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International audience; Background In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. Methods We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. Results The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83-1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). Conclusion The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.

Background and Aim Liver histology changes are the current gold standard for evaluating non‐alcoholic steatohepatitis (NASH), but are limited by their invasiveness and variability for sampling and interpretation. We evaluated noninvasive biomarkers as an indication of histologic changes in NASH. Methods Associations between 12‐month biomarker and NASH Clinical Research Network histologic score changes in 339 patients with NASH in the EMMINENCE trial was examined with multivariable models and partial canonical correlation. A meta‐analysis of 17 NASH trials including 3717 patients examined associations between these same changes and histologic response within treatment groups, and treatment effects on biomarkers and on liver histology. Biopsy measures assessed were changes in ballooning, steatosis, inflammation, and fibrosis, NASH improvement without worsening of fibrosis, and fibrosis improvement without worsening of NASH. All analytic methods suggest that a combination of aspartate aminotransferase (AST), cytokeratin‐18 (CK‐18 [M30 or M65]), and hemoglobin A1C (HbA1c) changes best predicts overall liver biopsy changes in response to interventions. Results The weighted average of standardized mean changes (0.403 × AST, 0.314 × CK‐18, 0.283 × HbA1c) facilitated comparisons of within‐group responses and treatment effects among studies included in the meta‐analysis. This composite in EMMINENCE discriminated between patients with and without NASH resolution without worsening fibrosis with area under the receiver‐operator characteristic curve of 0.7880, and for fibrosis improvement without NASH worsening of 0.7553. Conclusion A composite score based on changes in AST, HbA1c, and CK‐18 could serve as a surrogate for liver histologic improvement and an effective objective, noninvasive tool for comparative assessment of treatment effects of novel interventions., Liver histology changes are the current gold standard for evaluating treatments for non‐alcoholic steatohepatitis (NASH), but are limited by their invasiveness and variability for sampling and interpretation. We evaluated noninvasive biomarkers as an indication of histologic changes in NASH. A composite score based on changes in AST, HbA1c, and CK‐18 could serve as a surrogate for liver histologic improvement and an effective objective, noninvasive tool for comparative assessment of treatment effects of novel interventions.

Background & Aims Liver biopsies are a critical component of pivotal studies in non-alcoholic steatohepatitis (NASH), constituting inclusion criteria, risk stratification factors and endpoints. We evaluated the reliability of NASH Clinical Research Network scoring of liver biopsies in a NASH clinical trial. Methods Digitized slides of 678 biopsies from 339 patients with paired biopsies randomized into the EMMINENCE study – examining a novel insulin sensitizer (MSDC-0602K) in NASH – were read independently by 3 hepatopathologists blinded to treatment code and scored using the NASH CRN histological scoring system. Various endpoints were computed from these scores. Results Inter-reader linearly weighted kappas were 0.609, 0.484, 0.328, and 0.517 for steatosis, fibrosis, lobular inflammation, and ballooning, respectively. Inter-reader unweighted kappas were 0.400 for the diagnosis of NASH, 0.396 for NASH resolution without worsening fibrosis, and 0.366 for fibrosis improvement without worsening NASH. In the current study, 46.3% of the patients included in the study based on 1 hepatopathologist's qualifying reading were deemed not to meet the study's histologic inclusion criteria by at least 1 of the 3 hepatopathologists. The MSDC-0602K treatment effect was lowest for those histologic features with lower inter-reader reliability. Simulations show that the lack of reliability of endpoints and inclusion criteria can drastically reduce study power – from >90% in a well-powered study to as low as 40%. Conclusions The reliability of hepatopathologists' liver biopsy evaluation using currently accepted criteria is suboptimal. This lack of reliability may affect NASH pivotal studies by introducing patients who do not meet NASH study entry criteria, misclassifying fibrosis subgroups, and attenuating apparent treatment effects. Lay summary Since liver biopsy analysis plays such an important role in clinical studies of non-alcoholic steatohepatitis, it is important to understand the reliability of hepato-pathologist readings. We examined both inter- and intra-reader variability in a large data set of paired liver biopsies from a clinical trial. We found very poor inter-reader and modest intra-reader variability. This result has important implications for entry criteria, fibrosis stratification, and the ability to measure a treatment effect in clinical trials.

