Aortic elastic properties and cognitive function in elderly individuals: The Ikaria Study

BackgroundThe aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island.MethodsIn 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE).Results88% of the elders had normal values of MMSE score (i.e., ≥24). Elders who achieved MMSE score ≥24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg^?1 = 1.25, 95%CI 0.99–1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (>70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made.ConclusionArterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.     

Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction

BackgroundThe 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo.ObjectiveTo assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline.MethodsEnd points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb.ResultsOf 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils ≥ 150 cells/µL or FeNO ≥ 25 ppb and eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb, respectively. Similar results were observed in patient subgroups without PAO.ConclusionIn patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes.Trial Registration: ClinicalTrials.gov identifier: NCT02414854.     

Long-term neurologic and cognitive outcome and quality of life in adults after pneumococcal meningitis

ObjectivesTo perform a cross-sectional cohort study on long-term neurologic, cognitive and quality-of-life outcome in adults surviving pneumococcal meningitis.MethodsAdult survivors of community-acquired pneumococcal meningitis from a Dutch nationwide prospective cohort study were evaluated 1 to 5 years after acute illness. The control group consisted of partners or proxies of patients. Neurologic examination was performed and cognitive domains were tested with the Vienna Test System Cognitive Basic Assessment Test set (VTS COGBAT). The Research and Development (RAND)-36 and adapted Cognitive and Emotional Consequences of Stroke (CLCE)-24 questionnaires assessed perceived cognitive functioning and quality of life. Differences between group scores were tested with multivariate analyses of variance.ResultsA total of 80 pneumococcal meningitis patients and 69 controls were evaluated. After a median of 2 years (interquartile range, 2–3) after acute illness, 27 (34%) of 79 patients had persistent neurologic sequelae, most commonly hearing loss (21/79, 27%). On overall neuropsychologic evaluation, patients performed worse than the controls (MANCOVA; p 0.008), with alertness (z score −0.33, p 0.011) and cognitive flexibility (z score −0.33, p 0.027) as the most affected domains. Cognitive impairment was present in 11 (14%) of 79 patients. CLCE-24 questionnaires revealed cognitive impairment on all domains, most commonly for cognitive speed (53/75, 71%), attention (45/75, 60%) and memory (46/75, 61%). Patients had lower quality-of-life scores than controls (item physical functioning, (median) patients vs. controls, 80 vs. 95, p < 0.001; social functioning, (median) 81 vs. 100, p 0.003; perceived health, (mean) 59 vs. 70, p 0.005), which correlated with cognitive complaints (R = 0.66, p < 0.001).ConclusionsAdults after pneumococcal meningitis are at high risk of long-term neurologic and neuropsychologic deficits impairing daily life activities and quality of life.     

Quadriceps muscle compensatory activations are delayed following anterior cruciate ligament reconstruction using hamstring tendon graft

BackgroundCompensatory and anticipatory quadriceps activation (CQA and AQA) in response to postural perturbations are essential for functional stability of the knee. This study aimed at investigating CQA and AQA before and after anterior cruciate ligament reconstruction (ACLR) using hamstrings graft.MethodsTwelve participants with ACLR and 12 healthy controls were exposed to 10 either unpredictable or predictable perturbations of the knee before ACLR (T1), two months (T2) and six months (T3) after surgery. Latencies of CQA and AQA in vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM) were measured.ResultsLatency of CQA was delayed in ACLR compared to controls at T1 for VL (105 ± 25 vs. 57 ± 9 ms; P < .001), RF (102 ± 23 vs. 56 ± 9 ms; P < .001) and VM (107 ± 24 vs. 66 ± 16 ms; P < .001), at T2 for VL (68 ± 14 vs. 55 ± 10 ms; P < .01) and at T3 for VL (105 ± 22 vs. 58 ± 7 ms; P < .001), RF (102 ± 22 vs. 58 ± 12 ms; P < .001) and VM (106 ± 20 vs. 63 ± 8 ms; P < .001). AQA occurred earlier in ACLR than in controls at T1 for VL (− 82 ± 64 vs. − 14 ± 11 ms; P < .05) and VM (− 105 ± 68 vs. -9 ± 12 ms; P < .05).ConclusionCQA are delayed following ACLR with hamstring graft and should be addressd by post-surgical rehabilitation.     

