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The COVID-19 pandemic has disproportionately impacted frail older adults, especially residents of long-term care (LTC) facilities. This has appropriately led to prioritization of frail older adults and LTC residents, and those who care for them, in the vaccination effort against COVID-19. Older adults have distinct immunological, clinical, and practical complexity, which can be understood through a lens of frailty. Even so, frailty has not been considered in studies of COVID-19 vaccines to date, leading to concerns that the vaccines have not been optimally tailored for and evaluated in this population even as vaccination programs are being implemented. This is an example of how vaccines are often not tested in Phase 1/2/3 clinical trials in the people most in need of protection. We argue that geriatricians, as frailty specialists, have much to contribute to the development, testing and implementation of COVID-19 vaccines in older adults. We discuss roles for geriatricians in ten stages of the vaccine development process, covering vaccine design, trial design, trial recruitment, establishment and interpretation of illness definitions, safety monitoring, consideration of relevant health measures such as frailty and function, analysis methods to account for frailty and differential vulnerability, contributions in regulatory and advisory roles, post-marketing surveillance, and program implementation and public health messaging. In presenting key recommendations pertinent to each stage, we hope to contribute to a dialogue on how to push the field of vaccinology to embrace the complexity of frailty. Making vaccines that can benefit frail older adults will benefit everyone in the fight against COVID-19., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/kVCbo9QA9O4

Background/objectives Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes. Design/setting Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods. Participants/intervention In the two parent studies, participants aged ≥50 years (ZOE-50 study) and ≥70 years (ZOE-70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo. Measurements In the current ZOE-Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety. Results Of 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre-frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50-59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). The RZV group demonstrated robust anti-gE antibody and gE-specific CD42+ responses, with mean concentrations remaining above pre-vaccination levels at least 3 years post-dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty. Conclusion The relatively nonrestrictive inclusion/exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre-frail older adults. RZV significantly reduced the risk of herpes zoster across all frailty subgroups.

Background Herpes zoster may significantly impact quality of life (QoL) in older adults. The recombinant zoster vaccine (RZV) is efficacious in adults aged ≥50 and older and is associated with increased reactogenicity compared to placebo. We report here on the impact of reactogenicity of the second RZV dose on the QoL and physical functioning (PF) of vaccine recipients, and summarize findings following both doses. Method In this single-arm study, 401 adults aged ≥50 and older were enrolled to receive two RZV doses 2 months apart. Change in mean Short Form Survey-36 (SF-36) PF and EuroQol-5 Dimension (EQ-5D) scores, reactogenicity, safety, productivity loss, and healthcare resource utilization were evaluated. Results In total, 391 (97.5%) participants received dose 2. Post-dose 2, the most common solicited local symptoms were injection site pain (75.1%), erythema (22.4%), and swelling (13.9%), and the most common systemic symptoms were fatigue (46.3%), headache (37.5%), and myalgia (32.9%). Grade 3 solicited (local and systemic) adverse events were reported by 61 (15.6%) participants and were associated with a transient clinically significant decrease in SF-36 PF score on Days 1–2 post-dose 2 that recovered by Day 3. Overall, no clinically important reduction in mean SF-36 PF scores was observed from baseline to post-dose 2 (mean change −0.4), and no quality-adjusted-life-year loss was recorded. Conclusions Overall, QoL and PF of RZV vaccinees were not affected by vaccine-related reactogenicity. A transient reduction was observed in the first 2 days after RZV vaccination in individuals with Grade 3 adverse events. No safety concerns were identified.

PURPOSE: Evaluate risk factors for cytomegalovirus (CMV) reactivation during the first year after kidney transplantation in the CMV seropositive older recipient. METHODS: Retrospective single-center study. RESULTS: Between 2011-2015, 91 patients ≥65 years received a kidney transplant; these were matched with 91 controls, aged 40-60. Risk of CMV reactivation in the CMV seropositive recipients was analyzed. Sixty-three older and 54 younger recipients were included; 50% had received CMV-directed prophylaxis. CMV reactivation was significantly more frequent in the older group (71.4% vs 44.4%, p=0.003) and occurred earlier (p=0.003). A multivariate model showed that only age was associated with CMV reactivation (OR 2.48, p=0.03). After excluding patients that received thymoglobulin, older age group remained the only risk factor of CMV reactivation (OR 3.81, p=0.014). Recurrent event analysis showed that the older cohort had an HR of 1.94 (p=0.01) of CMV viremia; there was significant episode-cohort interaction (p

Frail older adults are at increased risk of poor clinical outcomes. Frailty assessment is therefore important in clinical trials to understand the benefits and harms of interventions. However, consensus is lacking on how frailty should be assessed. We developed a prospectively specified index using a battery of formal tests and instruments and a retrospectively generated index using medical comorbidities and patient reported outcomes (PROs) within an adjuvanted recombinant zoster vaccine (RZV) trial (NCT02979639). For both frailty indices (FIs), a total deficit score was calculated as the accumulation of deficits and participants were categorized as non-frail, pre-frail and frail. We assessed (1) the feasibility and validity of both FIs; (2) the impact of RZV vaccine reactogenicity by frailty status on Short Form-36 [SF-36] physical functioning (PF) scores. Of 401 participants, aged ≥50 years, 236 (58.9%) were categorized non-frail, 143 (35.7%), pre-frail, and 22 (5.5%) frail using the prospective FI. Corresponding numbers for the retrospective FI were 192 (47.9%), 169 (42.1%) and 40 (10.0%), respectively. Strong concordance was observed between the frailty status assessments (P

Background Approaches for quantifying physical resilience in older adults have not been described. Methods We apply two conceptual approaches to defining physical resilience to existing longitudinal data sets in which outcomes are measured after an acute physical stressor. A “recovery phenotype” approach uses statistical methods to describe how quickly and completely a patient recovers. Statistical methods using a recovery phenotype approach can consider multiple outcomes simultaneously in a composite score (eg, factor analysis and principal components analysis) or identify groups of patients with similar recovery trajectories across multiple outcomes (eg, latent class profile analysis). An “expected recovery differential” approach quantifies how patients’ actual outcomes are compared to their predicted outcome based on a population-derived model and their individual clinical characteristics at the time of the stressor. Results Application of the approaches identified different participants as being the most or least physically resilient. In the viral respiratory cohort (n = 186) weighted kappa for agreement across resilience quartiles was 0.37 (0.27–0.47). The expected recovery differential approach identified a group with more comorbidities and lower baseline function as highly resilient. In the hip fracture cohort (n = 541), comparison of the expected recovery differentials across 10 outcome measures within individuals provided preliminary support for the hypothesis that there is a latent resilience trait at the whole-person level. Conclusions We posit that recovery phenotypes may be useful in clinical applications such as prediction models because they summarize the observed outcomes across multiple measures. Expected recovery differentials offer insight into mechanisms behind physical resilience not captured by age and other comorbidities.

