High-risk Comorbid Conditions Research Articles

Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.

Characteristics and Trends in HIV Testing Among Medicaid Enrollees Diagnosed as Having Schizophrenia.

People with schizophrenia have more HIV risk factors and higher rates of HIV infection than the general U.S. population. The authors aimed to examine HIV testing patterns in this population nationally and by demographic characteristics and presence of high-risk comorbid conditions. This retrospective longitudinal study compared HIV testing between Medicaid-only enrollees with schizophrenia and without schizophrenia during 2002-2012 (N=6,849,351). Interrupted time series were used to analyze the impacts of the 2006 federal policy change recommending expanded HIV testing. Among enrollees with schizophrenia, multivariable logistic regression was used to estimate associations between testing and both demographic characteristics and comorbid conditions. Sensitivity analyses were also conducted. Enrollees diagnosed as having schizophrenia had consistently higher HIV testing rates than those without schizophrenia. When those with comorbid substance use disorders or sexually transmitted infections were excluded, testing was higher for individuals without schizophrenia (p<0.001). The federal policy change likely increased testing for both groups (p<0.001), but the net change was greater for those without schizophrenia (3.1 vs. 2.2 percentage points). Among enrollees with schizophrenia, testing rates doubled during 2002-2012 (3.9% to 7.2%), varied across states (range 17 percentage points), and tripled for those with at least one annual nonpsychiatric medical visit (vs. no visit; adjusted OR=3.10, 95% CI=2.99-3.22). Nationally, <10% of enrollees with schizophrenia had annual HIV testing. Increases appear to be driven by high-risk comorbid conditions and nonpsychiatric encounters, rather than by efforts to target people with schizophrenia. Psychiatric guidelines for schizophrenia care should consider HIV testing alongside annual metabolic screening.

Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines

Evidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations. To describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose. Retrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration-authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants. Receipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose. Outcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions. Of 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions. In a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.

Reliable cognitive change following unilateral deep brain stimulation in essential tremor

Objective: This retrospective analysis assessed regression-based reliable change (RC) of cognition in a sample of essential tremor (ET) patients who underwent unilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS). Method: Thirty patients (mean age at pre-evaluation = 70.4 ± 6.3 years) underwent neuropsychological evaluation pre- and post-unilateral VIM-DBS placement (mean time between pre and post-evaluation = 13.1 ± 4.0 months). Paired samples t-tests and RC analyses were employed. Results: No significant within-group differences were observed when cognitive scores were compared between evaluations. The vast majority of patients demonstrated stability across pre-and post-surgical evaluations (i.e. 29 out of 30); however, those with high-risk co-morbid medical conditions may be vulnerable to post-surgical cognitive decline as indicated by RC measures. Conclusions: The use of regression-based RC indices to assess individual cognitive changes between pre and post-surgical evaluations control for systematic and measurement errors that can occur over repeated evaluations, and may be able to identify cognitive changes that evade detection in traditional within-group comparisons.

Health Status, Persistent Symptoms, and Effort Intolerance One Year After Acute COVID-19 Infection.

BackgroundThe long-term prevalence and risk factors for post-acute COVID-19 sequelae (PASC) are not well described and may have important implications for unvaccinated populations and policy makers.ObjectiveTo assess health status, persistent symptoms, and effort tolerance approximately 1 year after COVID-19 infectionDesignRetrospective observational cohort study using surveys and clinical dataParticipantsSurvey respondents who were survivors of acute COVID-19 infection requiring Emergency Department presentation or hospitalization between March 3 and May 15, 2020.Main Measure(s)Self-reported health status, persistent symptoms, and effort toleranceKey ResultsThe 530 respondents (median time between hospital presentation and survey 332 days [IQR 325–344]) had mean age 59.2±16.3 years, 44.5% were female and 70.8% were non-White. Of these, 41.5% reported worse health compared to a year prior, 44.2% reported persistent symptoms, 36.2% reported limitations in lifting/carrying groceries, 35.5% reported limitations climbing one flight of stairs, 38.1% reported limitations bending/kneeling/stooping, and 22.1% reported limitations walking one block. Even those without high-risk comorbid conditions and those seen only in the Emergency Department (but not hospitalized) experienced significant deterioration in health, persistent symptoms, and limitations in effort tolerance. Women (adjusted relative risk ratio [aRRR] 1.26, 95% CI 1.01–1.56), those requiring mechanical ventilation (aRRR 1.48, 1.02–2.14), and people with HIV (aRRR 1.75, 1.14–2.69) were significantly more likely to report persistent symptoms. Age and other risk factors for more severe COVID-19 illness were not associated with increased risk of PASC.ConclusionsPASC may be extraordinarily common 1 year after COVID-19, and these symptoms are sufficiently severe to impact the daily exercise tolerance of patients. PASC symptoms are broadly distributed, are not limited to one specific patient group, and appear to be unrelated to age. These data have implications for vaccine hesitant individuals, policy makers, and physicians managing the emerging longer-term yet unknown impact of the COVID-19 pandemic.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07379-z.