Obstructive sleep apnea is associated with reduced quality of life in adult patients with asthma

BackgroundRecent data suggest that obstructive sleep apnea (OSA) is an important contributor to severe uncontrolled asthma.ObjectiveTo investigate the clinical characteristics, asthma control, and asthma-related quality of life in adult patients with asthma at a high risk for OSA.MethodsA total of 217 patients with asthma who visited our tertiary-care clinic were randomly recruited. They completed the Berlin questionnaire, which screens for OSA risk, a quality-of-life questionnaire for adult Korean patients with asthma (QLQAKA), and underwent an asthma control test (ACT). Fraction of exhaled nitric oxide (FeNO), lung function, blood lipid profiles, and body composition were evaluated.ResultsThe mean age was 58.4 ± 15.4, and 91 (41.9%) were male. Eighty-nine subjects (41.0%) were classified as high risk for OSA from the Berlin questionnaire. Patients with a high OSA risk were significantly older, had a higher prevalence of hypertension, higher BMI, non-atopic predisposition, and longer asthma treatment duration in the baseline clinical characteristics. The high OSA risk group had a lower ACT score than the low OSA risk group, but it was not statistically significant (20.9 ± 3.6 vs 21.5 ± 3.3, P = .091). The QLQAKA score was significantly lower in the high OSA risk group compared with the low OSA risk group (64.4 ± 10.9 vs 68.1 ± 11.1, P = .026), especially in the activity-domain (P = .005). The FeNO was not significantly different between the 2 groups.ConclusionQuality of life is significantly decreased in adult patients with asthma with a high risk of OSA. Special consideration is needed for the care and treatment of patients with asthma who have a high risk of OSA.     

X-linked creatine transporter deficiency results in prolonged QTc and increased sudden death risk in humans and disease model

PurposeCreatine transporter deficiency (CTD) is a rare X-linked disorder of creatine transport caused by pathogenic variants in SLC6A8 (Xq28). CTD features include developmental delay, seizures, and autism spectrum disorder. This study was designed to investigate CTD cardiac phenotype and sudden death risk.MethodsWe performed a cross-sectional analysis of CTD males between 2017 and 2020. Subjects underwent evaluation with electrocardiogram (ECG), echocardiography, and ambulatory ECG with comparable analysis in creatine transporter deficient mice (Slc6a8^−/y) using ECG, echocardiography, exercise testing, and indirect calorimetry.ResultsEighteen subjects with CTD (18 males, age 7.4 [3.8] years) were evaluated: seven subjects (39%) had QTc ≥ 470 milliseconds: 510.3 ± 29.0 vs. 448.3 ± 15.9, P < 0.0001. The QTc ≥ 470 milliseconds cohort had increased left ventricular internal dimension (diastole) ([LVIDd] Z-score: 0.22 ± 0.74, n = 7 vs. −0.93 ± 1.0, n = 11, P = 0.0059), and diminished left ventricular posterior wall dimension (diastole) ([LVPWDd, in mm]: 5.0 ± 0.6, n = 7 vs. 5.7 ± 0.8, n = 11, P = 0.0183), when compared to subjects with normal or borderline QTc prolongation. Similar ECG and echocardiographic abnormalities were seen in Slc6a8^−/y mice. Additionally, Slc6a8^−/y mice had diminished survival (65%).ConclusionProlonged QTc and abnormal echocardiographic parameters consistent with developing cardiomyopathy are seen in some male subjects with CTD. Slc6a8^−/y mice recapitulated these cardiac abnormalities. Male CTD subjects may be at increased risk for cardiac dysfunction and sudden death.     

