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Background:Clinicians and laboratories routinely use urinalysis (UA) parameters to determine whether antimicrobial treatment and/or urine cultures are needed. Yet the performance of individual UA parameters and common thresholds for action are not well defined and may vary across different patient populations.Methods:In this retrospective cohort study, we included all encounters with UAs ordered 24 hours prior to a urine culture between 2015 and 2020 at 3 North Carolina hospitals. We evaluated the performance of relevant UA parameters as potential outcome predictors, including sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria and used receiver operating curves to identify the 5 best-performing models for predicting significant bacteriuria (≥100,000 colony-forming units of bacteria/mL).Results:In 221,933 encounters during the 6-year study period, no single UA parameter had both high sensitivity and high specificity in predicting bacteriuria. Absence of leukocyte esterase and pyuria had a high NPV for significant bacteriuria. Combined UA parameters did not perform better than pyuria alone with regard to NPV. The high NPV ≥0.90 of pyuria was maintained among most patient subgroups except females aged ≥65 years and patients with indwelling catheters.Conclusion:When used as a part of a diagnostic workup, UA parameters should be leveraged for their NPV instead of sensitivity. Because many laboratories and hospitals use reflex urine culture algorithms, their workflow should include clinical decision support and or education to target symptomatic patients and focus on populations where absence of pyuria has high NPV.

Antibiotics are among the leading causes of adverse drug events in older adults. Short-course antibiotic therapy has been shown to work as well as the traditional longer durations for many types of infections. Antibiotic stewardship interventions including deprescribing strategies have shown a reduction in patient readmissions and mortality among older adults. We identified practice-changing clinical trials focusing on three major domains of overprescribing antibiotics in older adults - community-acquired pneumonia, urinary tract infections, and gram-negative bacteremia. The selected articles underscore the safety and effectiveness of shorter durations of antibiotic treatment for infections in older adults, thus highlighting an opportunity for deprescribing in the aging population. By optimizing antibiotic use, we stand to reduce adverse events and enhance overall health outcomes in older adults.

BACKGROUND: Piperacillin/tazobactam is one of the most frequently used antimicrobials in older adults. INTRODUCTION: Using an opportunistic study design we evaluated the pharmacokinetics (PK) of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults. METHODS: A total of 121 adult patients were included. The population PK models that best characterized the observed plasma concentrations of piperacillin and tazobactam were one-compartment structural models with zero-order input and linear elimination. RESULTS: Among all potential covariates, estimated creatinine clearance had the most substantial impact on the elimination clearance for both piperacillin and tazobactam. After accounting for renal function and body size, there was no remaining impact of frailty on the PK of piperacillin and tazobactam. Monte Carlo simulations indicated that renal function had a greater impact on the therapeutic target attainment than age, although these covariates were highly correlated. Frailty, using the Canadian Study of Health and Aging Clinical Frailty Scale, was assessed in 60 patients who were ≥65 years of age. CONCLUSION: The simulations suggested that adults ≤50 years of age infected with organisms with higher minimum inhibitory concentrations (MICs) may benefit from continuous piperacillin/tazobactam infusions (12 g/day of piperacillin component) or extended infusions of 4 g every 8 hours. However, for a target of 50% fT>MIC, dosing based on renal function is generally preferable to dosing by age, and simulations suggested that patients with creatinine clearance ≥120 mL/min may benefit from infusions of 4 g every 8 hours for organisms with higher MICs.

PURPOSE: The etiology of postmenopausal recurrent urinary tract infection (UTI) is not completely known, but the urinary microbiome is thought to be implicated. We compared the urinary microbiome in menopausal women with recurrent UTIs to age-matched controls, both in the absence of acute infection. MATERIALS AND METHODS: This is a cross-sectional analysis of baseline data from 64 women enrolled in a longitudinal cohort study. All women were using topically applied vaginal estrogen. Women >55 years of age from the following groups were enrolled: 1) recurrent UTIs on daily antibiotic prophylaxis; 2) recurrent UTIs not on antibiotic prophylaxis; and 3) age-matched controls without recurrent UTIs. Catheterized urine samples were collected at least 4 weeks after last treatment for UTI and at least 6 weeks after initiation of vaginal estrogen. Samples were evaluated using expanded quantitative urine culture (EQUC) and 16S rRNA gene sequencing. RESULTS: With EQUC, there were no significant differences in median numbers of microbial species isolated among groups (p=0.96), even when considering Lactobacilli (p=0.72). However, there were trends towards different Lactobacillus species between groups. With 16S rRNA sequencing, the majority of urinary samples contained Lactobacilli, with non-significant trends in relative abundance of Lactobacilli among groups. Using a Bayesian analysis, we identified significant differences in anaerobic taxa associated with phenotypic groups. Most of these differences centered on Bacteroidales and the family Prevotellaceae, though differences were also noted in Actinobacteria and certain genera of Clostridiales. CONCLUSIONS: Associations between anaerobes within the urinary microbiome and postmenopausal recurrent UTI warrants further investigation.