Aims The relationship between N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) and galectin‐3 and outcomes has not been studied in African patients with acute heart failure (AHF). The current analysis sought to describe the association between plasma levels of NT‐pro‐BNP and galectin‐3 and cardiovascular (CV) death or heart failure (HF) hospitalization, as well as their associations with symptoms and echocardiography markers of left and right ventricular remodelling among AHF patientsv in sub‐Saharan Africa. Methods and results In a subset of 80 patients with complete data in a study assessing the effects of hydralazine and nitrates in patients with AHF (BAHEF trial; NCT01822808), NT‐pro‐BNP and galectin‐3 analyses were performed, and the association with various characteristics and outcome measures assessed. The mean age of the patients for whom the aforementioned biomarkers were measured was 52.6 years, with 52.5% women. Galectin‐3 at baseline predicted changes (Week 24 to baseline) in left ventricular ejection fraction, left ventricular end‐systolic diameter, left ventricular end‐diastolic diameter, and tricuspid annular plane systolic excursion. Biomarkers and their changes were not associated with changes in 6 min walk test at 24 weeks. Baseline galectin‐3 and change in NT‐pro‐BNP were associated with improvements in dyspnoea at 24 weeks. Nine patients had an HF readmission or died of CV causes through 24 weeks (11.6%). Both biomarkers at baseline predicted combined CV death or HF hospitalization through Week 24 (P‐values = 0.0328 and 0.0001, respectively). Conclusions In a cohort of patients with AHF from sub‐Saharan Africa, NT‐pro‐BNP and galectin‐3 at baseline and their changes were associated with some changes in dyspnoea, echocardiographic remodelling, and CV death or HF hospitalization through Week 24. These tests have potential of being used for risk stratification of AHF patients in sub‐Saharan Africa where resources are scarce.

International audience; Aims: Over the last 30 years, many medicine development programmes in acute and chronic heart failure (HF) with preserved ejection fraction (HFpEF) have failed, in contrast to those in HF with reduced ejection fraction (HFrEF). We explore how the neutral results in larger HF trials may be attributable to chance and/or the dilution of statistical power.Methods and results: Using simulations, we examined the probability that a positive finding in a Phase 2 trial would result in the study of a truly effective medicine in a Phase 3 trial. We assessed the similarity of clinical trial and registry patient populations. We conducted a meta-analysis of paired Phase 2 and 3 trials in HFrEF and acute HF examining the associations of trial phase and size with placebo event rates and treatment effects for HF events and death. We estimated loss in trial power attributable to dilution with increasing trial size. Appropriately powered Phase 3 trials should have yielded ∼35% positive results. Patient populations in Phase 3 trials are similar to those in Phase 2 trials but both differ substantially from the populations of 'real-life' registries. We observed decreasing placebo event rates and smaller treatment effects with increasing trial size, especially for HF events (and less so for mortality). This was more pronounced in trials in acute HF patients.Conclusions: The selection of more positive Phase 2 trials for further development does not explain the failure of HFpEF and acute HF medicine development. Increasing sample size may lead to reduced event rates and smaller treatment effects, resulting in a high rate of neutral Phase 3 trials.

Background & Aims MSDC-0602K is a novel insulin sensitizer designed to preferentially target the mitochondrial pyruvate carrier while minimizing direct binding to the transcriptional factor PPARγ. Herein, we aimed to assess the efficacy and safety of MSDC-0602K in patients with non-alcoholic steatohepatitis. Methods Patients with biopsy-confirmed NASH and fibrosis (F1-F3) were randomized to daily oral placebo, or 1 of 3 MSDC-0602K doses in a 52-week double-blind study. The primary efficacy endpoint was hepatic histological improvement of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) with a ≥1-point reduction in either ballooning or lobular inflammation and no increase in fibrosis stage at 12 months. Secondary endpoints included NAS improvement without worsening fibrosis, NASH resolution, and fibrosis reduction. Exploratory endpoints included changes in insulin sensitivity, liver injury and liver fibrosis markers. Results Patients were randomly assigned to placebo (n = 94), or 62.5 mg (n = 99), 125 mg (n = 98), or 250 mg (n = 101) of MSDC-0602K. At baseline, glycated hemoglobin was 6.4 ± 1.0%, 61.5% of patients had fibrosis F2/F3 and the average NAS was 5.3. The primary endpoint was reached in 29.7%, 29.8%, 32.9% and 39.5% of patients in the placebo, 62.5 mg, 125 mg and 250 mg dose arms, respectively, with adjusted odds ratios relative to placebo of 0.89 (95% CI 0.44–1.81), 1.22 (95% CI 0.60–2.48), and 1.64 (95% CI 0.83–3.27). The 2 highest doses of MSDC-0602K led to significant reductions in glucose, glycated hemoglobin, insulin, liver enzymes and NAS compared to placebo. The incidence of hypoglycemia and PPARγ-agonist-associated events such as edema and fractures were similar in the placebo and MSDC-0602K groups. Conclusions MSDC-0602K did not demonstrate statistically significant effects on primary and secondary liver histology endpoints. However, effects on non-invasive measures of liver cell injury and glucose metabolism support further exploration of MSDC-0602K's safety and potential efficacy in patients with type 2 diabetes and liver injury. [ClinicalTrials.gov Identifier: NCT02784444]. Lay summary First-generation insulin sensitizers are used to treat type 2 diabetes, but are associated with side effects including edema, bone fractures, and hypoglycemia. MSDC-0602K is a second-generation insulin sensitizer designed to reduce these side effects. We hypothesized that insulin sensitization could improve non-alcoholic steatohepatitis. In the current study of patients with non-alcoholic steatohepatitis, MSDC-0602K did not demonstrate significant effects on liver histology with the biopsy techniques used. However, useful information was gained for the design of future studies and MSDC-0602K significantly decreased fasting glucose, insulin, glycated hemoglobin, and markers of liver injury without dose-limiting side effects.