The prognosis of highly active antiretroviral therapy (HAART) treated HIV infected patients in Serbia,related to the time of treatment initiation

BackgroundWith the introduction of highly active antiretroviral treatment (HAART) an impressive improvement in patient survival and quality of life has bee observed. However, the optimal timing of initial HAART is still under consideration.ObjectiveTo investigate the prognosis of HAART treated patients in Serbia, related to the timing of HAART initiation.Study designA series of 563 patients on HAART was retrospectively analyzed to investigate treatment response and survival.ResultsAfter a mean of 6 years (range 1–14) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 72.4%, treatment failure occurred in 7.9%, while 19.7% had a dissociative immunological/virological response. If treatment was initiated during primary HIV infection it took a shorter time to achieve a favorable response than in patients who began HAART in chronic HIV infection (2.7 ± 2.2 years vs. 6.9 ± 2.7 years, P < 0.01). A higher proportion of patients with primary HIV infection then those treated in the chronic phase achieved a favorable response to HAART (88.4% vs. 71.9%, P = 0.045). Patients who initiated HAART when their CD4 cell counts were below 200 cells/μL needed longer treatment for favorable response (8 years vs. 6 years, log rank P < 0.01). Forty-seven (8.3%) patients died. The overall estimated survival was 13 years. Patients older then 40 and IVDU were more likely to die during HAART (OR 2.6, 95% CI 1.1–5.9, P = 0.016, and OR 2.0, 95% CI 1.0–3.7, P = 0.02, respectively). However, reaching and maintaining undetectable viremia was an independent predictor of longer survival (OR 11.3, 95% CI 4.6–27.7, P < 0.01).ConclusionReaching and maintaining undetectable viremia during HAART predicted longer survival, even if sub-clinical immunodeficiency remained.     

Monitoring treatment response in chronic pulmonary aspergillosis: role of clinical,spirometric and immunological markers

ObjectivesThe treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA.MethodsWe categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response.ResultsOne hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. –3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, –0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. –62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, –2.5 ± 4.5 kg) in subjects with unfavourable response.ConclusionSerum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response.     

Trends in eczema,rhinitis, and rye grass sensitization in a longitudinal asthma cohort

BackgroundAtopic conditions are prevalent in the Western world, with limited long-term data on atopic trends in patients with asthma.ObjectiveTo describe the trends in eczema, rhinitis, and allergic sensitization in a longitudinal childhood asthma cohort.MethodsFour hundred eighty-four patients were recruited at 7 years of age and followed regularly to 50 years of age. Subjects completed an interviewer-administered questionnaire to define current eczema and rhinitis. Skin prick testing to rye grass also was performed.ResultsThe participation rate over the past 4 decades has been maintained at 72% to 91%. There was a decrease in the prevalence of eczema in the past 12 months in groups with viral-associated wheeze (21% to 8%, P = .002), asthma (47% to 18%, P < .001), and severe asthma (69% to 28%, P < .001) from 14 to 21 years of age. Conversely, there was an increase in the prevalence of rhinitis in the previous 12 months in groups without asthma (1% to 6%, P = .04; 1% to 20%, P = .008), with viral-associated wheeze (16% to 28%, P = .006; 16% to 49%, P < .001), and with asthma (45% to 56%, P = .2; 45% to 73%, P = .014) from recruitment to 10 and 14 years of age, respectively. There were 2 peaks in prevalence in the sensitization to rye grass in this cohort from 7 to 10 years of age and from 14 to 21 years of age in all groups.ConclusionThe adolescence phase appears to be an important period in the body's response to allergens whereby eczema decreases in prevalence, whereas rhinitis and rye grass sensitization increase in prevalence.     

