Charity G. Moore

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

The Movement Disorder Society Task Force for Rating Scales for Parkinsons disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scales mixing of impairment and disability and its non‐linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2–4). Although a “modified HY scale” that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should “rate what you see” and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five‐point scales should be maintained.

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson's disease

The Movement Disorder Society Task Force for Rating Scales for Parkinsons disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scales mixing of impairment and disability and its non‐linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2–4). Although a “modified HY scale” that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should “rate what you see” and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five‐point scales should be maintained.

Pulmonary hypertension in patients with sickle cell disease: a longitudinal study

Although pulmonary hypertension (PHT) is a common complication in patients with sickle cell disease (SCD), the rate of development of PHT and the factors that affect disease progression are unknown. We observed 93 patients over a median follow‐up period of 2·6 years (range 0·2–5·1 years). Data were censored at the time of death or loss to follow‐up. Pulmonary hypertension was associated with an increased risk of death (relative risk, 9·24; 95% confidence interval: 1·2–73·3; P = 0·01). There was no difference in the risk of death when patients with different degrees of PHT were compared. Lactate dehydrogenase and blood urea nitrogen were significantly associated with PHT in a logistic regression model. Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were observed more frequently in patients without PHT. Thirteen per cent of patients with no previous evidence of PHT developed PHT following 3 years of observation. In conclusion: (1) PHT, regardless of severity, is associated with an increased risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD patients in their non‐crisis, steady states.

Person and Place: The Compounding Effects of Race/Ethnicity and Rurality on Health

Rural racial/ethnic minorities constitute a forgotten population. The limited research addressing rural Black, Hispanic, and American Indian/Alaska Native populations suggests that disparities in health and in health care access found among rural racial/ethnic minority populations are generally more severe than those among urban racial/ethnic minorities. We suggest that disparities must be understood as both collective and contextual phenomena. Rural racial/ethnic minority disparities in part stem from the aggregation of disadvantaged individuals in rural areas. Disparities also emerge from a context of limited educational and economic opportunity. Linking public health planning to the education and economic development sectors will reduce racial/ethnic minority disparities while increasing overall well-being in rural communities.

Prevalence and Correlates of ADHD Symptoms in the National Health Interview Survey.

Objective: Study the prevalence and correlates of ADHD symptoms in the National Health Interview Survey (NHIS). Methods: NHIS includes 10,367 children ages 4 to 17. Parents report lifetime diagnosis of ADHD and complete the Strengths and Difficulties Questionnaire (SDQ). Prevalences of clinically significant ADHD and comorbid symptoms by race and ethnicity, gender, and age are presented. Results: Prevalence of clinically significant SDQ ADHD symptoms is 4.19% (males) and 1.77% (females). Male prevalence by race is 3.06% for Hispanics, 4.33% for Whites, and 5.65% for Blacks. Significant differences in prevalence occur across gender (p < .01) and among males across race (p < .01), age (p < .01), and income (p < .02). In the full sample, 6.80% of males and 2.50% of females have a parent-reported lifetime ADHD diagnosis but are negative for SDQ ADHD. Likewise, 1.59% of males and 0.81% of females are positive for SDQ ADHD but negative for parent report of ADHD diagnosis. SDQ ADHD positive children have substantially higher proportions of elevated scores on other SDQ subscales. Conclusion: ADHD symptoms vary by race and ethnicity, gender, and age and are associated with other emotional and behavioral difficulties. Both overdiagnosis and underdiagnosis of ADHD may be issues in the U.S. population of 4- to 17-year-olds.

Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease

BACKGROUND Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume. RESULTS The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002). CONCLUSIONS In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.).

Coronary Angiography Predicts Improved Outcome Following Cardiac Arrest: Propensity-adjusted Analysis

Objectives: Determine if clinical parameters of resuscitated patients predict coronary angiography (CATH) performance and if receiving CATH after cardiac arrest is associated with outcome. Introduction: CATH is associated with survival in patients suffering out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation or ventricular tachycardia(VF/VT). Its effect on outcome in other cohorts is unknown. Methods: Chart review of resuscitated cardiac arrest patients between 2005 and 2007. Exclusion criteria: immediate withdrawal of care, hemodynamic collapse, or neurologic exam under sedation. Clinical parameters included Glasgow Coma Scale (GCS) arrest location, presenting rhythm, age, and acute ischemic ECG changes (new left bundle branch block or ST-elevation myocardial infarction-STEMI). Logistic regression identified clinical parameters predicting CATH. The association between CATH and good outcome (discharge home or to acute rehabilitation facility) was determined using logistic regression adjusting for likelihood of receiving CATH via propensity score. Result: Of the 241 patients, 96 (40%) received CATH. Significant disease (≥70% stenosis) of ≥1 coronary arteries was identified in 69% of patients including 57% of patients without acute ischemic ECG changes. Unadjusted predictors of CATH were sex, method of arrival, OHCA, presenting rhythm, acute ischemic ECG changes, and GCS. Propensity adjusted logistic regression demonstrated an association between CATH and good outcome (OR 2.16; 95% CI 1.12, 4.19; P < 0.02). Conclusion: CATH is more likely to be performed in certain patients and identifies a significant number of high-grade stenoses in this population. Receiving CATH was independently associated with good outcome.

Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension.

Patients with sickle cell disease-associated pulmonary hypertension have increased endothelial dysfunction, coagulation activation and inflammation compared with patients without pulmonary hypertension. Endothelial dysfunction and coagulation activation appear to be the result of chronic hemolysis. See related perspective on page 1. Background Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD. Design and Methods This cross-sectional study was performed using a cohort of patients followed at an adult Sickle Cell Clinic. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age, sex and body mass index-adjusted reference ranges. Clinical laboratory examinations, including hematologic studies and biochemical tests, as well as various measures of coagulation activation, endothelial activation and inflammation, were conducted on SCD subjects and on healthy, race-matched control subjects without SCD. Results Patients with SCD (n=76) had higher plasma levels of markers of coagulation (thrombin-antithrombin complex, prothrombin fragment F1+2, D-dimer) and endothelial (soluble vascular endothelial cell adhesion molecule, sVCAM) activation compared with control subjects (n=6). SCD patients with PHT (n=26) had significantly higher levels of sVCAM compared with those patients without PHT (n=50). Although PHT patients showed increased plasma measures of coagulation activation, the differences were not statistically significant when compared to those of patients without PHT. HbSS patients with PHT also had a trend towards higher levels of other inflammatory cytokines (interleukins 6, 8 and 10) than HbSS patients without PHT. There was a modest negative correlation between hemoglobin and plasma measures of coagulation and endothelial activation, and modest positive correlations between markers of hemolysis and plasma measures of coagulation and endothelial activation. Conclusions SCD patients with PHT have higher levels of markers of endothelial activation and other inflammatory markers than patients without PHT. A trend towards an increased level of markers of coagulation activation was observed in SCD patients with PHT compared with that in patients without PHT. Markers of hemolysis are associated with coagulation activation and endothelial dysfunction in SCD patients. Clinical trials of anticoagulants and anti-inflammatory agents are warranted in SCD patients with PHT.

Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease

BACKGROUND Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB). METHODS In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years. RESULTS There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups. CONCLUSIONS Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).

Recommendations for Planning Pilot Studies in Clinical and Translational Research

Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337