ObjectiveTo develop a new caregiver-assisted pain coping skills training protocol specifically tailored for community-dwelling persons with cognitive impairment and pain, and assess its feasibility and acceptability.MethodIn Phase I, we conducted interviews with 10 patient–caregiver dyads to gather feedback about intervention content and delivery. Phase II was a single-arm pilot test to evaluate the intervention's feasibility and acceptability. Dyads in the pilot study (n = 11) completed baseline surveys, received five intervention sessions, and then completed post-intervention surveys. Analyses focused on feasibility and acceptability.ResultsDyads responded positively to the pain coping skills presented in the interviews; their feedback was used to refine the intervention. Findings from the pilot study suggested that the intervention was feasible and acceptable. 69% of eligible dyads consented, 82% completed all five intervention sessions, and 100% completed the post-treatment assessment. Caregivers reported high satisfaction ratings. They also reported using the pain coping skills on a regular basis, and that they found most of the skills helpful and easy to use.Significance of resultsThese preliminary findings suggest that a caregiver-assisted pain coping skills intervention is feasible and acceptable, and that it may be a promising approach to managing pain in patients with cognitive impairment.

Background Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. Methods We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 μg or 15 μg hemagglutinin (HA); two doses of 15 μg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 μg or 15 μg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 μg or 15 μg HA, or 15 μg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. Results We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 μg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 μg adjuvanted groups. Conclusions Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases

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

Improving the quality of medication use and medication safety are important priorities for prescribers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2019. We selected high-quality studies that moved the field of research forward and were not merely replication studies. The chosen articles cover domains related to aspects of suboptimal prescribing and medication safety. The first study used a nationally representative sample of Medicare beneficiaries to examine the continuation of medications with limited benefit in patients admitted for cancer and non-cancer diagnoses in hospice (domain: potentially inappropriate medications). The second study, a retrospective cohort study of older adults in Ontario, Canada, assessed the association between prescribing oral anticoagulants in an emergency department relative to not prescribing anticoagulants in the emergency department and their persistence at 6 months (domain: underuse of medications). The third study, a cluster randomized trial in Quebec, Canada, evaluated the effect of conducting electronic medication reconciliation on several outcomes including adverse drug events and medication discrepancies (domain: medication safety). Lastly, the fourth study, a retrospective study using national inpatient and outpatient Veteran Health Administration combined with clinical and Medicare Claims data, examined the effects of intensification of antihypertensive medications on older adults' likelihood for hospital re-admission and other important clinical outcomes (domain: medication safety). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens Refereed/Peer-reviewed

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.

Function and the independent performance of daily activities are of critical importance to older adults. Although function was once a domain of interest primarily limited to geriatricians, transdisciplinary research has demonstrated its value across the spectrum of medical and surgical care. Nonetheless, integrating a functional perspective into medical and surgical therapeutics has yet to be implemented consistently into clinical practice. This article summarizes the presentations and discussions from a workshop, "Embedding/Sustaining a Focus on Function in Specialty Research and Care," held on January 31 to February 1, 2019. The third in a series supported by the National Institute on Aging and the John A. Hartford Foundation, the workshop aimed to identify scientific gaps and recommend research strategies to advance the implementation of function in care of older adults. Transdisciplinary leaders discussed implementation of mobility programs and functional assessments, including comprehensive geriatric assessment; integrating cognitive and sensory functional assessments; the role of culture, environment, and community in incorporating function into research; innovative methods to better identify functional limitations, techniques, and interventions to facilitate functional gains; and the role of the health system in fostering integration of function. Workshop participants emphasized the importance of aligning goals and assessments and adopting a team science approach that includes clinicians and frontline staff in the planning, development, testing, and implementation of tools and initiatives. This article summarizes those discussions.