Failure rate analysis and clinical outcomes of two different femoral tunnel positions using anteromedial portal technique in anterior cruciate ligament reconstruction

AimTo analyze two different femoral tunnel positions and to evaluate their correlation with clinical, functional outcomes and surgical revision rate in patients who underwent primary arthroscopic anterior cruciate ligament (ACL) reconstruction with anteromedial (AM) portal technique.MethodsFrom January 2015 to October 2018, we recruited 244 patients that underwent primary single-bundle ACL reconstruction, using four strand-semitendinosus graft and AM portal technique for femoral tunnel placement. Patients were divided into two groups based on the different femoral tunnel positions: 117 patients of group A had ACL footprint center femoral tunnel position compared with 127 patients of group B, with femoral tunnel placement close to the AM bundle footprint. Preoperatively and at last follow up, all patients were assessed subjectively by Lysholm, Tegner, and International Knee Documentation Committee (IKDC) scores, while Lachman, Pivot-shift, and KT-1000 tests were performed to evaluate knee joint stability.ResultsGroup B patients showed significantly better results in Lysholm, objective, and subjective IKDC scores compared with patients of group A (P < 0.001). A significantly higher surgical failure rate was found in group A than in group B (10.26% vs. 2.3%; P < 0.001). A higher anterior knee laxity was recorded in patients of group A than in patients of group B (1.9 ± 1.1 vs. 1.3 ± 1 mm; P < 0.001); a reduction in mean anterior tibial translation from preoperative to final follow up was found in group B compared with group A (3.5 ± 1.2 vs. 2.7 ± 1.1 mm; P < 0.001). No significant differences in the Tegner scale were found between the two groups.ConclusionACL reconstruction performed using the AM portal technique showed better and more satisfactory clinical and functional outcomes associated with a lower failure rate when the femoral tunnel had been placed more eccentrically in the footprint, in the AM bundle center position.     

Asthma in the elderly: risk factors and impact on physical function

BackgroundThe incidence rate of asthma has increased in all age groups in the past 40 years. Asthma in older adults is underdiagnosed and undertreated, resulting in suboptimal asthma control.ObjectiveThe objectives of the study are to evaluate differences in host characteristics between older patients with asthma and persons who do not have asthma and how these differences impact overall quality of life.MethodsPatients older than age 60 years were recruited from the general population for this case/control and nested cohort study. A complete medical history, physical examination, skin prick testing (SPT), spirometry, and exhaled nitric oxide (ENO) measurements were performed. Quality of life was assessed through the standardized SF-36v2 questionnaire. Quality of life scores, spirometry, ENO, and aeroallergen sensitization differences were compared between older patients with asthma and control patients.ResultsThe mean age of the 77 patients evaluated was 68.7 ± 7.2 years, with 59 (77%) being female. A higher rate of SPT positivity was found in patients with asthma (88.9%) compared with controls (51.2%) (P = .007). The mean percent predicted forced expiratory volume in 1 second (FEV1) at baseline was lower in the asthma group (73.7 ± 21.9%) compared with controls (89.6 ± 19.1%) (P = .007). For quality of life assessed by the SF-36v2 questionnaire, the asthma group had worse general health, increased bodily pain, and worse overall physical health compared with controls (P = .02; .021; .01).ConclusionOlder adults with asthma have a higher rate of allergic sensitization, decreased lung function, and significantly worse quality of life compared with controls.     

Clinical outcomes of medial patellofemoral ligament reconstruction using FiberTape and knotless SwiveLock anchors