1422. Real-World Study of the Effects of Inappropriate or Suboptimal Treatment on the Burden of Illness Among Patients with Uncomplicated Urinary Tract Infection and High-Risk Comorbid Conditions in the United States

Abstract Background Urinary tract infections (UTIs) are associated with significant morbidity and economic burden. Nitrofurantoin (NFT) and fosfomycin are among the first-line treatments for uncomplicated UTI (uUTI) recommended by Infectious Diseases Society of America (IDSA) 2011 guidance. We used real-world data (RWD) to assess patterns of appropriate and optimal (AP&amp;OP) and inappropriate or suboptimal (IA/SO) antibiotic (AB) prescribing (RX), and related healthcare resource use (HRU) and costs, in US uUTI patients with high-risk comorbid conditions. Methods This was a retrospective cohort study of RWD (IBM MarketScan, commercial/Medicare Supplemental claims January 1, 2014–December 31, 2017) in females ≥ 12 years of age with uUTI, who had an oral AB prescription ± 5 days of uUTI diagnosis (index date) and continuous health-plan enrollment ≥ 1 year pre-/post-index date. Patients were stratified into high-risk cohorts (Table 1) and by AB RX (AP&amp;OP and IA/SO) during first uUTI episode (within 28 days of index). AP&amp;OP RX followed IDSA guidance, IA RX did not; SO RX was considered a proxy for treatment failure (e.g., AB switch or a second UTI diagnosis [acute care setting] in index episode). Sample size was balanced via random match selection, AP&amp;OP:IA/SO ratio 1:5 (age and region). uUTIrelated HRU and costs were compared between cohorts (at index episode and 1-year follow-up) via multivariable analysis. Table 1. High-risk cohorts identified in the study Results IA/SO AB RX was highest in the elderly cohort (94.3%, likely influenced by renal impairment/no NFT RX in this group) and &amp;gt; 90% in other cohorts; AP&amp;OP AB RX was highest in the postmenopausal cohort (9.0%). IA/SO AB RX in all cohorts was associated with significantly higher uUTI-related HRU (outpatient visits and pharmacy claims) per index episode/during follow-up versus AP&amp;OP AB RX (p ≤ 0.0237, Table 2). IA/SO AB RX in all cohorts was associated with significantly higher adjusted total costs per index episode/during follow-up versus AP&amp;OP AB RX (p &amp;lt; 0.05; Table 3). Table 2. uUTI-related HRU* per patient according to high-risk cohort and stratified by AB RX Table 3. uUTI-related costs* per patient according to high-risk cohort and stratified by AB RX Conclusion Over 90% of females in each high-risk cohort identified had IA/SO AB RX (outside IDSA 2011 guidance for uUTI treatment), leading to high HRU and cost burden. This suggests an unmet need for uUTI symptom relief, new treatments, training, and improved RX practices in the US and, furthermore, a need for additional research in this area. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

1429. Real-World Study of Patients with Uncomplicated Urinary Tract Infection in the United States: High-Risk Comorbid Conditions and Burden of Illness