Purpose We investigated the association between location of acquisition (LOA) of gram-positive (GP) bloodstream infections (BSI) in community hospitals and clinical outcomes. Methods We performed a multicenter cohort study of adult inpatients with GP BSI in nine community hospitals from 2003 to 2006. LOA was defined by CDC criteria: 1) community-acquired (CA), 2) healthcare-associated (HCA) such as BSI

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.

Improving the quality of medication use and medication safety are important priorities for prescribers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2020. We selected high-quality studies that moved the field of research forward and were not merely replication studies. The chosen articles cover domains related to deprescribing, medication safety, and optimizing medication use. The first study, a noninferiority randomized clinical trial in England, evaluated whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events over the 12-week follow-up (domain: deprescribing). The second study, a prospective cohort study of women at Kaiser Permanente Southern, California, examined the association between bisphosphonate use and atypical femur fracture (domain: medication safety). The third study examined the effectiveness and safety of a multifaceted antimicrobial stewardship and quality improvement initiative in reducing unnecessary antimicrobial use for unlikely cystitis cases in noncatheterized residents in 25 nursing homes across the United States (domain: optimizing medication use). Lastly, the fourth study, a population-based cohort study in the United Kingdom, examined the association of tramadol use with risk of hip fracture (domain: medication safety). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens. Refereed/Peer-reviewed

Background The BNT162b2 SARS-CoV-2 mRNA vaccination has mitigated the burden of COVID-19 among residents of long-term care facilities considerably, despite being excluded from the vaccine trials. Data on reactogenicity (vaccine side effects) in this population are limited. Aims To assess reactogenicity among nursing home (NH) residents. To provide a plausible proxy for predicting vaccine response among this population. Methods We enrolled and sampled NH residents and community-dwelling healthcare workers who received the BNT162b2 mRNA vaccine, to assess local or systemic reactogenicity and antibody levels (immunogenicity). Results NH residents reported reactions at a much lower frequency and lesser severity than the community-dwelling healthcare workers. These reactions were mild and transient with all subjects experiencing more local than systemic reactions. Based on our reactogenicity and immunogenicity data, we developed a linear regression model predicting log-transformed anti-spike, anti-receptor-binding domain (RBD), and neutralizing titers, with a dichotomous variable indicating the presence or absence of reported reactions which revealed a statistically significant effect, with estimated shifts in log-transformed titers ranging from 0.32 to 0.37 (all p Discussion With a significantly lower incidence of post-vaccination reactions among NH residents as reported in this study, the BNT162b2 mRNA vaccine appears to be well-tolerated among this vulnerable population. If validated in larger populations, absence of reactogenicity could help guide clinicians in prioritizing vaccine boosters. Conclusions Reactogenicity is significantly mild among nursing home residents and overall, subjects who reported post-vaccination reactions developed higher antibody titers.

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.

