by examination of tissues from patients with specific forms of pathologic osteoclast-mediated bone resorption. The ultimate goal of our studies is to identify new molecular targets for inhibiting osteoclast-mediated bone loss in disorders of pathologic bone loss. The early work of Walker et al. (Walker 1972) in parabiotic animals, and the subsequent studies of Burger et al. (Burger, Van der Meer, van de Gevel, et al. 1982) using a co-culture model with fetal bone rudiments and bone marrow-derived cells, have helped to establish that osteoclasts are derived from macrophage precursors of colony forming unit-macrophage (CFU-M lineage). As such, they share a common hematopoietic origin with other CFU-M lineage cells, including tissue macrophages that populate the lung (alveolar macrophages), liver (Kupfer cells), synovium (synovial macrophages) and other organs. They also share a common lineage

Raising the ivory tower: the production of knowledge and distrust of medicine among African Americans.

African American distrust of medicine has consequences for treatment seeking and healthcare behaviour. Much work has been done to examine acute events (eg, Tuskegee Syphilis Study) that have contributed to this phenomenon and a sophisticated bioethics discipline keeps watch on current practices by medicine. But physicians and clinicians are not the only actors in the medical arena, particularly when it comes to health beliefs and distrust of medicine. The purpose of this paper is to call attention not just to ethical shortcomings of the past, but to the structural contexts of those events and the contributions and responsibilities of popular media and academic disciplines in the production of (often mythic) knowledge. We argue that ignoring context and producing inaccurate work has real impacts on health and healthcare, particularly for African Americans, and thus engenders ethical obligations incumbent on disciplines traditionally recognised as purely academic.

Plastid genome characterisation in Brassica and Brassicaceae using a new set of nine SSRs.

We report a new set of nine primer pairs specifically developed for amplification of Brassica plastid SSR markers. The wide utility of these markers is demonstrated for haplotype identification and detection of polymorphism in B. napus, B. nigra, B. oleracea, B. rapa and in related genera Arabidopsis, Camelina, Raphanus and Sinapis. Eleven gene regions (ndhB-rps7 spacer, rbcL-accD spacer, rpl16 intron, rps16 intron, atpB-rbcL spacer, trnE-trnT spacer, trnL intron, trnL-trnF spacer, trnM-atpE spacer, trnR-rpoC2 spacer, ycf3-psaA spacer) were sequenced from a range of Brassica and related genera for SSR detection and primer design. Other sequences were obtained from GenBank/EMBL. Eight out of nine selected SSR loci showed polymorphism when amplified using the new primers and a combined analysis detected variation within and between Brassica species, with the number of alleles detected per locus ranging from 5 (loci MF-6, MF-1) to 11 (locus MF-7). The combined SSR data were used in a neighbour-joining analysis (SMM, D (DM) distances) to group the samples based on the presence and absence of alleles. The analysis was generally able to separate plastid types into taxon-specific groups. Multi-allelic haplotypes were plotted onto the neighbour joining tree. A total number of 28 haplotypes were detected and these differentiated 22 of the 41 accessions screened from all other accessions. None of these haplotypes was shared by more than one species and some were not characteristic of their predicted type. We interpret our results with respect to taxon differentiation, hybridisation and introgression patterns relating to the 'Triangle of U'.

Building a retrospective collection in pharmacy: a brief history of the literature with some considerations for U.S. health sciences library professionals.

This paper argues that historical works in pharmacy are important tools for the clinician as well as the historian. With this as its operative premise, delineating the tripartite aspects of pharmacy as a business enterprise, a science, and a profession provides a conceptual framework for primary and secondary resource collecting. A brief history and guide to those materials most essential to a historical collection in pharmacy follows. Issues such as availability and cost are discussed and summarized in checklist form. In addition, a glossary of important terms is provided as well as a list of all the major U.S. dispensatories and their various editions. This paper is intended to serve as a resource for those interested in collecting historical materials in pharmacy and pharmaco-therapeutics as well as provide a history that gives context to these classics in the field. This should provide a rationale for selective retrospective collection development in pharmacy.

