Reductions in functional balance, coordination, and mobility measures among patients with stable chronic obstructive pulmonary disease

PURPOSE: To compare measures of balance, coordination, and mobility between patients with chronic obstructive pulmonary disease (COPD) and healthy control subjects, and to determine whether differences in these measures are associated with measures of disease severity. METHODS: The subjects were divided into three groups: 15 patients with COPD who required the use of supplemental oxygen (WO), 15 patients with COPD who did not require the use of supplemental oxygen (NO), and 21 healthy control subjects (CO). The subjects performed spirometry and several measures of balance, coordination, and mobility including the Community Balance and Mobility Scale, the timed up and go test, the fast-gait speed test, posturography, and both a finger-to-nose test and a toe-tapping coordination test. Significance was set at an alpha less than 0.05. RESULTS: When control was used for age, significant differences were found between the WO group and the CO group for the finger-to-nose test, and for both the sway index and peak sway index for the eyes open, moving-platform test. Differences were found among all three groups for the Community Balance and Mobility Scale overall score. The scores for the WO group were significantly worse than for the NO group on the timed up and go and the fast-gait speed tests. Moderate correlation was found among all of the measures, demonstrating significant differences in forced-expiratory volume in 1 second (FEV1), peak expiratory flow, and forced-expiratory volume. When controls were used for both age and FEV1, between-group differences disappeared. CONCLUSIONS: Patients with COPD exhibit deficiencies in functional balance, coordination, and mobility tasks associated with disease severity or differences in activity levels, but not in the requirement for supplemental oxygen.     

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights

ObjectivesThe aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).BackgroundThe pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.MethodsPatients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.ResultsIn total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post–percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).ConclusionsSmoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850)     

Converting modified health assessment questionnaire (HAQ), multidimensional HAQ,and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients

Objective

The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ.

Methods

Analysis was limited to the comparison of rheumatoid arthritis (RA) patients at a random observation when the HAQ was recorded in conjunction with the MHAQ (n = 29,596), the MDHAQ (n = 13,665), or the HAQII (n = 15,823). Development models were randomly limited to 80% of the data (development sample) and the remaining 20% was used for model validation.

Results

Two conversion formulas were developed for each of the MHAQ, the MDHAQ, and the HAQII: a short model and a long model inclusive of questions common to both the modified measures and the original HAQ. Short models explained 81–83%, and long models 82–86%, of the variance. Predicted HAQ values of zero were assigned to all cases with an MDHAQ or HAQII score of zero, with remaining cases used for model estimation. Bland‐Altman plots demonstrated good concordance between actual and predicted values for each measure. The validation sample closely approximated the results from the development sample (0.005 ≤ ΔR² ≤ 0.009) for each measure.

Conclusion

We have developed and validated highly accurate conversion formulas from the MHAQ, MDHAQ, and HAQII to the original HAQ in a large sample of RA patients. The developed models are useful for conversion of measures in the research setting. Because of substantial variability at the individual patient level, application of the formulas to individual patients is inadvisable.     

Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay

This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18–64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000–December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR]?=?0.986; p?<?0.0001), male (HR?=?1.15; p?=?0.0163), diagnosed with uveitis (HR?=?1.49; p?=?0.0050), referred by primary care physicians (HR?=?1.96; p?<?0.0001), prescribed non-steroidal anti-inflammatory drugs (HR?=?1.55; p?<?0.0001), disease-modifying antirheumatic drugs (HR?=?1.33; p?<?0.0001), and tumor necrosis factor inhibitors (HR?=?1.40; p?=?0.0036), and to have had spinal/pelvic X-ray prior to referral (HR?=?1.28; p?=?0.0003). During 2000–2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate treatment.     

Immune history shapes specificity of pandemic H1N1 influenza antibody responses

Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor–binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.Most influenza pandemics occur when a new subtype of virus enters the human population. Once introduced into the human population, influenza viruses typically accumulate mutations in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, a process called antigenic drift. An H1N1 influenza virus strain caused a pandemic in 2009 (Smith et al., 2009) even though H1N1 viruses have circulated in humans from 1918 to 1957 and then again from 1977 to 2009. The 2009 pandemic H1N1 (pH1N1) strain is antigenically distinct from recently circulating seasonal H1N1 (sH1N1) strains and is more closely related to older sH1N1 strains (Garten et al., 2009; Manicassamy et al., 2010; Skountzou et al., 2010).Sera isolated from influenza-infected ferrets are currently used for surveillance of antigenically drifted influenza strains (Stöhr et al., 2012). Anti-pH1N1 antibody responses elicited in ferrets are focused on the highly variable Sa antigenic site of HA (Chen et al., 2010). Conversely, the majority of monoclonal antibodies derived from humans infected or vaccinated with pH1N1 are directed against conserved regions of the HA stalk and receptor binding domain (Li et al., 2012; O’Donnell et al., 2012; Wrammert et al., 2011). Most of these monoclonal antibodies possess many somatic mutations and bind to sH1N1 viruses efficiently, which is consistent with the idea that these antibody responses were likely originally primed by sH1N1 infection and were later recalled during pH1N1 infection/vaccination (Settembre et al., 2011; Wrammert et al., 2011; Li et al., 2012; O’Donnell et al., 2012; Qiu et al., 2012). Understanding the precise events that promote the development of these cross-reactive antibody repertoires will aid in developing a universal influenza vaccine that targets conserved areas of HA.Here, we compared the specificity of pH1N1 antibody responses elicited in different aged humans. We find that most individuals born between 1983 and 1996 elicit pH1N1 antibody responses that are dominated against an epitope near the HA receptor–binding domain. Most sH1N1 viruses that circulated between 1983 and 1996 share homology with the pH1N1 virus in this region of HA. Antibody responses dominated against this HA epitope were induced after sequential infection of ferrets with a 1991 sH1N1 virus and a pH1N1 virus. Most humans born before 1983 or after 1996 did not mount anti-pH1N1 antibody responses against this HA region. Importantly, most sH1N1 viruses that circulated before 1983 or after 1996 have an amino acid mutation or deletion in this HA epitope.     

Comparative prognostic value of myocardial strain derived from DENSE CMR: the British Heart Foundation MR-MI study

Background

Infarct size assessed early after acute ST-segment elevation myocardial infarction (STEMI) can overestimate the true extent of infarction, limiting its usefulness as a prognostic biomarker. Myocardial strain derived from displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) provides information on myocardial contractility with high precision and accuracy. We hypothesised that the prognostic value of peak circumferential strain is higher than infarct size.

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

ObjectiveElevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D.Materials and MethodsA liquid chromatography–mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention.ResultsFollowing glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P < 0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P = 0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P < 0.05).ConclusionsBCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D.     

Molecular analysis of pediatric brain tumors

The identification of molecular genetic abnormalities in specific types of pediatric brain tumors is beginning to play a role in the stratification of patients into treatment groups. The finding of an INI1 alteration in an atypical teratoid/ rhabdoid tumor or malignant neoplasm with overlapping histologic features will be required for entry onto diseasespecific protocols within the Children’s Oncology Group. Refinement in the classification of medulloblastoma and malignant glioma patients will likely depend on the genetic and signaling pathways that characterize these tumors. Advances in this area will depend on the ability to identify new disease genes, validate prognostic markers, and develop biologically based therapeutic strategies to tailor treatment.