BACKGROUND: Rheumatic heart disease (RHD) was found in the THESUS-HF registry to be the third most common cause of acute heart failure (AHF) in Sub-Saharan Africa. METHODS: One thousand six patients with AHF from 9 Sub-Saharan African countries were recruited in THESUS-HF, of which 143 (14.3%) had RHD-AHF. Clinical characteristics and outcomes in patients with RHD-AHF and non-RHD-AHF were compared. Kaplan-Meier plots for time to all-cause death and/or HF readmission according to the presence of RHD-AHF and non-RHD-AHF were performed and survival distributions compared using the log-rank test. Cox regression was used to determine the hazard ratio of death to day 180 and death or readmission to day 60 after adjusting for confounders. RESULTS: Patients with RHD-AHF were younger, more often females, had higher rates of atrial fibrillation, had less hypertension, hyperlipidemia and diabetes, had lower BP, and higher pulse rate and better kidney function and echocardiographic higher ejection fraction larger left atria and more diastolic dysfunction. Patients with RHD-AHF had a numerically longer mean stay in the hospital (10.5 vs. 8.8 days) and significantly higher initial hospitalization mortality (9.1% vs. 3.4%). CONCLUSIONS: In conclusion, patients with HF related to RHD were younger, have higher rate of atrial fibrillation and have a worse short-term outcome compared to HF related to other etiologies in Sub-Saharan Africa.

International audience; No abstract available

Aims: \ud This retrospective analysis sought to identify markers that might distinguish between acute heart failure (HF) and worsening HF in chronic outpatients.\ud \ud Methods and Results: \ud The BIOSTAT‐CHF index cohort included 2516 patients with new or worsening HF symptoms: 1694 enrolled as inpatients (acute HF) and 822 as outpatients (worsening HF in chronic outpatients). A validation cohort included 935 inpatients and 803 outpatients. Multivariable models were developed in the index cohort using clinical characteristics, routine laboratory values, and proteomics data to examine which factors predict adverse outcomes in both conditions and to determine which factors differ between acute HF and worsening HF in chronic outpatients, validated in the validation cohort.\ud \ud Patients with acute HF had substantially higher morbidity and mortality (6 months mortality was 12..3% for acute HF and 4..7% for worsening HF in chronic outpatients). Multivariable models predicting 180‐day mortality and 180‐day HF re‐admission differed substantially between acute HF and worsening HF in chronic outpatients. CA‐125 was the strongest single biomarker to distinguish acute HF from worsening HF in chronic outpatients, but only yielded a C‐index of 0..71. A model including multiple biomarkers and clinical variables achieved a high degree of discrimination with a C‐index of 0..913 in the index cohort and 0..901 in the validation cohort.\ud \ud Conclusion: \ud The study identifies different characteristics and predictors of outcome in acute HF patients as compared to outpatients with chronic HF developing worsening HF. The markers identified may be useful in better diagnosing acute HF and may become targets for treatment development.

Aims Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients.

Aims Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study. Methods and results Patients (n=351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF

Objective We evaluated the effects of menstrual types inclusive of PMS on reports of chronic pain intensity and psychopathology in twenty-eight women (mean age 38.93 ± 13.51) with Sickle Cell disease (SCD). Methods Using the Menstrual Symptoms Questionnaire, we compared women with PMS to those with less distressing spasmodic cycle types. Results Thirty-four percent of the sample used oral contraception; there were no significant effects of birth control use on reports of pain. Women with PMS characterized the sensory (p = .04) and affective (p = .04) experiences of their SCD-related chronic pain, including their current pain intensity (p = .03), as significantly greater than women with primary spasmodic menstrual type. Further, there was a trend towards significance for women with PMS to report greater levels of overall pain intensity (p = .07) and average pain intensity over the past month (p = .08). Conclusions The authors interpret these results to suggest that there may be a complex interaction of neurohormonal, biological, and psychological factors associated with PMS that influence manifestation and experience of chronic pain in patients with SCD.