BackgroundUrinary tract infections (UTIs) are associated with significant morbidity and economic burden, particularly in the elderly and patients with comorbidities. We used real-world data (RWD) to assess healthcare resource use (HRU) and costs in patients with uncomplicated UTI (uUTI) and high-risk comorbid conditions in the US.MethodsThis was a retrospective cohort study (IBM MarketScan RWD, commercial/Medicare Supplemental claims January 1, 2014–December 31, 2017) of females ≥ 12 years of age with uUTI who had an oral antibiotic prescription ± 5 days of uUTI diagnosis (index date) and continuous health-plan enrollment for ≥ 1 year pre-/post index date. Five high-risk cohorts and matched-control cohorts (baseline age, region) were identified: controlled type 2 diabetes (T2D), mild/moderate chronic kidney disease (CKD), recurrent UTI (rUTI), elderly (ELD), and postmenopausal (PMP) (Table 1). Sample sizes were balanced via random match selection (1:5 case:control). uUTI-related HRU and costs were compared between cases and controls (index episode/1-year follow-up) using multivariable generalized linear models.Table 1. Cohort assignment for high-risk cohorts and controls ResultsOf 339,100 patients with uUTI, case/control cohorts comprised T2D, n=15,423/n=77,115; CKD, n=1041/n=5205; rUTI, n=7937/n=39,685; ELD, n=23,666/n=118,330; and PMP, n=105,608/n=211,216 patients. HRU trends across cohorts varied. During 1-year followup, outpatient visits were significantly different for cases versus controls in the T2D, rUTI, and PMP cohorts (p ≤ 0.0079), with higher case than control values in the rUTI and PMP cohorts; pharmacy claims were significantly higher for rUTI, ELD, and PMP cases, and inpatient visits were significantly higher for ELD and PMP cases, versus controls (all p < 0.0001; Table 2). Adjusted total uUTI-related costs (emergency room + outpatient + pharmacy) were significantly different (p < 0.0001) for cases versus controls at index episode and during follow-up in all cohorts except CKD: case values were higher than controls at index episode and during follow-up in the T2D cohort, and during follow-up in the rUTI and ELD cohorts (Table 3).Table 2. uUTI-related HRU* for cases versus controls according to high-risk cohort Table 3. uUTI-related costs* for cases versus controls according to high-risk cohort ConclusionFemales in some high-risk case cohorts had higher uUTI-related HRU and costs versus controls. Further studies of relationships between comorbidities and uUTI burden are needed.Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Coronavirus disease 2019 and neurodegenerative disease: what will the future bring?

Purpose of reviewOver 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals.Recent findingsBased on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration.SummarySince patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.

1499. Incidence of Community Acquired Pneumonia by Age and Comorbid Conditions in the Veterans Health Administration (VHA)

BackgroundCommunity acquired pneumonia (CAP) remains a major cause of morbidity and mortality. Risk factors for CAP are often grouped as moderate- (e.g., diabetes mellitus, chronic liver, lung, or heart disease) and high-risk (e.g., immunosuppressive) conditions, which in turn influences preventative strategies, notably pneumococcal vaccination. Here, we use the national VHA databases to assess the risk of CAP among adults, expanding on previous work by using administrative data to assess the incidence of CAP among people with > 1 moderate risk conditionMethodsWe used the national VHA databases merged with claims summaries from the Centers for Medicare and Medicaid Services (CMS) to identify patients receiving clinical care in the VHA without clinical Medicare claims in 2016-2017. Within this population, we identified CAP cases defined by the presence of a diagnostic code for pneumonia, chest X-ray, and antibiotics as well as the absence of healthcare exposure or antibiotics in prior 90 days. We determined the total patient years at risk and calculated incidence rates by age group and by moderate- and high-risk comorbid conditions.ResultsWe identified 37,348 CAP cases in 7.9 million person-years at risk and observed similar annual rates in 2016 and 2017 (468.9 and 472.2 cases/100,000 person-years, respectively). The prevalence of high-risk conditions and incidence of CAP increased with age whereas the prevalence of >1 moderate-risk condition peaked for ages 50-64 and 65-74 years (Table). The incidence of CAP among those with > 1 moderate-risk condition exceeded that of patients with high-risk conditions across all age strata (Figure).Table Figure ConclusionAge-adjusted analysis revealed that the greatest burden of CAP occurs in patients with > 1 moderate-risk condition, even compared to those with a high-risk condition. Our analysis of CAP based on national VHA data suggest that additional preventative health measures directed at individuals older than 50 years with > 1 moderate-risk condition may help to reduce the burden of CAP and limit its morbidity and mortality.Disclosures Robin Jump, MD, PhD, Accelerate (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member) Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

The Perfect Storm: COVID-19 Health Disparities in US Blacks.

