Pain, Opioid Analgesics, and Cognition: A Conceptual Framework in Older Adults.

Chronic pain is highly prevalent in older adults and is associated with poor functional outcomes. Furthermore, opioid analgesics are commonly utilized for the treatment of pain in older adults despite well-described adverse effects. Importantly, both chronic pain and opioid analgesics have been linked with impairments in cognitive function, though data are limited. In this manuscript we summarize the evidence and critical knowledge gaps regarding the relationships between pain, opioid analgesics, and cognition in older adults. Furthermore, we provide a conceptual framework to guide future research in the development, implementation, and evaluation of strategies to optimize analgesic outcomes in older adults while minimizing deleterious effects on cognition.

A Nurse-Led Algorithm for Diagnosing Urinary Tract Infection in Homebound Older Adults.

PURPOSE: We designed a nurse-led algorithm to standardize urinary tract infection (UTI) diagnosis for older adults receiving home-based medical care. Aims of this pilot quality improvement study were to reduce the frequency of empiric antibiotic therapy initiated without a urinalysis and urine culture (UA/UC) first being obtained, reduce antibiotic use without a concomitant increase in emergency department (ED) visits or hospital admissions, and ensure stakeholders' satisfaction with algorithm use. METHOD: A nurse-led diagnostic algorithm was designed and pilot-tested to address challenges and standardize diagnosis of UTI in a population of homebound older adults. RESULTS: In pre/post data analysis, algorithm implementation was associated with improved frequency of obtaining UA/UC before empiric antibiotic therapy was initiated, but the overall rate of antibiotic use for UTI did not decrease. No increase in ED or hospital admissions was identified. CONCLUSION: Use of a diagnostic algorithm for UTI among homebound older adults was associated with reduced frequency of empiric antibiotic initiation for suspected UTI without a UA/UC first being obtained. More rigorous study is needed to confirm and expand on these findings. [Research in Gerontological Nursing, 17(2), 92-97.].

Targeted therapy in advanced urothelial carcinoma.

Urothelial carcinoma (UC) is a common and deadly cancer in the United States. While molecularly targeted therapies have been integrated into the standard-of-care management of other solid tumors in recent years, the use of targeted therapy in UC has lagged behind. Accordingly, the management of advanced disease, along with outcomes, has remained largely unchanged for the past 2 decades. Despite the lack of new agents in the clinic, preclinical and early clinical studies have demonstrated that numerous potentially"targetable" molecular pathways exist, including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2/neu), and insulin-like growth factor 1 receptor (IGF1R) pathways. This review focuses on targeted therapies related to these pathways of interest for the treatment of advanced UC, describing the evidence to support further investigation of these approaches. Notably, the identification and validation of new agents will only occur through accrual to urothelial cancer trials designed to answer these questions, which will require the support of the entire urologic community.

Role of senescence in the chronic health consequences of COVID-19.

While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection). There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19. The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections. Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection. Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections. These processes may contribute to increased risk for long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.

Design and Implementation of a Skilled Nursing Facility COVID-19 Unit.

Coronavirus disease 2019 (COVID-19) has challenged the health care system's capacity to care for acutely ill patients. In a collaborative partnership between a health system and a skilled nursing facility (SNF), we developed and implemented an SNF COVID-19 unit to allow expedited hospital discharge of COVID-positive older adults who are clinically improving, and to provide an alternative to hospitalization for those who require SNF care but do not require or necessarily desire aggressive disease-modifying interventions.

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.

Prevention, Diagnosis, and Management of Chronic Wounds in Older Adults.

Chronic wounds are common, disproportionately affect older adults, and are likely to be encountered by providers across all specialties and care settings. All providers should be familiar with basic wound prevention, identification, classification, and treatment approach, all of which are outlined in this article.

Palliative Medicine and Preparedness Planning for Patients Receiving Left Ventricular Assist Device as Destination Therapy-Challenges to Measuring Impact and Change in Institutional Culture.

CONTEXT: Although left ventricular assist devices as destination therapy (DT-LVAD) can improve survival, quality of life, and functional capacity in well-selected patients with advanced heart failure, there remain unique challenges to providing quality end-of-life care in this population. Palliative care involvement is universally recommended, but how to best operationalize this care and measure success is unknown. OBJECTIVES: To characterize the process of preparedness planning (PP) for patients receiving DT-LVAD at our institution and better understand opportunities for quality improvement or procedural transferability. METHODS: Retrospective review of 107 consecutive patients undergoing DT-LVAD implantation at a single institution between 2009 and 2013. Information regarding demographics, advance care planning, and mortality was abstracted from the medical record and analyzed. Findings were compared with a historical cohort who received DT-LVAD implantation at the same institution before the development of PP (2003-2009). RESULTS: Mean age of patients receiving DT-LVAD was 64.3 years (SD ± 10.7). At last follow-up, 46 patients (43%) had died. Mean post-DT-LVAD survival in this group was 1.1 years (SD ± 1.2). Eighty-nine percent of patient had palliative care consultation before implantation, and 70% completed PP. Although 66% of patients completed an advance directive (AD) preimplantation, only two ADs (2.8%) specifically mentioned DT-LVAD and none addressed core elements of PP. AD completion rates improved from 47% before our policy on PP (P = 0.012). CONCLUSION: A disconnect was evident between the rigor of PP discussions and the content of ADs in the medical record. We urge that future efforts focus on narrowing this gap.