AimsThe course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled in the PROTECT study. Methods and resultsPROTECT was a randomized study that examined the effect of the adenosine blocker rolofylline in patients within 24h of admission for AHF with mild to moderate renal impairment. Geographic-region-adjusted multivariable models showed that LOS was only partly explained by the severity of heart failure (HF), comorbidities (diabetes mellitus, renal impairment, ischaemic heart disease) and degree of metabolic dysfunction (cholesterol and albumin) at baseline (adjusted R-2 0.27). Addition of in-hospital worsening heart failure (WHF) and changes in metabolic markers contributed significantly to prediction of LOS [R-2 difference 0.050, 95% confidence interval (CI) 0.0282-0.072]. Thirty-day HF readmission was associated with more severe HF and previous HF admission but not with LOS (odds ratios 1.00, 95% CI 0.97-1.04). Death within 90days after discharge was associated with older age, more severe HF, worse renal function, and lower sodium and bicarbonate at admission; LOS was a strong predictor of 90-day post-discharge mortality. ConclusionsIn patients admitted for AHF, LOS is not well-predicted by traditional markers of disease severity, but strongly associated with the occurrence of in-hospital WHF. Longer LOS is a strong predictor of early mortality after discharge but not of readmission. These findings may help focus efforts to reduce LOS and post-discharge outcomes on patients' subgroups at increased risk.

Background: The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. Methods and Results: In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29–5.73) more days ( P =0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06–2.09) times higher ( P =0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. Conclusions: In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment. Clinical Trial Registration : URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00328692 and NCT00354458.

Objectives These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF). Background WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF. Methods Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis. Results Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-index = 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all p Conclusions WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death.

Cognitive-behavioral models for both insomnia and pain are well established. Few studies have addressed the cognitive-behavioral aspects of these conditions occurring together with a unified model. Worry, rumination, catastrophizing, monitoring, misperceptions, dysfunctional beliefs, and safety behaviors are reviewed. Sleep hygiene among those with co-occurring pain and insomnia is also discussed. It is proposed that more concerted efforts are needed to develop an integrated cognitive-behavioral model to address insomnia and pain as a complex integrated phenomenon.

Summary Background: The role of echocardiography in the risk stratification of acute heart failure (HF) is unknown. Some small studies and retrospective analyses have found little change in echocardiographic variables during admission for acute HF and some echocardiographic parameters were not found to be associated with outcomes. It is unknown which echocardiographic variables will predict outcomes in sub-Saharan African patients admitted with acute HF. Using echocardiograms, this study aimed to determine the predictors of death and re-admissions within 60 days and deaths up to 180 days in patients with acute heart failure. Methods: Out of the 1 006 patients in the THESUS-HF registry, 954 had had an echocardiogram performed within a few weeks of admission. Echocardiographic measurements were performed according to the American Society of Echocardiography guidelines. We examined the associations between each echocardiographic predictor and outcome using regression models. Results: Heart rate and left atrial size predicted death within 60 days or re-admission. Heart rate, left ventricular posterior wall thickness in diastole (PWTd), and presence of aortic stenosis were associated with the risk of death within 180 days. PTWd added to clinical variables in predicting 180-day mortality rates. Conclusions: Echocardiographic variables, especially those of left ventricular size and function, were not found to have additional predictive value in patients admitted for acute HF. Left atrial size, aortic stenosis, heart rate and measures of hypertrophy (LV PWTd) had some predictive value, suggesting the importance of early treatment of hypertension and severe valvular heart disease.

Co-occurring chronic pain and insomnia are common in a clinical setting. Cognitive–behavioral theoretical (CBT) frameworks exist for both conditions independently. The purpose of this study was to address the problem of co-occurring chronic pain and insomnia with an integrated CBT model based on empirical support. One-hundred eleven individuals (age range 21–65 years) meeting the general criteria for chronic pain and insomnia were included in this study. Participants completed a demographic form, the Dysfunctional Beliefs and Attitudes about Sleep—16-item version, Insomnia Severity Index, Sleep Hygiene Index, Sleep Associated Monitoring Index, Pain Catastrophizing Scale, Pain Disability Questionnaire, Modified Somatic Perceptions Questionnaire, Hospital Anxiety and Depression Scale, and Multidimensional Scale of Perceived Social Support. Significant positive bivariate relationships were observed for pain catastrophizing (PC) and dysfunctional beliefs and attitudes about sleep (DBAS), as well as somatic awareness and sleep-associated monitoring. Two backward stepwise regression models were utilized to determine a model for predicting insomnia severity and pain disability respectively using a combination of sleep and pain-associated measures. Insomnia severity was predicted by DBAS, PC, and somatic awareness. Pain disability was predicted by PC, DBAS, depression, and social support. Maladaptive thought patterns related to pain and insomnia and associated features appear to have a synergistic effect on both insomnia severity and pain disability and support a combined cognitive–behavioral model.