Recurrent urinary tract infections (UTI) are highly prevalent in postmenopausal women, where vaginal estrogen and prophylactic antibiotics are used for treatment. The etiology of recurrent UTIs is not completely known, but the urinary microbiome is thought to be implicated. Thus, we aimed to compare the “steady state” urinary microbiome in three groups of menopausal women who were all using topically-applied vaginal estrogen: 1) women with recurrent UTIs on daily antibiotic prophylaxis; 2) women with recurrent UTIs not on antibiotic prophylaxis; and 3) age-matched controls without recurrent UTIs. Here we present a cross-sectional analysis of baseline data from 64 women enrolled in a longitudinal cohort study. Catheterized urine samples were collected > 4 weeks after last treatment for UTI. Samples were evaluated using expanded quantitative urine culture (EQUC) and 16S rRNA gene sequencing. With EQUC techniques, there were no significant differences in the median numbers of microbial species isolated among groups (p=0.96), even when considering Lactobacilli (p=0.72). However, there were trends towards different Lactobacillus species between groups. With sequencing the overwhelming majority of urinary samples contained Lactobacilli, with non-significant trends in relative abundance of Lactobacilli among groups. Using a Bayesian regression analysis for compositional data, we identified significant differences in anaerobic taxa that were associated with phenotypic groups. Most of these differences centered on Bacteroidales and the family Prevotellaceae, though differences were also noted in Actinobacteria and certain genera of Clostridiales. Associations between anaerobes within the urinary microbiome and recurrent UTI warrants further investigation.IMPORTANCEIn menopausal women with recurrent urinary tract infections (UTIs) compared to those without, the abundance of Lactobacillus within the urinary microbiome is not significantly different when vaginal estrogen is regularly used. In this population, Lactobacillaceae were identified in 97% of urine samples using culture-independent techniques. However, with expanded urine cultures, women with recurrent UTIs taking daily antibiotics had a disproportionately low amount of L. gasseri/L. acidophilus compared to the other phenotypic groups. These findings support the theory that certain Lactobacillus species may be more important than others in the pathophysiology of postmenopausal recurrent UTIs. Furthermore, when using culture-independent techniques to explore urinary microbiota across phenotypic groups, we identified differences in multiple anaerobic taxa. Taken together, these results suggest that altered ratios of anaerobes and certain Lactobacillus species within the urinary microbiome may be implicated in postmenopausal recurrent UTI.

BACKGROUND The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. METHODS 479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. RESULTS Subjects in all groups had only modest immune responses, with the HAI GMT

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.

Background The elderly patient population is the most susceptible to influenza virus infection and its associated complications. Polypharmacy is common in the aged, who often have multiple co-morbidities. Previous studies have demonstrated that commonly used prescription drugs can have extensive impact on immune defenses and responses to vaccination. In this study, we examined how the dynamics of immune responses to the two influenza A virus strains of the trivalent inactivated influenza vaccine (TIV) can be affected by patient’s history of using the prescription drugs Metformin, NSAIDs or Statins. Results We provide evidence for differential antibody (Ab) production, B-cell phenotypic changes, alteration in immune cell proportions and transcriptome-wide perturbation in individuals with a history of long-term medication use, compared with non-users. We noted a diminished response to TIV in the elderly on Metformin, whereas those on NSAIDs or Statins had higher baseline responses but reduced relative increases in virus-neutralizing Abs (VNAs) or Abs detected by an enzyme-linked immunosorbent assay (ELISA) following vaccination. Conclusion Collectively, our findings suggest novel pathways that might underlie how long-term medication use impacts immune response to influenza vaccination in the elderly. They provide a strong rationale for targeting the medication-immunity interaction in the aged population to improve vaccination responses. Electronic supplementary material The online version of this article (10.1186/s12979-018-0124-9) contains supplementary material, which is available to authorized users.

Background Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine’s elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012–2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). Methods We investigated the basis of low VE in 2012–2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. Results We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. Conclusions In contrast to analyses based on ferret studies, low H3N2 VE in 2012–2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population., Low H3N2 vaccine effectiveness in 2012–2013 appears attributable to low vaccine immunogenicity in a subset of adults, and not the induction of a narrow, specific response to the egg-adapted strain suggested by previous experiments in immunologically naive ferrets.

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.

Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as increased vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, HIV care, nephrology, and in the behavioral and social sciences. Incorporation of frailty assessment and frailty research into the specialties is hindered by a lack of a consensus definition, by the proliferation of measurement tools, inadequate understanding of the biology of frailty, and lack of validated clinical algorithms for patients who have frailty. In 2015, the American Geriatrics Society, the National Institute on Aging (NIA) and the Alliance for Academic Internal Medicine held a conference for awardees of the NIA sponsored ‘Grants for Early Medical/Surgical Specialists Transition into Aging Research (GEMSSTAR)’1 program to review the current state of the knowledge regarding frailty in the sub-specialties, as well as to highlight key examples of integrating frailty research into the medical specialties. Key research questions to advance frailty research into specialty medicine are proposed.