PURPOSE: Infections are among the top three causes of death of older adults in the first year after kidney transplantation (KT). Our aim was to describe infectious complications among KT recipients aged ≥65 during the first 12 months post-transplant. METHODS: Single center retrospective cohort study. RESULTS: Ninety-one KTs had been performed in patients ≥ 65 years of age between 2011–2015. 92.3% of the patients developed at least one infection. Infectious episodes increased the risk of future infection by 10% (p=0.0018) with each infection portending a greater risk. At a patient level, viral (71.4%) and bacterial (70.2%) infections predominated. Urinary tract infections were the most frequent complication (30.3%), followed by cytomegalovirus infections (22.7%). Infections were the main reason for readmission. 7.7% of the patients developed rejection; and overall 3.3% lost their graft. Mortality at one year was 9.9%. CONCLUSIONS: Older KT recipients have a high incidence of infectious complications the first year after KT. Infections were the number one reason for readmission, and an infection episode predicted future infections for the individual patient. Despite these complications, the majority of older KT recipients were alive with a functioning graft at one-year.

Background Herpes zoster and its related complications are associated with significant medical burden, which negatively affects quality of life and daily functioning of the patients. The recently licensed recombinant zoster vaccine (RZV) offers high efficacy but is associated with local and systemic reactions. This study assessed the impact of RZV on the quality of life and daily functioning of participants and implications for caregivers. Methods Four hundred and one adults aged 50 years or older received single RZV doses at 0 and 2 months in this open-label, single-arm, multicenter study (NCT02979639). Change in mean SF-36 Physical Functioning score following first-dose administration, quality of life, reactogenicity, safety, productivity loss, and health care resource utilization was assessed. The current analysis was performed post-vaccine dose-1; safety follow-up will continue until 1 year post-dose-2. Results The most common solicited local symptoms were injection-site pain (77.5%), redness (23.0%), and swelling (13.3%); the most frequent solicited systemic reactions were fatigue (33.5%), headache (28.3%), and myalgia (26.8%). Grade 3 reactogenicity occurred in 9.5% of participants and was associated with a transient clinically important decrease in SF-36 Physical Functioning score (affecting activities such as walking, carrying groceries, climbing stairs) on Days 1 and 2 post-first vaccination. No clinically meaningful reductions in mean SF-36 Physical Functioning scale scores from pre- to post-RZV dose-1 were observed (mean +1.9 points, primary end point), and no overall quality-adjusted-life-year loss was recorded post-dose-1. Five participants reported lost workdays; caregiver workload was not increased. Conclusions Overall, the physical functioning and quality of life of older adults were not affected by a first RZV dose. The observed reactogenicity was consistent with previous studies.

Protection against zoster conferred by zoster vaccine live (ZVL; Zostavax) wanes over time. We compared varicella-zoster virus cell-mediated immunity (VZV-CMI) of adults ≥70 years who received a second dose of ZVL ≥10 years after the initial dose with de novo-immunized age-matched controls. Before and during the first year after vaccination, VZV-CMI was significantly higher in reimmunized compared with de novo vaccinees. At 3 years, VZV-CMI differences between groups decreased and only memory responses remained marginally higher in reimmunized participants. In conclusion, the increase in VZV-CMI generated by reimmunization with ZVL is at least equally persistent compared with de novo immunization.

Antibody responses, B cell subset distribution in blood and the blood transcriptome were analyzed in younger and aged human subjects before and after vaccination with the inactivated influenza vaccine. In the aged, but not the younger, individuals we saw a clear difference in antibody titers including those at baseline depending on the time of vaccination and sample collection. Differences in baseline titers in aged individuals treated in the morning or afternoon in turn affected responsiveness to the vaccine. In both younger and aged individuals, the time of sample collection also affected relative numbers of some of the B cell subsets in blood. A global gene expression analysis with whole blood samples from the aged showed small but statistically significant differences depending on the time of sample collection. Our data do not indicate that timing of vaccination affects immune responsiveness of the aged, but rather shows that in clinical influenza vaccine trials timing of collection of samples can have a major and potentially misleading influence on study outcome. In future vaccine trials, timing of vaccination and sample collection should be recorded carefully to allow for its use as a study covariant.

Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of the live attenuated zoster vaccine (ZVL) have a very-well-described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunological factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot assays and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak T helper 1 (VZV-Th1) responses to ZVL were independently predicted by prevaccination VZV-Th1 responses, regulatory T cells (Treg), and PD1-expressing immune checkpoint T cells (Tcheck) but not by the age of the vaccinee. Persistence of VZV-Th1 1 year after vaccination was independently predicted by the factors mentioned above, by peak VZV-Th1 responses to ZVL, and by the age of the vaccinee. We further demonstrated by ex vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of prevaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults. IMPORTANCE Vaccination is the most effective method to protect older adults against viral infections. However, the immunogenicity of viral vaccines in older adults is notoriously poor. The live attenuated zoster vaccine (ZVL) provides the best example of a gradual decrease of vaccine immunogenicity with every 10-year age increase above 50 years. Here we show that the abundance of regulatory T cells before vaccine administration to older adults has a significant inhibitory effect on immune responses to ZVL and, together with baseline immunity to varicella-zoster virus, explains the effect of age on the immunogenicity of ZVL. Moreover, in vitro blockade of regulatory T cell mechanisms of action with biologic modulators restores immune responses to varicella-zoster virus in vaccinees. Collectively, these observations suggest that immune modulators that block regulatory T cell activity may increase responses to viral attenuated vaccines in older adults.