Aims In Western countries with typically elderly ischaemic acute heart failure patients, predictors and clinical outcome of renal dysfunction and worsening renal function are well described. However, the prevalence, predictors and clinical outcome of renal dysfunction in younger, mainly hypertensive acute heart failure patients from Africa, have not been described. Methods and results From 1006 patients enrolled in the sub-Saharan Africa Survey of Heart Failure (THESUS-HF), renal function was determined by the estimated glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) formula. Worsening renal function was defined as an increase in creatinine ≤0.3 mg/dL (26.5 µmol/L) from baseline to day 7/discharge. The mean (SD) age of the patients was 52.4 (18.2) years, 481 (50.8%) were women and the predominant race was black African [932 of 946 (98.5%)]. Heart failure was most commonly a result of hypertension (n = 363, 39.5%) and only 7.8% had ischaemic heart failure. At hospital admission, 289 patients (30.6%) had an estimated glomerular filtration rate ≤60 ml/min.1.73m2. Worsening renal function during hospitalization was detected in 53 (9.8 %) of 543 patients with a follow-up creatinine value, and was independently associated with the Western sub-Saharan region, body mass index, and the presence of rales. Worsening renal function was an independent predictor of death or readmission over 60 days [multivariable hazard ratio = 2.06 (1.10, 3.38); P = 0.023] and all-cause death over 180 days [multivariable hazard ratio =1.92 (1.08, 3.38); P = 0.025]. Conclusions Renal dysfunction is also prevalent in younger non-ischaemic acute heart failure patients in Africa, but worsening renal function is less prevalent and has different predictors compared with Western cohorts. Nevertheless, worsening renal function is strongly and independently related with clinical outcome.

Aims Contrary to elderly patients with ischaemic-related acute heart failure (AHF) typically enrolled in North American and European registries, patients enrolled in the sub-Saharan Africa Survey of Heart Failure (THESUS-HF) were middle-aged with AHF due primarily to non-ischaemic causes. We sought to describe factors prognostic of re-admission and death in this developing population. Methods and results Prognostic models were developed from data collected on 1006 patients enrolled in THESUS-HF, a prospective registry of AHF patients in 12 hospitals in nine sub-Saharan African countries, mostly in Nigeria, Uganda, and South Africa. The main predictors of 60-day re-admission or death in a model excluding the geographic region were a history of malignancy and severe lung disease, admission systolic blood pressure, heart rate and signs of congestion (rales), kidney function (BUN), and echocardiographic ejection fraction. In a model including region, the Southern region had a higher risk. Age and admission sodium levels were not prognostic. Predictors of 180-day mortality included malignancy, severe lung disease, smoking history, systolic blood pressure, heart rate, and symptoms and signs of congestion (orthopnoea, peripheral oedema and rales) at admission, kidney dysfunction (BUN), anaemia, and HIV positivity. Discrimination was low for all models, similar to models for European and North American patients, suggesting that the main factors contributing to adverse outcomes are still unknown. Conclusion Despite the differences in age and disease characteristics, the main predictors for 6 months mortality and combined 60 days re-admission and death are largely similar in sub-Saharan Africa as in the rest of the world, with some exceptions such as the association of the HIV status with mortality.

Objectives The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure. Background Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage. Methods The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies. Results Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro–brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion. Conclusions Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.

Background: \ud \ud The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs.\ud \ud Methods and Results: \ud \ud We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P

Introduction: Rheumatic heart disease (RHD) is the commonest cause of valvular heart disease and a common cause of heart failure in sub-Saharan Africa (SSA). Atrial fibrillation (AF) complicates RHD, precipitates and worsens heart failure and cause unfavourable outcomes. We set out to describe the prevalence, clinical characteristics and outcomes of valvular atrial fibrillation in a cohort of African patients with acute heart failure (AHF). Methods: The sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective, observational survey of AHF in nine countries. We collected demographic data, medical history and signs and symptoms of HF. Electrocardiograms (ECGs) were done in a standard fashion. AF was defined as either a history of AF or AF on the admission ECG. Using Cox regression models, we examined the associations of AF with all-cause death over 180 days and a composite endpoint of all-cause death or readmission over 60 days. Results: There were 1 006 patients in the registry. The mean age was 52.3 years and 50.8% were women. AF was present in 209 (20.8%) cases. Those with AF were older (57.1 vs 51.1 years), more likely to be female (57.4 vs 49.1%), had significantly lower systolic (125 vs 132 mmHg) and diastolic (81 vs 85 mmHg) blood pressure (BP), and higher heart rates (109 vs 102 bpm). Ninety-two (44%) AF patients had valvular heart disease. The presence of AF was not associated with the primary endpoints, but having valvular AF predicted death within 180 days. Conclusion: AF was present in one-fifth of African patients with AHF. Almost half of the AF patients had valvular disease (RHD) and were significantly younger and at risk of dying within six months. It is important to identify these high-risk patients and prioritise their management, especially in SSA where resources are limited.