Improved resident physician confidence with advance care planning after an ambulatory clinic intervention.

Many primary care providers feel uncomfortable discussing end-of-life care. The aim of this intervention was to assess internal medicine residents' advance care planning (ACP) practices and improve residents' ACP confidence. Residents participated in a facilitated ACP quality improvement workshop, which included an interactive presentation and chart audit of their own patients. Pre- and postintervention surveys assessed resident ACP-related confidence. Only 24% of the audited patients had an advance directive (AD), and 28% of the ACP-documentation was of no clinical utility. Terminally ill patients (odds ratio 2.8, P < .001) were more likely to have an AD. Patients requiring an interpreter were less likely to have participated in ACP. Residents reported significantly improved confidence with ACP and identified important training gaps. Future studies examining the impact on ACP quality are needed.

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer.

BACKGROUND: The aim of the study was to measure plasma levels of the vascular endothelial growth factors (VEGF) A and D in serially collected blood specimens from non-localized prostate cancer (PCa) subjects. METHODS: Plasma VEGF A and D levels were measured in two serial specimens 3-6 months apart in two groups of non-localized stage PCa patients. Group 1 was comprised of patients with biochemical relapse after localized PCa treatments and/or patients with clinically metastatic hormone-sensitive stage PCa prior to receiving hormonal therapy. Group 2 included patients failing hormonal therapy for non-localized hormone-sensitive stage PCa. VEGF A and D levels were compared within each cancer group between the two time-points using the Wilcoxon Rank Sum test. RESULTS: At the first time-point in Group 1 (n = 46), median VEGF-A and D levels were measured at 5.2 (pg/ml) (range = 0-97) and 319 (range = 172-780) (pg/ml). For Group 2 (n = 34) VEGF-A level was 9.6 pg/ml (range = 0-78) and VEGF-D level was 377 pg/ml (range = 243-989) for the first measurement. Median time-period for the serial second specimen was 189 days in Group 1 and 84 days in Group 2. At the second time-point, in Group 1, VEGF-A levels were 0.0 pg/ml (P = 0.0002) while VEGF-D increased to 349 pg/ml (P = 0.002). For Group 2 patients at the second time-point, median VEGF-A was 0.0 pg/ml (P = 1.0) and VEGF-D was measured at 442 pg/ml (P = 0.008). CONCLUSIONS: Higher plasma VEGF-D than VEGF-A expression in advanced PCa stages suggests a greater role for VEGF-D dependent lymph angiogenesis in advanced stage PCa, which needs further evaluation.

High prevalence of tcdC deletion-carrying Clostridium difficile and lack of association with disease severity.

We assessed the prevalence of tcdC deletion-carrying Clostridium difficile using a stool polymerase chain reaction (PCR) assay that detects previously described 18- and 39-bp deletions (J. Clin. Microbiol. 2008;46:1996). We divided inpatients into 2 groups, those for whom the assay detected a deletion in tcdC and those for whom no deletion was detected. We compared risk factors (antibiotic use, hospitalization, nursing home stay, immunocompromise, age >65 years), complications (pseudomembranous colitis, toxic megacolon, colonic perforation, colectomy, and intensive care unit admission), duration of antibiotic treatment, and 30-day mortality between the groups. Forty-two of 141 patients had deletion-positive C. difficile. Prior nursing home stay and age >65 years were significantly more common in the deletion-positive group. Other risk factors, complications, antibiotic duration, and mortality did not differ significantly. Deletion-carrying C. difficile was commonly present but not associated with more severe disease and not markedly different in terms of risk factor profile. Severity of disease was relatively low, regardless of the presence or absence of a deletion.

Effect of telephoned notification of positive Clostridium difficile test results on the time to the ordering of antimicrobial therapy.

The time between electronic-medical-record reporting of a positive result of a test for Clostridium difficile toxin in stool and the ordering of antimicrobial therapy was compared during consecutive periods when results were not telephoned (n = 274) and when results were telephoned (n = 90) to the clinical service. The mean times to the ordering of antimicrobial therapy were 11.9 and 3.6 hours, respectively (P < .001).