Coronavirus disease 2019 (COVID-19) accounts for over 180,000 deaths in the USA. Although COVID-19 affects all racial ethnicities, non-Hispanic Blacks have the highest mortality rates. Evidence continues to emerge, linking the disproportion of contagion and mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a result of adverse social determinants of health. Yet, genetic predisposition may also play a credible role in disease transmission. SARS-CoV-2 enters cells by interaction between SARS-CoV-2 spike protein and the receptor molecule angiotensin converting enzyme 2 (ACE2) expressed on the surface of the target cells, such that polymorphisms and the expression level of ACE2 influence infectivity and consequent pathogenesis of SARS-CoV-2. Genetic polymorphisms in other multiple genes, such as acetylcholinesterase (AChE) and interleukin-6, are also closely associated with underlying diseases, such as hypertension and type 2 diabetes mellitus, which substantially raise SARS-CoV-2 mortality. However, it is unknown how these genetic polymorphisms contribute to the disparate mortality rates, with or without underlying diseases. Of particular interest is the potential that genetic polymorphisms in these genes may be influencing the disparity of COVID-19 mortality rates in Black communities. Here, we review the evidence that biological predisposition for high-risk comorbid conditions may be relevant to our ability to fully understand and therefore address health disparities of COVID-19 deaths in Blacks.Electronic supplementary materialThe online version of this article (10.1007/s40615-020-00871-y) contains supplementary material, which is available to authorized users.

Long-term clinical outcomes after a percutaneous coronary intervention with a drug-eluting stent in patients with unprotected left main coronary artery disease excluded from clinical trials.

Major randomized clinical trials assessing clinical outcomes in patients who underwent a percutaneous coronary intervention (PCI) for left main coronary artery disease excluded some high-risk subsets. Whether the effectiveness and safety of a percutaneous approach in this group of patients are comparable with those observed in clinical trials is unclear. We aimed to explore the long-term outcomes of contemporary drug-eluting stent (DES)-based revascularization for left main coronary artery disease in patients presenting with one or more clinical or angiographic characteristics who would have precluded inclusion in randomized trials. Between April 2003 and December 2011, 340 consecutive patients with unprotected left main coronary artery stenosis of at least 50% who underwent successful PCI with DES at Sejong General Hospital (Bucheon, Republic of Korea) were included in this retrospective study. Patients were classified into the exclusion group (group E; n=120) and the inclusion group (group I; n=220) according to the prespecified inclusion and exclusion criteria utilized in clinical trials. During the median follow-up of 86 (52-114) months, major adverse cardiac or cerebrovascular events occurred in 69 (31.4%) patients in group I and 46 (38.3%) patients in group E (P=0.155). In the propensity score-matched population, group E was not associated with a higher incidence of major adverse cardiac or cerebrovascular events (hazard ratio: 1.42, 95% confidence interval: 0.76-2.65, P=0.758). Definite or probable stent thrombosis occurred in five patients of group I, with no cases in group E. In our real-world registry, about a third of patients who underwent PCI for unprotected left main coronary artery stenosis had one or more high-risk characteristics or comorbid conditions that represent exclusion criteria of previous randomized trials. PCI using DES is feasible in these patients.

Is weight associated with severity of acute respiratory illness?

Background/ObjectivesObesity was an independent risk factor for severe disease in hospitalized adults during the 2009 pandemic H1N1 influenza season. Few studies have investigated the association between weight and severity of acute respiratory illnesses in children or in adults seeking care in the emergency department (ED) during other winter respiratory seasons.Subjects/MethodsWe prospectively and systematically enrolled patients ≥2 years of age who presented to the ED or inpatient setting in a single geographic region with fever/acute respiratory illness over four consecutive winter respiratory seasons (2010–14). We collected demography, height and weight, and high risk co-morbid conditions. Multivariable logistic regression was used for prediction of hospital admission (primary outcome), length of stay and supplemental oxygen requirement among those hospitalized, and antibiotic prescription (secondary outcomes).ResultsWe enrolled 3560 patients (N=749 children, 2811 adults), 1405 (39%) with normal weight, 860 (24%) with overweight, and 1295 (36%) with obesity. Following multivariable logistic regression, very young or very old age (p<0.001) and high-risk conditions (p<0.001) predicted hospitalization. Risk of hospitalization was decreased for adults with overweight [aOR 0.8 (95% CI 0.6-1.0)], class 1 obesity [aOR 0.7 (95% CI 0.5-1.0)] and class 2 obesity [aOR 0.6 (95% CI 0.4-0.8)] compared to normal-weight. Class 3 obesity was associated with supplemental oxygen requirement in adults [aOR 1.6 (95% CI 1.1-2.5)]. No association was seen in children.ConclusionOverweight and obesity were not associated with increased risk of hospitalization during winter respiratory seasons in children or adults.

Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age, comorbidities, and frailty

BackgroundA randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest. MethodsDouble-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6–8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometric mean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions. ResultsEfficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65–74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (−3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (−9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (−16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups. ConclusionsEstimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.