Aims Patients with acute heart failure in Africa are rarely being treated with a hydralazine/nitrates combination. Therefore the effect of this treatment was studied here Methods and results The study was planned to enrol 500 patients during an acute heart failure (HF) admission, from nine sub-Saharan African countries. Patients were randomized in a double-blind manner to receive 50 mg hydralazine/20 mg isosorbide dinitrate (HYIS) t.i.d. or matching placebo for 24 weeks followed by open label HYIS for all patients. The study was terminated after 147 patients were enrolled due mostly to issues with recruitment into a prospective, placebo-controlled study. Most patients were recruited from Mozambique, South Africa, Kenya, and Uganda. The primary endpoint of death or HF readmission through 24 weeks was neutral [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.48–2.27, P = 0.90] in the 133 randomized patients included in the analyses. There were non-signficant effects in favour of HYIS in secondary endpoints including change in dyspnoea severity at day 7 or discharge, decrease in systolic blood pressure, greater decrease in weight, and increase in 6-min walk test distance at week 24. There were also small changes in echocardiographic indices of cardiac size and function in favour or HYIS, but none was significant. Conclusion The BA-HEF trial demonstrated challenges in recruiting the expected number of patients with acute HF in a number of African countries, which highlights the need for strategic logistic support. Trial registration: NCT01822808.

Purpose: To determine the genetic and environmental influences exerted on arthritis by measuring the distribution of self-reported arthritis diagnoses among monozygotic (MZ) and dizygotic (DZ) African American twins. Methods: A cross-sectional study was conducted on 97 MZ and 113 DZ twin pairs recruited into the Carolina African American Twin Study of Aging (CAATSA). The sample had a mean age of 47 ± 13.9 years. A twin design was used to determine correlations in arthritis diagnosis for MZ and DZ twins and to estimate the contribution of genes and environment to the variation in an arthritis diagnosis. Results: The concordance rate for being diagnosed with arthritis was 42% for MZ twins, and 20% for DZ twins, resulting in a 2.1:1 ratio of MZ to DZ concordance. These results indicate a significant proportion of individual variability was due to genetic factors (43%) on an arthritis diagnosis as well as 57% of variance due to nonshared environmental influences. Conclusions: This research suggests that while there are genetic influences on arthritis diagnosis, environmental factors, such as infections, dietary factors, urbanization, and pollutants, also play a role in accounting for variability in the diagnosis and treatment of arthritis among diverse populations.

Healthcare disparities are a growing area of interest among scientists and clinicians. Articles identified from searches of the PubMed and PsycInfo databases, as well as the Google Scholar search engine including combinations of the key words and phrases: Black men, circadian rhythm, disease, ethnicity, gender, health disparities, illness, insomnia, race, sleep, sleep apnea, and sleep disorders were used for this review. This brief review addresses some of the limited work on sleep among Black men. Some information is available regarding expected sleep parameters, insomnia, sleep-disordered breathing, and sleep disturbances related to general medical conditions. Many areas are still in need of exploration and, although emphasizing aspects of sleep, the present work is intended as a foundation to encourage further exploration across many disciplines in the health sciences.

Introduction: The psychological influence of food (PFS) and perceived barriers to lifestyle change (PBLC) were considered as predictors of body mass index and website tool utilization (TU) in an online weight loss program. Materials and Methodology: An archival analysis of all (N = 1361) overweight/obese (BMI M = 31.6 + 6.24 kg/m2), adult (M = 42.0 + 10.72 years) users (82.4% female) of an evidence-based, multidisciplinary Internet weight loss program was performed. Predictor variables included: PFS and PBLC, age, and longest maintained weight loss in relation to 1) BMI 2) TU. Results: Both PBLC and PFS were correlated with baseline BMI and TU. Regression analyses indicated that only PFS independently predicted BMI (p = .0001) and TU (p = .001) when the model included all predictor variables. One-way ANOVA indicated gender differences on both PBLC and PFS scores (p = .001). Subsequent regression analyses separated by gender showed that in females PFS predicted BMI (p = .0001) and TU (p = .005). For males no variable significantly predicted BMI (p’s > .05) however PBLC did predict TU (p = .008). Conclusions: Our findings suggest that when developing online weight loss programs clinical characteristics of the user could inform website algorithms to maximize website utilization. Gender differences indicated that for women it may be important to understand how factors related to the psychological influence of food impact utilization of online weight loss programs, however, for men broader barriers to lifestyle change is an important consideration.