Background Herpes zoster can negatively impact older adults’ health and quality of life. An adjuvanted recombinant zoster vaccine (RZV) has excellent vaccine efficacy (VE), including in older adults. Given that frailty is strongly associated with vulnerability to illness and adverse health outcomes, we studied how frailty impacts RZV VE, immunogenicity, reactogenicity, and safety. Methods In the ZOE-50 and ZOE-70 pivotal Phase 3 efficacy studies of RZV, 29,305 participants aged 50–96 received 2 doses of RZV vs. placebo in 1:1 randomization. In this secondary analysis (NCT03563183), a baseline frailty index (FI) was created retrospectively following previously validated methods using pre-existing comorbidities and patient reported outcomes. Participants were categorized as non-frail (FI≤ 0.08), pre-frail (FI=0.08–0.25) or frail (FI≥ 0.25) for stratified analyses. Results FI was calculated for 99.8% of participants included in this secondary analysis (n=26,976), and was balanced between RZV and placebo groups. 45.6% were pre-frail and 11.3% were frail. Mean age was 68.8 years; 58.1% were women. RZV VE against HZ was consistently above 90% for all frailty categories [non-frail: 95.8% (95%CI: 91.6–98.2), pre-frail: 90.4% (84.4–94.4), frail: 90.2% (75.4–97.0)]. The RZV group demonstrated robust antibody responses post-dose 2 across frailty categories. In the RZV group, the percentage of participants reporting solicited adverse events decreased with increasing frailty. Unsolicited medically attended visits and serious adverse events increased with frailty and were balanced between placebo and RZV groups. Conclusion The ZOE studies included older adults who were frail and pre-frail, and VE was high across frailty categories. Reactogenicity decreased with increasing frailty, and no safety concerns were identified in any frailty group. Disclosures Melissa K. Andrew, MD, PhD, MSc(Ph), GSK (Grant/Research Support, Research Grant or Support) Joon Hyung Kim, MD, GSK (Employee, Shareholder) Sean Matthews, MSc, GSK (Consultant) Christophe Dessart, MSc, GSK (Employee) myron J. levin, MD, Curevo (Advisor or Review Panel member)GlaxoSmithKline (Grant/Research Support, Advisor or Review Panel member)GlaxoSmithKline (Grant/Research Support, Advisor or Review Panel member)Merck Research Laboratories (Advisor or Review Panel member, GlaxoSmithKline)Merck Research Laboratories (Advisor or Review Panel member)Merck ResearchLaboratories (Advisor or Review Panel member) Lidia Oostvogels, MD, GSK (Shareholder) Megan Riley, PhD, GSK (Employee) Shelly McNeil, FRCPC, MD, GSK (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support, honoraria for talks) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration) Desmond Curran, PhD, GSK (Employee, Shareholder)

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.

Humoral immune responses are dysregulated with aging but details remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the subset that provides critical help to B cells for effective humoral immunity. We previously demonstrated that influenza vaccination increases a circulating Tfh (cTfh) subset that expresses ICOS and CD38, contains influenza-specific memory cells, and is correlated with antibody responses. To directly study the effects of aging on the cTfh response, we performed transcriptional profiling and cellular analysis before and after influenza vaccination in young and elderly adults. Several key differences in cTfh responses were revealed in the elderly. First, whole blood transcriptional profiling defined cross-validated genesets of youth versus aging and these genesets were, compared to other T cells, preferentially enriched in ICOS+CD38+ cTfh from young and elderly subjects, respectively, following vaccination. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly were enriched for transcriptional signatures of inflammation including TNF-NFkB pathway activation. Indeed, we reveal a paradoxical positive effect of TNF signaling on Tfh providing help to B cells linked to survival circuits that may explain detrimental effects of TNF blockade on vaccine responses. Finally, vaccine-induced ICOS+CD38+ cTfh displayed strong enrichment for signatures of underlying age-associated biological changes. Thus, these data reveal key biological changes in cTfh during aging and also demonstrate the sensitivity of vaccine-induced cTfh to underlying changes in host physiology. This latter observation suggests that vaccine-induced cTfh could function as sensitive biosensors of underlying inflammatory and/or overall immune health.One sentence summaryTranscriptional profiling of vaccine-induced circulating T follicular helper cell responding to influenza vaccination reveals age-associated effects on Tfh such as alterations in TNF-NFkB signaling.

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.