// Raj Kurupati 1,* , Andrew Kossenkov 1,* , Larissa Haut 1 , Senthil Kannan 1,2 , Zhiquan Xiang 1 , Yan Li 1 , Susan Doyle 3 , Qin Liu 1 , Kenneth Schmader 3 , Louise Showe 1 and Hildegund Ertl 1 1 The Wistar Institute, Philadelphia, PA, USA 2 Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA 3 Development and Division of Geriatrics, GRECC, Durham VA Medical Center and Center for the Study of Aging and Human, Department of Medicine, Duke University Medical Center, Durham, NC, USA * These authors have contributed equally to this work Correspondence to: Hildegund Ertl, email: // Keywords : B cell responses, inactivated influenza vaccine, race, Immunology and Microbiology Section, Immune response, Immunity Received : June 17, 2016 Accepted : August 25, 2016 Published :August 30, 2016 Abstract We conducted a 5-year study analyzing antibody and B cell responses to the influenza A virus components of the inactivated influenza vaccine, trivalent (IIV3) or quadrivalent (IIV4) in younger (aged 35-45) and aged (≥65 years of age) Caucasian and African American individuals. Antibody titers to the two influenza A virus strains, distribution of circulating B cell subsets and the blood transcriptome were tested at baseline and after vaccination while expression of immunoregulatory markers on B cells were analyzed at baseline. African Americans mounted higher virus neutralizing and IgG antibody responses to the H1N1 component of IIV3 or 4 compared to Caucasians. African Americans had higher levels of circulating B cell subsets compared to Caucasians. Expression of two co-regulators, i.e., programmed death (PD)-1 and the B and T cell attenuator (BTLA) were differentially expressed in the two cohorts. Race-related differences were caused by samples from younger African Americans, while results obtained with samples of aged African Americans were similar to those of aged Caucasians. Gene expression profiling by Illumina arrays revealed highly significant differences in 1368 probes at baseline between Caucasians and African Americans although samples from both cohorts showed comparable changes in transcriptome following vaccination. Genes differently expressed between samples from African Americans and Caucasians regardless of age were enriched for myeloid genes, while the transcripts that differed in expression between younger African Americans and younger Caucasians were enriched for those specific for B-cells.

Antibody responses to vaccinations or infections decline upon aging. In this study we tested if metabolic changes in B cells may contribute to attenuation of responses to influenza vaccination in aged humans. Our data show that aging affects mitochondrial functions in B cells leading to increases in mitochondrial reactive oxygen species (MROS) and mitochondrial mass (MM) in some aged B cell subsets and decreases in expression levels of Sirtuin 1 (SIRT1), Forkhead box protein (FOX)O1 and carnitine palmitoyltransferase 1 (CPT-1). Seahorse analyses showed minor defects in glycolysis in the aged B cells after activation but a strong reduction in oxidative phosphorylation. The analyses of the transcriptome revealed further pronounced defects in one-carbon metabolism, a pathway that is essential for amino acid and nucleotide metabolism. Overall our data support the notion that the declining ability of aged B cells to increase their metabolism following activation contributes to the weakened antibody responses of the elderly.

Improving the quality of medication use and medication safety is an important priority for prescribers who care for older adults. The objective of this article was to identify key articles from 2018 that address these issues. In addition, we selected four of these articles to annotate, critique, and discuss their broader implications for clinical practice. The first study highlights a cluster-randomized trial that utilized a pharmacist-led education-based intervention delivered to both patients and physicians to deprescribe four types of inappropriate medications (sedative-hypnotics, first-generation antihistamines, selective nonsteroidal anti-inflammatory drugs, and glyburide). The second study, a nested case-control study using data from within the UK Clinical Practice Research Datalink, examined the association between anticholinergic exposure, overall and by anticholinergic medication class, and dementia risk in 40 770 older adults. The third study, a longitudinal cohort study of 1028 Swedish older adults, examined the association between antihypertensive medications and incident dementia. The last study was a randomized, double-blind, placebo-controlled trial that investigated the effect of daily low-dose aspirin (100 mg) for primary prevention on cardiovascular events and major hemorrhage in 19 144 community-dwelling older adults. Collectively, this current article provides insight into the pertinent topics of medication use quality and safety in older adults and helps raise awareness about optimal prescribing in older adults. J Am Geriatr Soc 67:2458-2462, 2019.

OBJECTIVES To identify the top priority areas for research to optimize pharmacotherapy in older adults with cardiovascular disease (CVD). DESIGN Consensus meeting. SETTING Multidisciplinary workshop supported by the National Institute on Aging, the American College of Cardiology, and the American Geriatrics Society, February 6–7, 2017. PARTICIPANTS Leaders in the Cardiology and Geriatrics communities, (officers in professional societies, journal editors, clinical trialists, Division chiefs), representatives from the NIA; National Heart, Lung, and Blood Institute; Food and Drug Administration; Centers for Medicare and Medicaid Services, Alliance for Academic Internal Medicine, Patient‐Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, pharmaceutical industry, and trainees and early career faculty with interests in geriatric cardiology. MEASUREMENTS Summary of workshop proceedings and recommendations. RESULTS To better align older adults’ healthcare preferences with their care, research is needed to improve skills in patient engagement and communication. Similarly, to coordinate and meet the needs of older adults with multiple comorbidities encountering multiple healthcare providers and systems, systems and disciplines must be integrated. The lack of data from efficacy trials of CVD medications relevant to the majority of older adults creates uncertainty in determining the risks and benefits of many CVD therapies; thus, developing evidence‐based guidelines for older adults with CVD is a top research priority. Polypharmacy and medication nonadherence lead to poor outcomes in older people, making research on appropriate prescribing and deprescribing to reduce polypharmacy and methods to improve adherence to beneficial therapies a priority. CONCLUSION The needs and circumstances of older adults with CVD differ from those that the current medical system has been designed to meet. Optimizing pharmacotherapy in older adults will require new data from traditional and pragmatic research to determine optimal CVD therapy, reduce polypharmacy, increase adherence, and meet person‐centered goals. Better integration of the multiple systems and disciplines involved in the care of older adults will be essential to implement and disseminate best practices. J Am Geriatr Soc 67:371–380, 2019.

Introduction Compared with younger populations, adults 65 years and older are more likely to suffer infection-related morbidity and mortality, experience antibiotic-related adverse events, and acquire multidrug-resistant organisms. We developed a series of case-based discussions that stressed antibiotic stewardship while addressing management of common infections in older adults. Methods Five 1-hour case-based discussions address recognition, diagnosis, and management of infections common in older adults, including those living in long-term care settings: urinary tract infections, upper respiratory tract infections, lower respiratory tract infections, skin and soft tissue infections, and Clostridium difficile infection. The education was implemented at the skilled nursing centers at 15 Veterans Affairs medical centers. Participants from an array of disciplines completed an educational evaluation for each session as well as a pre- and postcourse knowledge assessment. Results The number of respondents to the educational evaluation administered following each session ranged from 68 to 108. Learners agreed that each session met its learning objectives (4.80–4.89 on a 5-point Likert scale, 5 = strongly agree) and that they were likely to make changes (2.50–2.89 on a 3-point scale, 3 = highly likely to make changes). The average score on the five-question knowledge assessment increased from 3.6 (72%) to 3.9 (78%, p = .06). Discussion By stressing recognition of atypical signs and symptoms of infection in older adults, diagnostic tests, and antibiotic stewardship, this series of five case-based discussions enhanced clinical training of learners from several disciplines.