Background— Worsening renal function (WRF), traditionally defined as an increase in serum creatinine levels ≥0.3 mg/dL, is a frequent finding in patients with acute heart failure (AHF) and has been associated with poorer outcomes in some but not all studies. We hypothesized that these discrepancies may be caused by the interaction between WRF and congestion in AHF patients. Methods and Results— We measured serum creatinine levels on a daily basis during the hospitalization and assessed the persistence of signs of congestion at discharge in 599 consecutive patients admitted at our institute for AHF. They had a postdischarge mortality and mortality or AHF readmission rates of 13% and 43%, respectively, after 1 year. Patients were subdivided into 4 groups according to the development or not of WRF and the persistence of ≥1 sign of congestion at discharge. Patients with WRF and no congestion had similar outcomes compared with those with no WRF and no congestion, whereas the risk of death or of death or AHF readmission was increased in the patients with persistent congestion alone and in those with both WRF and congestion (hazard ratio, 5.35; 95% confidence interval, 3.0–9.55 at univariable analysis; hazard ratio, 2.44; 95% confidence interval, 1.24–4.18 at multivariable analysis for mortality; hazard ratio, 2.14; 95% confidence interval, 1.39–3.3 at univariable analysis; and hazard ratio, 1.39; 95% confidence interval, 0.88–2.2 at multivariable analysis for mortality and rehospitalizations). Conclusions— WRF alone, when detected using serial serum creatinine measurements, is not an independent determinant of outcomes in patients with AHF. It has an additive prognostic value when it occurs in patients with persistent signs of congestion.

Background Symptoms and signs of heart failure (HF) are the most common reasons for admission to hospital for acute HF (AHF) and are used routinely throughout admission to assess the severity of disease and response to therapy. Methods and Results The data were collected in The Sub-Saharan Africa Survey on Heart Failure (THESUS-HF) study, a prospective, multicenter, observational survey of AHF from 9 countries in sub-Saharan Africa. A total of 1006 patients, ≥12 years of age, hospitalized for AHF were recruited. Symptoms and signs of HF and changes in dyspnea and well-being, relative to admission, were assessed at entry and on days 1, 2, and 7 (or on discharge if earlier) and included oxygen saturation, degree of edema and rales, body weight, and level of orthopnea. The patient determined dyspnea and general well-being, whereas the physician determined symptoms and signs of HF, as well as improvements in vital sign measurement, throughout the admission. After multivariable adjustment, baseline rales and changes to day 7 or discharge in general well-being predicted death or HF hospitalization through day 60, and baseline orthopnea, edema, rales, oxygen saturation, and changes to day 7 or on discharge in respiratory rate and general well-being were predictive of death through day 180. Conclusions In AHF patients in sub-Saharan Africa, symptoms and signs of HF improve throughout admission, and simple assessments, including edema, rales, oxygen saturation, respiratory rate, and asking the patient about general well-being, are valuable tools in patients' clinical assessment.

Objective We evaluated the effect of perceived discrimination, optimism, and their interaction on health care utilization among African American adults with sickle cell disease(SCD). Methods Measures of optimism and perceived discrimination were obtained in 49 African American SCD patients. Multiple regression analyses controlling for sex and age tested effects of optimism and perceived discrimination on the number of emergency department visits (ED) and number and duration of hospitalizations over the past year. Results A perceived discrimination-optimism interaction was associated with number of emergency departments visits (b = .29, p = .052), number of hospitalizations (b = .36, p = .019), and duration of hospitalizations (b = .30, p = .045) such that those with high perceived discrimination/high optimism had the greatest health care utilization. Conclusions African American SCD patients with high perceived discrimination/high optimism had greater health care utilization than patients who reported either low perceived discrimination or low optimism. This study suggests that patient personality and coping styles should be considered when evaluating the effects of stress on SCD-related outcomes.

Obesity is a biological risk factor or comorbidity that has not received much attention from scientists studying hypertension among African American men. The purpose of this study was to examine the relationship between weight status and high blood pressure among African American men with few economic resources. The authors used surveillance data collected from low-income adults attending community- and faith-based primary care clinics in West Tennessee to estimate pooled and group-specific regression models of high blood pressure. The results from group-specific logistic regression models indicate that the factors associated with hypertension varied considerably by weight status. This study provides a glimpse into the complex relationship between weight status and high blood pressure status among African American men. Additional research is needed to identify mechanisms through which excess weight affects the development and progression of high blood pressure.