BackgroundWe aimed to prospectively investigate the clinical outcomes of medial patellofemoral ligament (MPFL) reconstruction using polyester high-strength suture tape with knotless anchors.MethodForty-three patients (65 knees) were followed for at least 1 year postoperatively, with 27 patients (43 knees) followed for 2 years postoperatively. All patients underwent MPFL reconstruction using polyester high-strength suture tape (FiberTape®; Arthrex) with knotless anchors (SwiveLock®; Arthrex). Repeated dislocation and residual patellar apprehension signs were recorded, and congruence and tilting angles were measured. Changes in Knee Injury and Osteoarthritis Outcome Scale (KOOS) scores and their associations with the preoperative tibial tubercle–trochlear groove (TT-TG) distance were analyzed.ResultsNo repeat dislocations (0%) were observed. One (2.4%) residual positive patellar apprehension sign was noted. The mean tilting angle decreased from 24.8° to 10.7° (P < 0.001), and the mean congruence angle decreased from 24.9° to 4.3° (P < 0.001). At 2 years follow up, all KOOS subscales had improved: pain (92.0 ± 12.9), symptoms (90.2 ± 11.9), activities of daily living (95.7 ± 7.3), sports activity (85.7 ± 16.9), quality of life (87.7 ± 12.9), and patellofemoral (89.0 ± 9.6) outcomes. KOOS subscale scores improved regardless of the preoperative TT-TG distance (21.1 ± 3.5 mm; range, 13.8–29.9 mm).ConclusionsMPFL reconstruction using FiberTape and knotless SwiveLock anchors was performed without sacrificing autologous tissue. No recurrent patellar dislocation was observed during the 2-year follow up period. All KOOS subscale scores improved using FiberTape and SwiveLock anchors in MPFL reconstruction.     

Consumers report lower confidence in their genetics knowledge following direct-to-consumer personal genomic testing

PurposeThe aim of this study was to measure changes to genetics knowledge and self-efficacy following personal genomic testing (PGT).MethodsNew customers of 23andMe and Pathway Genomics completed a series of online surveys. We measured genetics knowledge (nine true/false items) and genetics self-efficacy (five Likert-scale items) before receipt of results and 6 months after results and used paired methods to evaluate change over time. Correlates of change (e.g., decision regret) were identified using linear regression.Results998 PGT customers (59.9% female; 85.8% White; mean age 46.9 ± 15.5 years) were included in our analyses. Mean genetics knowledge score was 8.15 ± 0.95 (out of 9) at baseline and 8.25 ± 0.92 at 6 months (P = 0.0024). Mean self-efficacy score was 29.06 ± 5.59 (out of 35) at baseline and 27.7 ± 5.46 at 6 months (P < 0.0001); on each item, 30–45% of participants reported lower self-efficacy following PGT. Change in self-efficacy was positively associated with health-care provider consultation (P = 0.0042), impact of PGT on perceived control over one’s health (P < 0.0001), and perceived value of PGT (P < 0.0001) and was negatively associated with decision regret (P < 0.0001).ConclusionLowered genetics self-efficacy following PGT may reflect an appropriate reevaluation by consumers in response to receiving complex genetic information.     

Coronary calcification in adults with Turner syndrome

PurposeAdults with Turner syndrome (TS) have an increased predisposition to ischemic heart disease. The quantitative relationship between coronary atherosclerosis and TS has yet to be established.MethodsA total of 128 females (62 with TS) participated in this prospective study. Coronary computed tomography angiography was performed to measure coronary calcified plaque burden, and prevalent noncalcified plaque burden. Regression analysis was used to study the effects of TS and traditional cardiovascular disease risk factors on coronary plaque burden.ResultsAdults with TS were 63% more likely to have coronary calcifications than controls (odds ratio 1.63, 95% confidence interval: 1.02, 2.61, P = 0.04), with an age cutoff of 51.7 years for a probability of >50% for the presence of coronary calcifications, when compared to 55.7 years in female controls. The average age of TS patients with calcified plaques was significantly lower than that of controls with calcified plaques (51.5 ± 8.9 years vs. 60.5 ± 7.0 years, P < 0.001). Age increased the likelihood of coronary calcifications by 13% per year (odds ratio 1.13, confidence interval 95%: 1.07–1.19, P < 0.001).ConclusionThis study demonstrates a higher prevalence and earlier onset of calcified coronary plaques in TS. These findings have important implications for cardiovascular risk assessment and the management of patients with TS.     