The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing.

Background An explicit goal of Patient Aligned Care Teams (PACTs) within the Veterans Health Administration is to promote continuity of care in primary care clinics and thereby reduce Emergency Department (ED) utilization; however, there has been little research to guide PACTs on how to accomplish this. Objectives The overall goal of this study is to examine the impact of a primary care-based nurse telephone support program [DISPO ED] on Veterans treated and released from the ED who are at high risk for repeat visits. Methods This study is a two group randomized, controlled trial to evaluate DISPO ED for Veterans treated and released from the ED who are at high risk for repeat visits. We define high risk as those who have had an ED visit or hospitalization during the 6 month period before the index ED visit and have ≥ 2 chronic conditions. Veterans are randomized to nurse telephone support or usual care. The primary outcome is repeat ED use within 30 days; secondary outcomes are patient satisfaction with care and total costs. Discussion The results of this randomized, controlled trial with an Effectiveness–Implementation Type I Hybrid design will be directly relevant to the care of more than 500,000 high risk patients seen in Veterans' Affairs Medical Center (VAMC) EDs annually. Results will also be informative to health systems outside VA aiming to reduce ED use through accountable care organizations.

Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing Ab titers, is increased in the elderly compared with young adults. The T follicular helper cell (Tfh) subset of CD4 T cells provides B cell help in germinal centers and is necessary for class-switched Ab responses. Previous studies suggested a role for circulating Tfh cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults in whom weak vaccine responses are often observed. In this study, we studied cTfh expressing CXCR5 and programmed death-1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and had greater expression of ICOS compared with young adults. At 7 d after inactivated influenza vaccination, cTfh correlated with influenza vaccine–specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh that correlated with reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging.

Objectives To quantify the effect of nosocomial bloodstream infection (BSI) on older adults, including mortality, length of stay (LOS), and costs attributed to BSI. Design Retrospective cohort study. Setting Eight acute care hospitals (7 community hospitals and 1 tertiary university-affiliated facility) belonging to the Duke Infection Control Outreach Network (DICON) from the states of North Carolina and Virginia. Participants Elderly patients over 65 years of age. Measurements A multistate, multicenter, matched, retrospective cohort study was conducted from January 1994 through June 2002 in eight hospitals from the Southern-Central United States. Patients aged >65 years with nosocomial BSI were enrolled. Controls without bloodstream infection were matched to cases. Outcomes during the 90-day period following hospital discharge were evaluated to determine the association between BSI and mortality, hospital costs, and LOS. Results Eight-hundred thirty cases and 830 matched controls were identified, all with a mean age of 74.4 years. Among cases, 81% of BSIs were central line-associated and Staphylococcus aureus was the most common pathogen accounting for 34.6% of infections (2/3 were methicillin resistant). The mortality rate of cases was 49.4%, compared to 33.2% for controls (OR = 2.1, P

The live attenuated herpes zoster (HZ) vaccine (zoster vaccine [ZV]; ZostavaxTM; Merck & Co., Inc.) was recommended by the Advisory Committee on Immunization Practices in the United States in 2008 for immunocompetent individuals aged ≥60 years, based on a large randomized, placebo-controlled trial, the Shingles Prevention Study (SPS) [1, 2]. There is strong clinical evidence that varicella-zoster virus (VZV)–specific cell-mediated immunity (VZV CMI) is both necessary and sufficient to prevent HZ and that ZV prevents HZ because it stimulates VZV CMI [3–6]. It is believed that there is a causal inverse relationship between the loss of VZV CMI that occurs with aging and the age-related increase in HZ. In contrast, VZV-specific immunoglobulin G antibody (VZV antibody) does not decline with age [3, 7]. Nevertheless, the SPS demonstrated that a measure of VZV antibody, in addition to 2 measures of VZV CMI, correlated with protection against HZ, although no quantitative measure of any of these responses reliably predicted the extent of protection [8]. A subsequent efficacy trial of ZV in 22 439 subjects 50–59 years old demonstrated an efficacy of 69.8% for preventing HZ [9]. Ten percent of subjects were randomly assigned to an immunology substudy/subcohort that measured VZV antibody response to ZV. The substudy objectives were to determine if ZV in 50–59-year-olds is immunogenic (as evaluated by glycoprotein enzyme-linked immunosorbent assay [gpELISA]) and to assess the association between antibody response at week 6 after vaccination and the risk of HZ.

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was

Antibody and B cell responses to influenza A viruses were measured over a period of 2 months in 30 aged and 15 middle-aged individuals following vaccination with the 2011/12 trivalent inactivated influenza vaccine by micro-neutralization assays, ELISAs, ELISpot assays and cell surface staining with lineage-defining antibodies followed by multicolor flow cytometry. Both cohorts developed comparable antibody responses to the H3N2 virus of the vaccine while responses to the H1N1 virus were compromised in the aged. ELISpot assays of peripheral blood mononuclear cells (PBMCs) gave comparable results for the two cohorts. Analysis by flow cytometry upon staining of CD19+IgD-CD20- PBMCs with antibodies to CD27 and CD38 showed markedly reduced increases of such cells following vaccination in the aged. Additional analysis of cells from a subset of 10 younger and 10 aged individuals indicated that in the aged a portion of IgG producing cells lose expression of CD27 and reduce expression of CD38.

Increased T-bet levels and senescence in CD8 T cells from aged individuals as possible mechanisms for decreased influenza-specific functionality. Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.

This manuscript describes the functional status trajectory of older (age 65 or older) and younger (age 18–64) adults after Lung Transplantation (LT). After the implementation of the Lung Allocation Score (LAS) in 2005, older adults became the fastest growing subgroup of recipients. Yet the impact of LT on physical function, a main determinant of quality of life in older adults, is unknown. We conducted a retrospective cohort study using United Network for Organ Sharing data on 4805 adults who received a LT during 2005–2009. We divided them into older (≥65, n=774) and younger (18–64, n=4031) cohorts. Functional status was measured by Karnofsky Performance Score (KPS). Mixed models estimated the impact of age group on the rate of functional decline starting at one-year post-transplantation. We controlled for KPS at transplantation, gender, race, diagnosis, LAS and LT type. Age group was not associated with different rates of decline in KPS over time. On average, recipients who were older, received a single LT, or had a low KPS at transplantation had worse functional status post-transplantation when compared to their counterparts, but rarely reached disability at 48-months. Overall, LT had a positive and durable effect on physical function for both older and younger recipients.