Hormone therapy for radiorecurrent prostate cancer

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option. Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer. Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence. Hormone therapy remains an option for men with radiorecurrent prostate cancer.

Influenza and HIV: Lessons from the 2009 H1N1 Influenza Pandemic

Influenza is a common respiratory disease in adults, including those infected with HIV. In the spring of 2009, a pandemic influenza A (H1N1) virus (pH1N1) emerged. In this article, we review the existing literature regarding pH1N1 virus infection in HIV-infected adults, which suggests that susceptibility to pH1N1 virus infection and severity of influenza illness are likely not increased in HIV-infected adults without advanced immunosuppression or comorbid conditions. The risk of influenza-related complications, however, may be increased in those with advanced immunosuppression or high-risk comorbid conditions. Prevention and treatment of high-risk comorbid conditions and annual influenza vaccination should continue to be part of HIV clinical care to help prevent influenza illness and complications. Additional information about pH1N1 vaccine immunogenicity and efficacy in HIV-infected patients would be useful to guide strategies to prevent influenza virus infection in this population.

The Great Debate: Medicine or Surgery

In 1991, a National Institutes of Heath expert consensus panel recommended bariatric surgery to treat obesity for informed and motivated patients with BMI >40 kg/m2, or between 35 and 40 kg/m2 with high-risk comorbid conditions including diabetes, in whom operative risks are acceptable (1). In December 2010, these guidelines were reviewed by the Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee of the Food and Drug Administration, with recommendation to lower the criteria for use of the laparoscopic adjustable gastric band to BMI >30 kg/m2 for patients with comorbidity. Surgical treatments of obesity induce impressive absolute weight loss of 30–40 kg (∼60% excess weight, or a 10–15 kg/m2 reduction in BMI) (2), which may be sustained over 10–15 years (3). Increasing medical and public awareness of sustained weight loss, increased ease of recovery, and lowered complications with newer laparoscopic surgical procedures and the ongoing increased incidence of obesity have contributed to a 15-fold increase in bariatric surgical procedures in the past decade, with estimates of >200,000 procedures having been performed in the United States in 2007 (4). Recent observational studies demonstrate that bariatric surgical procedures reduce the incidence of type 2 diabetes and lead to substantial improvement or “resolution” for many patients with preexisting disease. Type 2 diabetes has “resolved” (defined in the surgical literature as maintenance of normal blood glucose after discontinuation of all diabetes-related medications, in most studies with HbA1c <7%) in ∼77% of patients who undergo obesity surgery, and resolved or improved in ∼85%, with sustained improvements in multiple metabolic measures, such as fasting plasma glucose and insulin, percent glycosylated hemoglobin, and use of antidiabetic medications (2,5–9). Patients with shorter duration of disease seem to have more complete or sustained disease resolution (10 …

Reducing mortality for chronic obstructive pulmonary disease: role of statins and angiotensin-converting enzyme inhibitors

Evaluation of: Mortensen EM, Copeland LA, Pugh MJ et al. Impact of statins and ACE-inhibitors on mortality after COPD exacerbations. Respir. Res. 10, 45 (2009).Chronic obstructive pulmonary disease (COPD) is a disease of the airways associated with increased prevalence worldwide and with increasing mortality. It is commonly associated with cardiovascular comorbid conditions and this association may impact reciprocally on disease morbidity and mortality. Statins and angiotensin-converting enzyme inhibitors are known for their effects on cardiovascular mortality reduction, and several studies have demonstrated their effects on mortality in COPD patients (particularly for statins). e study by Mortensen et al. was a large, retrospective analysis on the impact of statins and/or angiotensin-converting enzyme inhibitors prehospitalization on 90-day mortality in patients hospitalized for COPD exacerbations. It demonstrated the significant effects on mortality rate reduction of these two classes of compounds, highlighting their effects on mortality in several subsets of COPD patients with high-risk cardiovascular comorbid conditions.