Importance Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference −2.7%; 95% CI, −5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study’s results support using either vaccine to prevent influenza in older adults. Trial Registration ClinicalTrials.gov Identifier:NCT03183908

// 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.

Medication errors and adverse drug events are common in older adults, but locating literature addressing these issues is often challenging. The objective of this article is to summarize recent studies addressing medication errors and adverse drug events in a single location to improve accessibility for individuals working with older adults. A comprehensive literature search for studies published in 2014 was conducted, and 51 potential articles were identified. After critical review, 17 studies were selected for inclusion based on innovation; rigorous observational or experimental study designs; and use of reliable, valid measures. Four articles characterizing potentially inappropriate prescribing and interventions to optimize medication regimens were annotated and critiqued in detail. The authors hope that health policy-makers and clinicians find this information helpful in improving the quality of care for older adults.

Exercise is touted as the ideal prescription to treat and prevent many chronic diseases. We examined changes in utilization and cost of medication classes commonly prescribed in the management of chronic conditions following participation in 12-months of supervised exercise within the Veterans Affairs Gerofit program. Gerofit enrolled 480 veterans between 1999 and 2017 with 12-months participation, with 453 having one or more active prescriptions on enrollment. Active prescriptions overall and for five classes of medications were examined. Changes from enrollment to 12 months were calculated, and cost associated with prescriptions filled were used to estimate net cost changes. Active prescriptions were reduced for opioids (77 of 164, 47%), mental health (93 of 221, 42%), cardiac (175 of 391, 45%), diabetes (41 of 166, 25%), and lipid lowering (56 of 253, 22%) agents. Cost estimates resulted in a net savings of $38,400. These findings support the role of supervised exercise as a favorable therapeutic intervention that has impact across chronic conditions.

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.

Little research has been done on primary care–based models to improve health care use after an emergency department (ED) visit. To examine the effectiveness of a primary care–based, nurse telephone support intervention for Veterans treated and released from the ED. Randomized controlled trial with 1:1 assignment to telephone support intervention or usual care arms (ClinicalTrials.gov: NCT01717976). Department of Veterans Affairs Health Care System (VAHCS) in Durham, NC. Five hundred thirteen Veterans who were at high risk for repeat ED visits. The telephone support intervention consisted of two core calls in the week following an ED visit. Call content focused on improving the ED to primary care transition, enhancing chronic disease management, and educating Veterans and family members about VHA and community services. The primary outcome was repeat ED use within 30 days. Observed rates of repeat ED use at 30 days in usual care and intervention groups were 23.1% and 24.9%, respectively (OR = 1.1; 95% CI = 0.7, 1.7; P = 0.6). The intervention group had a higher rate of having at least 1 primary care visit at 30 days (OR = 1.6, 95% CI = 1.1–2.3). At 180 days, the intervention group had a higher rate of usage of a weight management program (OR = 3.5, 95% CI = 1.6–7.5), diabetes/nutrition (OR = 1.8, 95% CI = 1.0–3.0), and home telehealth services (OR = 1.7, 95% CI = 1.0–2.9) compared with usual care. A brief primary care–based nurse telephone support program after an ED visit did not reduce repeat ED visits within 30 days, despite intervention participants’ increased engagement with primary care and some chronic disease management services. ClinicalTrials.gov NCT01717976.

Improving the quality of medication use and medication safety in older adults is an important public health priority and is of paramount importance for clinicians who care for them. We selected four important articles from 2017 that address these issues to annotate and critique, and we discuss the broader implications for optimizing medication use. A longer list of articles is given in an online appendix. The first study provides national data on the prevalence of central nervous system-active medication polypharmacy in older adults and how this has changed over a 9-year period (2004-2013). The second study characterizes prevalence of and factors associated with nonadherence to antiepileptic drugs in 36,912 older adults with epilepsy, with an emphasis on minorities. The third study describes the extent of antibiotic use in residents of 381 long-term care facilities (LTCF) in British Columbia, Canada, from 2007 to 2014. Finally, we discuss a meta-analysis of 42 studies that evaluated the prevalence of hospital admissions caused by adverse drug reactions in older adults. This article is intended to provide a narrative review of important publications on medication use quality and safety for clinicians and researchers committed to optimizing medication use in older adults. J Am Geriatr Soc 66:2254-2258, 2018.

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.