Background Study goals were to assess older veterans' understanding of their emergency department (ED) discharge information and to determine the association between understanding discharge information and patient assessment of overall quality of care. Methods Telephone interviews were conducted with 305 patients aged 65 or older (or their proxies) within 48 h of discharge from a Veterans Affairs Medical Center ED. Patients were asked about their perceived understanding (at the time of ED discharge) of information about their ED diagnosis, expected course of illness, contingency plan (ie, return precautions, who to call if it got worse, potential medication side effects) and follow-up care. Overall quality of ED care was rated on a four-point scale of poor, fair, good or excellent. Results Patients or their proxies reported not understanding information about their ED diagnosis (21%), expected course of illness (50%), contingency plan (43%), and how soon they needed to follow-up with their primary care provider (25%). In models adjusted for age and race, a positive association was observed between perceived understanding of the cause of the problem (OR 2.3; 95% CI 1.3 to 4.0), expected duration of symptoms (OR 1.6; 95% CI 1.0 to 2.5) and the contingency plan (OR 2.2; CI 1.3 to 3.4), and rating overall ED care as excellent. Conclusions Older veterans may not understand key items of information at the time ED discharge, and this may have an impact on how they view the quality of ED care. Strategies are needed to improve communication of ED discharge information to older veterans and their families.

Background. Herpes zoster (HZ) adversely affects individuals aged 50‐59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50‐59 years. Methods. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50‐59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for $1 year (mean, 1.3 years) postvaccination until accrual of $96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. Results. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1‐80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. Conclusions. In subjects aged 50‐59 years, the ZV significantly reduced the incidence of HZ and was well tolerated.

Infections threaten successful outcomes after kidney transplantation. Our aim was to determine if the number, types of infections and the risk factors for common infections differed between older compared to younger kidney transplant (KT) recipients in the first year after surgery. We performed a single-center retrospective cohort study. Between 2011 and 2015, 91 KTs were performed in patients ≥65 years of age; these were matched 1:1 (by year of transplantation, sex and race) to controls aged 40-60 years. Over 90% of both groups had an infectious complication. Urinary tract infections (UTIs) and cytomegalovirus (CMV) viremia were significantly more frequent in older recipients. Older adults had more late onset UTIs, including after stent removal. CMV viremia was more frequent in older adults in the 1-6 months post-transplant period. Due to our center-specific protocol utilizing pre-emptive monitoring in the CMV recipient-seropositive population, the higher CMV incidence in the aged recipient was driven by this subpopulation of older adults. No difference in pneumonias or bloodstream infections were found, nor in surgical complications, rejection or graft loss. Mortality was higher at 1-year post-transplant in the older recipients (9.9% vs 1.1%; P = 0.018). Prophylactic and immunosuppressive strategies may need to be altered for older KT recipients.

To describe older patients' understanding of emergency department (ED) discharge information and to explore the relationship between understanding of ED discharge information and adverse outcomes.Telephone interviews were conducted with patients 65 years or older (or their proxies) within 72 hours of discharge from an academic medical center ED. We assessed 4 areas of discharge information: ED diagnosis, expected course of illness, self-care instructions, and return precautions. Adverse events were defined as repeat ED visits and hospitalizations or deaths within 90 days of ED discharge. Reverse Kaplan-Meier curves were constructed to illustrate cumulative event probabilities according to patient understanding of discharge information (differences examined with log-rank tests).Of 92 respondents (mean patient age, 75.1; SD, 7.4; 59.8% female subjects), patients or proxies reported not understanding discharge information about diagnosis (20.7%), self-care instructions (16.3%), expected course of illness (63%), and return precautions (55.7%). Within 90 days of ED discharge, 42.3% of patients had returned to the ED, 30.4% were hospitalized, and 4.3% had died. There was little difference in cumulative event probabilities according to whether patients understood self-care instructions or return precautions. Adverse event probabilities were higher among patients who did not understand their ED diagnosis (P = 0.33) and those who did not understand expected course of illness (P = 0.12), although these did not achieve statistical significance.A substantial number of older patients, or proxies, may not understand ED discharge information, and this could have an effect on patient outcomes. Strategies are needed to improve communication of ED discharge information to older patients and their families.

Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late. The incidence of acute kidney injury is rising and increases with advancing age, yet clinical studies have been slow to address geriatric issues or the heterogeneity in etiologies, outcomes, or patient preferences among the elderly. Here we examine some of the current literature, identify knowledge gaps, and suggest potential research questions regarding acute kidney injury in older adults. Answering these questions will facilitate the integration of geriatric issues into future mechanistic and clinical studies that affect management and care of acute kidney injury.

Currently, an estimated 38 million individuals 65 years or older live in the United States, and more than 11 million of these individuals are 80 years or older. Older people are at high risk of neuropathic pain because many diseases that cause neuropathic pain increase in incidence with age. Depending on their underlying health, older adults with neuropathic pain may have to cope with multiple coexisting diseases, polypharmacy, and impaired functional ability. The objective of this article is to review how aging and frailty affect the treatment of older adults with neuropathic pain. Specific topics reviewed include the complexity of treatment decisions in older patients due to aged heterogeneity, multimorbidity, and polypharmacy; selection of treatment in an effort to maximize patients' functional abilities in addition to relieving their pain; more careful dosing (usually lower) and monitoring of pharmacotherapy relative to younger patients due to age-related changes in pharmacokinetics and pharmacodynamics; and underrepresentation of older adults in clinical trials of neuropathic pain treatments, which further compromises physicians' ability to make informed treatment decisions.

Background: Medication underutilization, or the omission of a potentially beneficial medication indicated for disease management, is common among older adults but poorly understood. Objectives: The aims of this work were to assess the prevalence of medication underuse and to determine whether polypharmacy or comorbidity was associated with medication underuse among physically frail older veterans transitioning from the hospital to the community. Methods: This was a cross-sectional analysis of patients who were discharged from 11 US veterans' hospitals to outpatient care, based on data from the Geriatric Evaluation and Management Drug Study, a substudy of the Veterans Affairs Cooperative Study of geriatric evaluation and management. Patients were enrolled between August 31, 1995, and January 31, 1999. To qualify for the study, patients had to be aged ≥65 years, hospitalized in a medical or surgical ward for >48 hours, and meet ≥2 of the following criteria: moderate functional disability; recent cerebrovascular accident with residual neurological deficit; history of ≥1 fall in the previous 3 months; documented difficulty with walking (ie, requiring personal assistance or equipment), not including preadmission use of a wheelchair with ability to transfer to and from chair independently; malnutrition (admission serum albumin of 3.5 g/dL

Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health-related quality of life, there have been no randomized clinical trials of oral medications specifically for its ongoing treatment. A randomized clinical trial was conducted in which 87 subjects >or=50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24h >or=3 on a 0-10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled-release (CR) oxycodone, gabapentin, or placebo. Subjects were evaluated for adverse effects of treatment, acute pain, and health-related quality of life. The results showed that CR-oxycodone and gabapentin were generally safe and were associated with adverse events that reflect well-known effects of these medications. Discontinuing participation in the trial, primarily associated with constipation, occurred more frequently in subjects randomized to CR-oxycodone (27.6%) compared with placebo (6.9%). Treatment with CR-oxycodone reduced the mean worst pain over days 1-8 (p=0.01) and days 1-14 (p=0.02) relative to placebo but not throughout the entire 28-day treatment period as pain resolved in most subjects. Gabapentin did not provide significantly greater pain relief than placebo, although the data for the first week were consistent with a modest benefit. By demonstrating that CR-oxycodone is safe, generally adequately tolerated, and appears to have efficacy for relieving acute pain, the results of this clinical trial provide a foundation for evidence-based treatment for acute pain in herpes zoster.

Background: Older adults who are discharged from the emergency department (ED) may be at risk for subsequent adverse outcomes; however, this has not been fully investigated in national, population-based samples. The goal of this study was to determine the frequency and predictors of adverse outcomes among older adults discharged from the ED. Design: Secondary analysis of data from the Medicare Current Beneficiary Survey. Subjects: A total of 1851 community-dwelling, Medicare fee-for-service enrollees, ≥65 years old who were discharged from the ED between January 2000 and September 2002. Measures: The primary dependent variable was time to first adverse outcome defined as any repeat outpatient ED visit, hospital admission, nursing home admission or death within 90 days of the index ED visit. Results: Six hundred twenty-three of 1851 subjects (32.9%) discharged from the ED experienced an adverse outcome within 90 days of the index visit; 17.2% returned to the ED but were not admitted, 18.3% were hospitalized, 2.6% were admitted to a nursing home, and 4.1% died. Patients who were older [hazard ratios (HR), 1.01; confidence interval (CI), 1.00–1.02], with more chronic health conditions (HR, 1.12; CI, 1.07–1.19), Medicaid insurance (HR, 1.42; CI, 1.11–1.82), and recent ED (HR, 1.46; CI, 1.17–1.82) or hospital use (HR, 1.80; CI, 1.50–2.17) were at particularly high risk. Conclusions: A substantial proportion of older Medicare beneficiaries in this study experienced an adverse outcome after ED discharge. Further study is needed to determine whether simple prediction tools based on these identified risk factors may be useful in predicting adverse outcomes in this vulnerable population.

Objective The goals of this study were to (1) determine whether level of social support and living situation predicted emergency department (ED) use among older adults and (2) identify correlates of ED visits according to whether the patient was admitted to the hospital. Methods Secondary analysis of a longitudinal, prospective study was conducted. Results In adjusted analyses, subjects who lived alone were 60% more likely to visit the ED than those who lived solely with their spouse. Neither type nor level of social support as measured by the Duke Social Support Index predicted ED use. Indicators of poor physical health (prior hospitalization, poorer self-rated health, and functional disability) were predictors of ED visits that resulted in hospitalization; however, these were not significantly associated with outpatient ED visits. Discussion Older adults who live alone are more likely to visit the ED. Additional study is needed to understand the determinants of outpatient ED visits.

An Emergency Department (ED) visit represents a time of significant risk for an older adult; however, little is known about adverse outcomes after an ED visit in the VA system.1) To describe the frequency and type of adverse health outcomes among older veterans discharged from the ED, and 2) To determine risk factors associated with adverse outcomes.Retrospective, cohort study at an academically affiliated VA medical center.A total of 942 veteransor = 65 years old discharged from the ED.Primary dependent variable was adverse outcome, defined as a repeat VA ED visit, hospitalization, and/or death within 90 days. Overall, 320 (34.0%) patients experienced an adverse outcome: 245 (26%) returned to the VA ED but were not admitted, 125 (13.3%) were hospitalized, and 23 (2.4%) died. In adjusted analyses, higher score on the Charlson Comorbidity Index (hazard ratio [HR] 1.11; 95% CI 1.03, 1.21), ED visit within the previous 6 months (HR 1.64; 95% CI 1.30, 2.06), hospitalization within the previous 6 months (HR 1.70, 95% CI 1.30, 2.22), and triage to the emergency unit (compared to urgent care clinic) (HR 1.76, 95% CI 1.32, 2.36) were independently associated with higher risk of adverse outcomes.More than 1 in 3 older veterans discharged from the ED experienced a significant adverse outcome within 90 days of ED discharge. Identifying veterans at greatest risk for adverse outcomes after ED discharge can inform the design and targeting of interventions to reduce morbidity and costs in this group.

Objectives To describe the interference of herpes zoster (HZ) pain and discomfort with activities of daily living (ADLs) and health-related quality of life (HRQL) during the acute rash phase, and to quantify the relationship between acute HZ pain and discomfort and impaired ADLs and HRQL in older persons. Methods Prospective, observational study of 160 HZ outpatients age > or =60 at 4 US study sites who completed the Zoster Brief Pain Inventory (ZBPI), Zoster Impact Questionnaire (ZIQ), McGill Pain Questionnaire, EuroQol, and SF-12 questionnaires on a predetermined schedule. Patients rated interference on a 0 to 10 scale for ADL items in the ZBPI and the ZIQ. Interference scores were averaged to create summary measures for the ZBPI items (ZBPI ADLI) and ZIQ items (ZIQ ADLI). A composite pain score was used in mixed-effects models analyses of the association between pain and discomfort and ADLI and HRQL measures during the first 35 days after HZ rash onset. Results HZ pain interfered with all ADLs but interference was greatest for enjoyment of life, sleep, general activity, leisure activities, getting out of the house, and shopping. For every 1.0 point increase in pain and discomfort intensity, there was a 0.69 and 0.53 point increase in ZBPI and ZIQ interference, respectively, and a 2.81 point, 1.57 point, and 1.95 point decrease in EuroQol, SF-12 physical, and SF-12 mental scales, respectively. Discussion Acute zoster pain and discomfort has a significant negative impact on functional status and HRQL in older adults. The magnitude of interference increases with increasing pain and discomfort intensity.