Endocarditis due to Salmonella.

We present a case of endocarditis caused by Salmonella in a patient with newly diagnosed diabetes and preexisting rheumatic heart disease. Despite sterilization of the blood with a fluoroquinolone and a third-generation cephalosporin, the patient required surgical intervention.

Infections during left ventricular assist device support do not affect posttransplant outcomes.

BACKGROUND: Although infections acquired during ventricular assist device support may increase the risk of infection and have an impact on transplant survival, their true posttransplant consequences remain to be determined. This study evaluates the impact of an outpatient program, newer devices, and an updated infection management protocol on infection-related patient outcomes after transplant. METHODS AND RESULTS: Eighty-six patients received a left ventricular assist device (LVAD) between June 1996 and June 1999. Fifty patients transplanted during the same period, without prior device support, were used as controls; they were matched to transplanted LVAD recipients by age, sex, diagnosis, and transplant date. The nature of and actuarial freedom from peritransplant and posttransplant infections were compared at 6 months after transplant; actuarial patient survival was compared at 3 years. Infection was defined as leukocytosis or leukopenia, with a positive culture requiring either medical or surgical intervention. Forty-four patients (51%) were successfully discharged home on LVAD support, and 61 (71%) were transplanted. A high incidence of infection during device support did not have an impact on pretransplant or posttransplant mortality, posttransplant infectious rate, or overall patient survival. Active infections at transplant also did not significantly influence 6-month mortality. In comparison, LVAD recipients had a lower freedom from infection than did controls (P:<0.05); however, 3-year survival did not differ: 79% and 87% for the LVAD and control groups, respectively. CONCLUSIONS: Although LVADs increase the risk of infection in the early posttransplant period, this appears not to have an impact on transplantability or patient survival and likely reflects effective infection control in both inpatient and outpatient settings.

Controlled clinical trial of a novel hemostatic agent in cardiac surgery. The Fusion Matrix Study Group.

BACKGROUND: We performed a prospective randomized trial to compare FloSeal Matrix (Fusion Medical Technologies, Inc, Mountain View, CA), a gelatin-based hemostatic sealant, with Gelfoam-Thrombin (Gelfoam, Pharmacia and Upjohn, Kalamazoo, MI; Thrombin, Gentrac Inc, Middeton, WI) (control group) to control perioperative bleeding. METHODS: A total of 93 patients undergoing cardiac operations were randomized into the FloSeal or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after applying the hemostatic agent. If bleeding stopped within 10 minutes, the application was considered to be successful. In the case of a failure, the surgeon could use any means preferred (except FloSeal) to achieve hemostasis. All bleeding sites in a patient were treated with the hemostatic agent to which the patient was randomized. Follow-up evaluation was performed at 12 to 36 hours and 6 to 8 weeks after operation. RESULTS: FloSeal stopped bleeding in 94% of the patients (first bleeding site only) within 10 minutes, compared to 60% in the control group (p = 0.001). At 3 minutes, successful hemostasis was achieved in 72% of the FloSeal group compared with 23% in the control group (p = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: FloSeal Matrix demonstrated efficacy superior to that of Gelfoam-Thrombin and had a safety profile similar to that of Gelfoam-Thrombin when used as a topical hemostatic agent during cardiac surgery procedures.

Telephone medicine for internists.

The role of the telephone in medical practice is important, but often problematic. Mistakes in telephone diagnosis and triage can have severe consequences. An effective office system can reduce liability risks, and in some cases telephone contact can substitute for office visits. Internists feel unprepared to provide telephone care. Therefore, residency education needs to focus on documentation, consultant availability, and performance feedback. Research should focus on improving outcomes, reimbursement issues, and technologic advances. This article describes internists' telephone interactions with ambulatory patients, preparation for telephone medicine, and aspects of office telephone systems and makes comparisons with other primary care fields.