In vitro results of a new minimally invasive aortic valve resecting tool☆☆☆

Aortic valve replacement (AVR) using extracorporeal circulation is currently the treatment of choice for symptomatic aortic stenosis. However, patients with multiple high-risk comorbid conditions may benefit from reduced ECC time by a simplified and faster resection in conjunction with quick sutureless valve implantation. A prototype of a new minimally invasive aortic valve resection tool equipped with rotating and foldable Nitinol cutting edges was designed. Commercially available aortic valve bioprostheses were artificially calcified (group 1: moderate calcified, n=8, group 2: severely calcified, n=8). In vitro resection was performed using a 21mm cutting blade. Resection time (RT), maximum turning moment (MTM) and number of required rotations (NR) were measured. Furthermore, particle generation during the process of cutting was obtained and quantified. Aortic valve cutting could be obtained without any complications in all cases. Cutting process resulted in a RT of 15.5+/-3s in group 1 compared to 34.9+/-15s in group 2 (p=0.005), MTM was 3+/-0.6Nm in group 1 compared to 3.5+/-0.6Nm in group 2 (p=0.068) and NR were 30.6+/-2.3 in group 1 compared to 48.1+/-15.5 in group 2 (p=0.007). Particle generation was 1.77+/-0.17g in group 1 compared to 1.41+/-0.44g in group 2 (p=0.047). These first in vitro results confirm feasibility and accelerated aortic valve resection within 30s. This new concept holds promise for very fast AVR in combination with insertion of sutureless aortic valve prosthesis, targeting for ischemic times less than 10min in the open heart situation. Finally, resection and percutaneous AVR within 1min in the beating heart situation is envisioned.

First clinical experience and 1-year follow-up with the sutureless 3F-Enable aortic valve prosthesis☆☆☆

Aortic valve replacement (AVR) with extracorporeal circulation (ECC) is currently the treatment of choice for symptomatic aortic stenosis. However, patients with multiple high-risk comorbid conditions may benefit from reduced ECC time and thus, reduced myocardial ischemia, by the use of sutureless AVR. We describe the initial experience and 1-year results of our first 3F-Enable AVR implants. Between 09/05 and 12/05, six patients (age 74+/-1.8 years; three females) with symptomatic aortic stenosis (NYHA III) underwent AVR with an equine pericardial and nitinol-stented sutureless prosthesis. For additional safety up to three stay sutures were placed. Echocardiography was performed preoperatively, intraoperatively, at 6- and 12-month follow-up. Clinical data, adverse events and patient outcome were recorded prospectively. Prosthesis sizes were 27 mm (n=3), 25 mm (n=1), 23 mm (n=1) and 21 mm (n=1). ECC time was 87+/-32 min; aortic clamp time was 56+/-24 min. Prosthesis deployment time was 148 +/- 173 s. There were no intraoperative deaths or complications. At 12-month follow-up mean pressure gradients (MPG) were 6.8+/-3.5 mmHg and aortic valve area (AVA) was 2.2 +/- 0.5 cm(2). One patient underwent successful redo AVR after 8 months due to severe paravalvular leakage (PVL), and one patient died due to lung cancer 10 months after surgery. At 12 months follow-up four out of six patients are alive and asymptotic (NYHA I) with the 3F-Enable aortic valve prosthesis, however, one patient showed mild paravalvular leakage. These first 1-year follow-up data suggest the feasibility of this new concept of sutureless aortic valve implantation. However, severe aortic insufficiency at 8 months and paravalvular leakage at 1-year follow-up should prompt further procedural and device enhancements.

Is co-morbidity taken into account in the antibiotic management of elderly patients with acute bronchitis and COPD exacerbations?

Guidelines on acute lower respiratory tract infections recommend restrictive use of antibiotics, however, in patients with relevant co-morbid conditions treatment with antibiotics should be considered. Presently, it is unknown whether GPs adhere to these guidelines and target antibiotic treatment more often at patients with risk-elevating conditions. We assessed whether in elderly primary care patients with acute bronchitis or exacerbations of chronic pulmonary disease (COPD), antibiotics are more often prescribed to patients with risk-elevating co-morbid conditions. Using the Utrecht GP research database, we analysed 2643 episodes in patients of 65 years of age or older with a GP-diagnosed acute bronchitis or exacerbation of COPD. Multivariable logistic regression analysis was applied to determine independent determinants of antibiotic use. Antibiotic prescribing rates were high in both acute bronchitis (84%) and in exacerbations of COPD (53%). In acute bronchitis, only age was an independent determinant of antibiotic use [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.003-1.048], whereas in exacerbations of COPD antibiotics were more often prescribed to male patients (OR 1.3, 95% CI 1.0-1.5), patients with diabetes (OR 1.7, 95% CI 1.1-2.4) and heart failure (OR 1.3, 95% CI 1.0-1.7). Dutch GPs prescribe antibiotics in the majority of elderly patients with acute bronchitis and in half of the episodes of exacerbations of COPD. Tailoring their antibiotic treatment according to the presence or absence of high-risk co-morbid conditions could help GPs in improving antibiotic use in patients with respiratory tract infections in primary care.