We tested antibody responses to the trivalent inactivated influenza vaccine (TIV) in 34 aged individuals (>65 yrs) during the 2012/13 vaccination seasons. Nearly all had been vaccinated the previous year although the time interval between the two vaccine doses differed. One subgroup was re-vaccinated in 2012/13 within 6-9 months of their 2011/12 vaccination, the other received the two doses of vaccine in the typical ~12 month interval. Unexpectedly the sub-cohort with early revaccination exhibited significantly increased response rates and antibody titers to TIV compared to their normally re-vaccinated aged counter parts. Microarray analyses of gene expression in whole blood RNA taken at the day of the 2012/13 re-vaccination revealed statistically significant differences in expression of 754 genes between the individuals with early re-vaccination compared to subjects vaccinated in a normal 12 month interval. These observations suggest that TIV has long-lasting effects on the immune system affecting B cell responses as well as the transcriptome of peripheral blood mononuclear cells and this residual effect may augment vaccination response in patients where the effect of the previous vaccination has not yet diminished.

Background Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). Methods Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. Results Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. Conclusions These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. Clinical trials registration NCT01245751.

// Senthil Kannan 1,2 , Raj K. Kurupati 2 , Susan A. Doyle 3 , Gordon J. Freeman 4 , Kenneth E. Schmader 3 and Hildegund C.J. Ertl 2 1 Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA 2 The Wistar Institute, Philadelphia, PA, USA 3 GRECC, Durham VA Medical Center and Center for the Study of Aging and Human, Development and Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA 4 Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Correspondence to: Hildegund C.J. Ertl, email: // Keywords : BTLA, aging, HSV, immunosenescence, influenza Received : June 03, 2015 Accepted : June 11, 2015 Published : June 21, 2015 Abstract Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shifting the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year.

Although therapeutic failure may be a common cause of drug-related morbidity in older adults, few studies have focused on this problem. The study objective was to determine the frequency and types of, and the factors associated with, therapeutic failure leading to hospitalisation in frail, elderly patients, using a new instrument named the Therapeutic Failure Questionnaire (TFQ).The sample included 106 frail, hospitalised elderly patients enrolled in a 1-year-long health service intervention trial at 11 Veterans Affairs Medical Centres. The TFQ was developed by a team of clinical geriatricians and tested for reliability by two clinical pharmacists and a geriatrician on a sample of 32 patients. To establish validity, a geriatrician retrospectively reviewed the computerised medication records and clinical charts for these patients and applied the TFQ to determine probable therapeutic failures at the time of hospital admission.Inter- and intra-rater reliability for the TFQ were very good (kappa = 0.82 for both). Overall, 11% of patients had one or more probable therapeutic failures (TFQ scores between 4 and 7) leading to hospitalisation. Cardiopulmonary disease was a common 'indicator' of therapeutic failure and was often the result of non-adherence. The only factor associated with therapeutic failure occurrence was severe chronic kidney disease (crude odds ratio 5.87; 95% CI 1.20, 28.69; p = 0.01).The TFQ was able to identify several cases of probable therapeutic failure leading to hospitalisation in frail, elderly patients. Non-adherence to effective therapies for chronic serious cardiopulmonary disease was a common cause of therapeutic failure and represents a target for interventions to reduce hospitalisation. Further research on the occurrence, risk factors for and types of therapeutic failure is needed in a larger cohort of older non-veterans.

BACKGROUND: Drugs can improve quality of life for many older people, but they may cause adverse health outcomes (eg, drug—disease interactions) if used inappropriately. OBJECTIVE: To determine the prevalence of potential drug—disease interactions as defined by explicit criteria and examine associations between sociodemographic and health status variables and potential drug—disease interactions. METHODS: The study design was cross-sectional. We evaluated 397 frail elderly inpatients from the Geriatric Evaluation and Management trial conducted at 11 Veterans Affairs Medical Centers. Drug—disease interactions were defined using explicit criteria from consensus expert panels of geriatricians from the US and Canada. RESULTS: Overall, 159 (40.1%) patients had one or more potential drug—disease interaction. The most common potential interactions were calcium-channel blockers and heart failure (12.3%) and β-blockers and diabetes (6.8%). Multivariable logistic regression analyses revealed that age ⩾75 years (adjusted OR 2.43; 95% CI 1.52 to 3.88), being married (adjusted OR 1.77; 95% CI 1.11 to 2.82), comorbidity index defined by Charlson method (adjusted OR 1.19; 95% CI 1.05 to 1.34), and use of multiple prescription drugs (5–8: adjusted OR 4.17; 95% CI 1.96 to 8.88, ⩾9: adjusted OR 9.22; 95% CI 4.26 to 19.95), were significantly (p < 0.05) associated with having one or more potential drug—disease interaction. CONCLUSIONS: Potential drug—disease interactions are common in hospitalized elderly patients and are related to specific sociodemographic and health status factors. Further research is needed to examine the relationship between health outcomes and drug—disease interactions.

Surgical site infections (SSIs) account for 11% of nosocomial infections among older patients. This report reviews the available data and presents medical and surgical perspectives on the epidemiology, outcomes, and prevention of SSI in the elderly population. The risk for SSI does not seem to increase after the age of 65 years. Several risk factors for SSI are similar among elderly patients and younger patients, but financial factors and factors related to health services may differ between the groups. The clinical presentation of infection and the pathogens that cause infection are similar among elderly patients and younger patients. However, the mortality rate, the duration of hospitalization, and the costs associated with hospital care are greater for elderly patients with SSI than for younger patients with SSI. Several modalities for SSI prevention have been well studied in the general surgical population but have not been specifically evaluated in the elderly surgical population. Insights and opinions pertaining to modalities for SSI prevention in the elderly population and areas of import for future research are discussed.

Objectives:To examine the impact of surgical-site infection (SSI) due toStaphylococcus aureuson mortality, duration of hospitalization, and hospital charges among elderly surgical patients and the impact of older age on these outcomes by comparing older and younger patients withS. aureusSSI.Design:A nested cohort study.Setting:A 750-bed, tertiary-care hospital and a 350-bed community hospital.Patients:Ninety-six elderly patients (70 years and older) withS. aureusSSI were compared with 2 reference groups: 59 uninfected elderly patients and 131 younger patients withS. aureusSSI.Results:Compared with uninfected elderly patients, elderly patients withS. aureusSSI were at risk for increased mortality (odds ratio [OR], 5.4; 95% confidence interval [CI95], 1.5-20.1), postoperative hospital-days (2.5-fold increase; CI95, 2.0-3.1), and hospital charges (2.0-fold increase; CI95, 1.7-2.4; $41,117 mean attributable charges per SSI). Compared with younger patients withS. aureusSSI, elderly patients had increased mortality (adjusted OR, 2.9; CI95, 1.1-7.6), hospital-days (9 vs 13 days;P= .001), and median hospital charges ($45,767 vs $85,648;P< .001).Conclusions:Among elderly surgical patients,S. aureusSSI was independently associated with increased mortality, hospital-days, and cost. In addition, being at least 70 years old was a predictor of death in patients withS. aureusSSI.