Age-related differences in asthma outcomes in the United States, 1988-2006

BackgroundRelatively little is known about the effect of age on asthma outcomes in adults, particularly at a national level.ObjectiveTo investigate age-related differences in asthma outcomes in a nationally representative, longitudinal study.MethodsWe analyzed data from the Third National Health and Nutrition Examination Survey (1988-1994) with linked mortality files through 2006. Adults with physician-diagnosed asthma were identified and were divided into 2 age groups: younger adults (17-54 years of age) and older adults (55 years or older). The outcome measures were both cross-sectional (health care use, comorbidity, and lung function) and longitudinal (all-cause mortality).ResultsThere were an estimated 9,566,000 adults with current asthma. Of these, 73% were younger adults and 27% older adults. Compared with younger adults, older adults had more hospitalizations in the past year, more comorbidities, and poorer lung function (eg, lower forced expiratory volume in 1 second) (P < .05 for all). During a median follow-up of 15 years, significant baseline predictors of higher all-cause mortality included older age (≥55 vs <55 years old: adjusted hazard ratio [HR], 6.77; 95% confidence interval [CI], 3.15-14.54), poor health status (fair and poor vs excellent health status: adjusted HR, 10.07; 95% CI, 3.75-27.01), and vitamin D deficiency (vitamin D level <30 vs ≥50 nmol/L: adjusted HR, 2.19; 95% CI, 1.05-4.58), whereas Mexican American ethnicity (adjusted HR, 0.31; 95% CI, 0.14-0.65) was associated with lower mortality. Controlling for age, asthma was not associated with increased all-cause mortality (adjusted HR, 1.28; 95% CI, 0.99-1.65).ConclusionOlder adults with asthma have a substantial burden of morbidity and increased mortality. The ethnic differences in asthma mortality and the vitamin D–mortality link merit further investigation.     

Mitochondrial DNA deletion and sarcopenia

PurposeAccumulation of mitochondrial DNA deletions and the resultant impaired oxidative phosphorylation may play a pathogenic role in the mediation of age-related sarcopenia.MethodsTwenty four participants of the New Mexico Aging Process Study were classified as normal lean (n = 15) or sarcopenic (n = 9) based on body composition determined by Dual Energy x-ray Absorptiometry. Complex I and Complex IV activities were measured in the skeletal muscle samples obtained from gastrocnemius muscle. A two-stage nested polymerase chain reaction strategy was used to identify the mitochondrial DNA deletions in the entire mitochondrial genome in the skeletal muscle samples.ResultsAlthough Complex I activity was not significantly different (5.5 ± 0.9 vs. 4.6 ± 0.7 mU/mg protein, P > 0.05), Complex IV activity was higher in sarcopenic subjects (1.4 ± 0.3 vs. 1.0 ± 0.1 mU/mg protein, P < 0.05). Mitochondrial DNA deletions were mostly located in the region of Complex I and spanned from nicotinamide adenine dinucleotide dehydrogenase 1 to nicotinamide adenine dinucleotide dehydrogenase 6. Deletions in the 8,577–10,407 bp and 10,233–11,249 bp regions were associated with a significant decrease in Complex I activity (P < 0.05 and P = 0.02, respectively). Total cumulative deletion, defined as the sum of individual length of deletions in a subject, was comparable in subjects with and without sarcopenia (1760 ± 726 vs. 1782 ± 888 bp, P > 0.05). The magnitude of mitochondrial DNA deletion, however, correlated positively with lean body mass (r = 0.43, P < 0.05).ConclusionThus, mitochondrial DNA deletions are common in elderly subjects and are negatively related to Complex I activity. The positive association between mitochondrial DNA deletions and lean body mass needs to be confirmed by studies in a larger study population.     

Changes in the characteristics of community-onset fluoroquinolone-resistant Escherichia coli isolates causing community-acquired acute pyelonephritis in South Korea

PurposeThis study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea.MethodsBlood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010–2011.ResultsA total of 300 and 346 isolates were identified in 2010–2011 and 2017–2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010–2011 and 2017–2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P < 0.001), were observed among FQ-R isolates in 2017–2018 than among those in 2010–2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P < 0.001), as well as isolates that had extended-spectrum β-lactamase (ESBL)/plasmid-mediated AmpC β-lactamase (PABL) (23.7% vs. 79.2%, P < 0.001), was observed in 2017–2018 than in 2010–2011. Further, more PMQR determinants (11.8% vs. 40.8%, P < 0.001) were observed in 2017–2018 than in 2010–2011.ConclusionsAmong uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased.     

Cuff inflation time significantly affects blood flow recorded with venous occlusion plethysmography

Purpose

We tested whether the values of limb blood flow calculated with strain-gauge venous occlusion plethysmography (VOP) differ when venous occlusion is achieved by automated, or manual inflation, so providing rapid and slower inflation, respectively.

Method

In 9 subjects (20–30 years), we calculated forearm blood flows (FBF) values at rest and following isometric handgrip at 70% maximum voluntary contraction (MVC) when rapid, or slower inflation was used.

Result

Rapid and slower cuff inflation took 0.23 ± 0.01 (mean ± SEM) and 0.92 ± 0.02 s, respectively, reflecting the range reported in published studies. At rest, FBF calculated from the 1st cardiac cycle after rapid and slower inflation gave similar values: 10.5 ± 1.4 vs. 9.6 ± 1.3 ml dl^− 1 min^− 1, respectively (P > 0.05). However, immediately post-contraction, FBF was ~ 40% lower with slower inflation: 54.6 ± 5.1 vs. 33.8 ± 4.2 ml dl^− 1 min^− 1 (P < 0.01). The latter value was similar to that calculated over the 3rd cardiac cycle following rapid inflation: 2nd cardiac cycle: 40.5 ± 4.5; 3rd cycle: 32.6 ± 4.5 ml dl^− 1 min^− 1. Regression analyses of FBFs recorded at intervals post-contraction showed those calculated over the 1st, 2nd, or 3rd cardiac cycles with rapid inflation correlated well with those from the 1st cardiac cycle with manual inflation (r = 0.79, 0.82, 0.79; P < 0.01). However, only the slope for the 3rd cycle with rapid inflation vs. slower inflation was close to unity (2.07, 1.34, and 0.94, respectively).

Conclusion

These findings confirm that the 1st cardiac cycle following venous occlusion should be used when calculating FBF using VOP and, but importantly, indicate that cuff inflation should be almost instantaneous; just ≥ 0.9 s leads to substantial underestimation, especially at high flows.

     

A behavioral intervention can decrease asthma exacerbations in older adults

BackgroundOlder adults have higher rates of asthma morbidity and mortality compared with younger age groups. Few interventions are tailored to this population.ObjectiveTo evaluate a self-management asthma intervention in older adults.MethodsAdults age 55 and older with persistent asthma were enrolled into blinded, randomized controlled trial of a 6-session asthma self-management intervention. This educational intervention was conducted in group sessions and through individual telephone calls. Outcomes including asthma exacerbations (defined as unscheduled office visits, emergency department visits, or hospitalizations for asthma), spirometric values, FeNO, asthma control, asthma quality of life, and asthma self-management were assessed at 3, 6, and 12 months.ResultsOne hundred eighty-nine subjects were enrolled, 172 were randomized and received at least 1 treatment dose, and 145 (84%) were analyzed at 12 months. On a modified intent-to-treat analysis, those in the intervention group were less likely to have an asthma exacerbation (26.9% vs 47.1%, P = .01), had a lower asthma exacerbation rate (0.8 vs 1.9, P = .02), had better asthma control (19.9 vs 18.6, P = .08), and had a higher asthma self-management score (8.9 vs 8.4, P = .03). After a mixed-model analysis to control for confounding factors, a decrease in asthma exacerbations (P = .02), as well as a decreased asthma exacerbation rate (P = .04), remained statistically significant, whereas asthma control and self-management did not. No other significant outcome differences were found.ConclusionA 6-session asthma self-management intervention can successfully decrease asthma exacerbations among older adults.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.