Background: The role of oxidative stress in the pathogenesis of diseases such as macular degeneration, certain types of cancer, and Alzheimer's disease has received much attention. Thus, there is considerable interest in the potential contribution of antioxidants to the prevention of these diseases. Objective: The objective of this study was to determine whether use of supplemental antioxidants (vitamins A, C, or E, plus selenium or zinc) was associated with a reduced risk of development of cognitive impairment or cognitive decline in a representative sample of the community-dwelling elderly. Methods: The sample consisted of 2082 nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly who were not cognitively impaired at the 1989–1990 interview (baseline for the present analysis). Medication use was determined during in-home interviews. Cognitive function was assessed 3 and 7 years from baseline in terms of incident cognitive impairment, as measured on the Short Portable Mental Status Questionnaire (SPMSQ) using specific cut points (number of errors) based on race and education, and cognitive decline, defined as an increase of ≥ 2 errors on the SPMSQ. Multivariate analyses were performed using weighted data adjusted for sampling design and controlled for sociodemographic characteristics, health-related behaviors, and healt status. Results: At baseline, 224 (10.8%) subjects were currently taking a supplement containing an antioxidant. During the follow-up period, 24.0% of subjects developed cognitive impairment and 34.5% experienced cognitive decline. Current antioxidant users had a 34.0% lower risk of developing cognitive impairment compared with non-antioxidant users (adjusted relative risk [RR], 0.66; 95% CI, 0.44–1.00) and a 29.0% lower risk of experiencing cognitive decline (adjusted RR, 0.71; 95% CI, 0.49–1.01). Conclusion: The results of this analysis suggest a possible beneficial effect of antioxidant use in terms of reducing cognitive decline among the community-dwelling elderly.

Objectives To describe the prevalence of and factors associated with drug–disease interactions (DDIs) in older nursing home residents according to the American Geriatrics Society 2012 Beers Criteria. Design Cross-sectional. Setting Fifteen Veterans Affairs Community Living Centers. Participants Individuals aged 65 and older with a diagnosis of dementia or cognitive impairment, a history of falls or hip fracture, heart failure (HF), a history of peptic ulcer disease (PUD), or Stage IV or V chronic kidney disease (CKD). Measurements Medications that could exacerbate the above conditions (DDIs). Results Three hundred sixty-one of 696 (51.9%) eligible residents had one or more DDIs. None involved residents with a history of PUD, one involved a resident with CKD, and four occurred in residents with HF. Of 540 residents with dementia or cognitive impairment, 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). Of 267 with a history of falls or hip fracture, 67.8% received an interacting medication, with selective serotonin reuptake inhibitors (33.1%), antipsychotics (30.7%), and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in dementia or cognitive impairment and falls or fractures included age 85 and older (adjusted odds ratio (aOR) = 0.38, 95% confidence interval (CI) = 0.24–0.60 and aOR = 0.48, 95% CI = 0.24–0.96, respectively), taking five to eight medications (aOR = 2.06, 95% CI = 1.02–4.16 and aOR = 4.76, 95% CI = 1.68–13.5, respectively), taking nine or more medications (aOR = 1.99, 95% CI = 1.03–3.85 and aOR = 3.68, 95% CI = 1.41–9.61, respectively), and being a long-stay resident (aOR = 1.80, 95% CI = 1.04–3.12 and aOR = 2.35, 95% CI = 1.12–4.91, respectively). Conclusion DDIs were common in older nursing home residents with dementia or cognitive impairment or a history of falls or fractures.

Reduced cell-mediated immunity (CMI) to varicella zoster virus (VZV) is associated with an increase in the risk and severity of herpes zoster (HZ) and its debilitating complications, including postherpetic neuralgia (PHN). This is true whether the reduction in VZV CMI is due to the age-related decline in CMI observed in normal older adults, or to immunosuppression caused by certain diseases or their treatments. Zoster vaccines containing the Oka strain of live attenuated VZV have proven to be safe and effective inolderadults, but currentrecommendations preclude their use in immunocompromised persons. In this issue of Clinical Infectious Diseases, Tseng et al [1] report that zoster vaccine, administered to adults ≥60 years of age, continued to protect against HZ when recipients subsequently underwent cancer chemotherapy. These findings underline the importance of administering zoster vaccine to immunocompetent older adults as currently recommended [2], and doing so as early as possible. In addition, the results of these and similar studies suggest that it may be time to review the current policy of excluding all immunocompromised persons from receiving zoster vaccine. The study by Tseng et al [1] was conducted among members of Kaiser Permanente Southern California (KPSC), an integrated healthcare system that pro

Herpes zoster (HZ) strikes millions of older adults annually worldwide and disables a substantial number of them via postherpetic neuralgia (PHN). Key age-related clinical, epidemiological, and treatment features of zoster and PHN are reviewed. HZ is caused by renewed replication and spread of varicella-zoster virus (VZV) in sensory ganglia and afferent peripheral nerves in the setting of age-related, disease-related, and drug-related decline in cellular immunity to VZV. VZV-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities of daily living, and reduced quality of life in elderly patients. Recently, attempts to reduce or eliminate HZ pain have been bolstered by the findings of clinical trials that antiviral agents and corticosteroids are effective treatment for HZ and that tricyclic antidepressants, topical lidocaine, gabapentin, and opiates are effective treatment for PHN. Although these advances have helped, PHN remains a difficult condition to prevent and treat in many elderly patients.

To determine if a visual intervention (medication grid) delivered to physicians can reduce medication regimen complexity.Nonrandomized, controlled trial.Veterans Affairs medical center.Eight hundred thirty-six patients taking at least 5 medications at the time of admission and the 48 teams of physicians and students on the general medicine inpatient service.For intervention patients, a medication grid was created that displayed all of the patients' medicines and the times of administration for 1 week. This grid was delivered to the admitting resident soon after admission.For the patients of each team of physicians, we calculated the change in the average number of medications and doses from admission to discharge. The number of medications in the intervention group decreased by 0.92 per patient, and increased by 1.65 in the control group (P.001). The mean number of doses per day in the intervention group decreased by 2.47 per patient and increased by 3.83 in the control group (P.001).This simple intervention had a significant impact on medication regimen complexity in this population. Apparently, physicians were able to address polypharmacy when the issue was brought to their attention.