Objective: The present paper examines the literature that addresses psychologic aspects involved in complex regional pain syndrome from a historic perspective to provide a rationale for the emergence of psychologic theories to explain its pathogenesis. The support of such perspective is then analyzed through the review of evidencebased studies. Methods: A review of the literature from a historic perspective was presented since its first description to the present time, including the clinical presentation and associated symptoms. An evidence-based approach was used to review the literature on complex regional pain syndrome and psychologic factors associated with the etiology or as predictors in the development of the disorder. Results: After reviewing the literature on the history and the myths associated with complex regional pain syndrome, a hypothesis is provided based on an analysis of the Zeitgeist in the development of the psychologic theory associated with the disorder. We also concluded there is no evidence to support a linear relationship that establishes a psychologic predisposition to develop the disorder. Discussion: An analysis of the Zeitgeist when complex regional pain syndrome was first described helps to understand the long-standing theories associated with a psychological theory of its etiology. This understanding should help to undermine the perpetuation of such claims which may contribute to undertreatment and misdiagnosis. To be consistent with today s Zeitgeist we must incorporate psychologic aspects, which while not causal in nature or exclusive of complex regional pain syndrome, are strongly associated with a wide spectrum of chronic pain disorders.

Gilles de la Tourette’s syndrome (GTS) is a neuropsychiatric disorder that often presents with a complex array of motor and phonic tics that persist over the majority of a person’s life. GTS often presents with comorbidities such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and mood disorders. Psychosocial sequelae are also common among this population.We present the case of a 49-year-old female with severe, lifelong GTS complicated by OCD, inattention, impulsivity, disinhibition, mood disturbances, generalized anxiety, and pain secondary to motor tics. Habit reversal therapy (HRT) was used with full body relaxation conditioned as a competitive response to target her tics, anxiety, and pain simultaneously. The patient demonstrated significant reduction of symptoms and improvement in psychosocial status within four sessions. She was able to maintain this status at a 3 month follow-up session. Aspects of case conceptualization and therapeutic technique are discussed.

Sickle cell disease (SCD) affects developmental maturation causing a delay in secondary sex characteristics associated with puberty. There is little data on the impact of SCD on body image, a well-established risk factor for eating disorders among young women. Body dissatisfaction combined with environmental stressors and negative affect may place some men and women with SCD at a higher risk problematic eating behaviors or body change strategies in an attempt to achieve a more idealized body type. The present exploratory study examined the potential associations between SCD, body image, and eating disorders, and provided preliminary data to guide the directions of future investigations.

Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD.

Religion/spirituality has been identified by individuals with sickle cell disease (SCD) as an important factor in coping with stress and in determining quality of life. Research has demonstrated positive associations between religiosity/spirituality and better physical and mental health outcomes. However, few studies have examined the influence religiosity/spirituality has on the experience of pain in chronically ill patients. Our aim was to examine three domains of religiosity/spirituality (church attendance, prayer/Bible study, intrinsic religiosity) and evaluate their association with measures of pain. We studied a consecutive sample of 50 SCD outpatients and found that church attendance was significantly associated with measures of pain. Attending church once or more per week was associated with the lowest scores on pain measures. These findings were maintained after controlling for age, gender, and disease severity. Prayer/Bible study and intrinsic religiosity were not significantly related to pain in our study. Positive associations are consistent with recent literature, but our results expose new aspects of the relationship for African American patients. We conclude that religious involvement likely plays a significant role in modulating the pain experience of African American patients with SCD and may be an important factor for future study in other populations of chronically ill pain sufferers.

OBJECTIVE—Ragaglitazar is a novel insulin sensitizer with dual peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-α stimulating activities that improve plasma glucose and lipid profiles. The aim of the present dose-ranging study was to assess the efficacy and safety of ragaglitazar in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—This study included 177 hypertriglyceridemic type 2 diabetic subjects who participated in a 12-week, double-blind, parallel, randomized, placebo-controlled dose-ranging study (open pioglitazone arm). Subjects received ragaglitazar (0.1, 1, 4, or 10 mg), placebo, or pioglitazone (45 mg). Efficacy parameters included fasting plasma levels of triglycerides and glucose (FPG) along with other lipid levels, A1C, and insulin. RESULTS—Ragaglitazar in doses of 1, 4, and 10 mg resulted in a significant decrease from baseline as compared with placebo in FPG (−48, −74, −77 mg/dl) and triglycerides (−40, −62, −51%), free fatty acids (−36, −54, −62%), apolipoprotein B (−13, −29, −25%), LDL cholesterol (−14 and −19% for 4- and 10-mg groups), and total cholesterol (−16 and −15% for 4 and 10 mg) and a significant increase in HDL cholesterol (20 and 31% for 1- and 4-mg groups, respectively). Changes in triglycerides and FPG for pioglitazone treatment were similar to 1 mg ragaglitazar. Mean A1C values of the 1-, 4-, and 10-mg ragaglitazar and pioglitazone groups were significantly reduced compared with placebo (−0.5, −1.3, −1.1, and −0.3%, respectively). Common adverse events were edema, weight increase, leukopenia, and anemia. CONCLUSIONS—Ragaglitazar provided glycemic control that was comparable with that of pioglitazone and, compared with placebo, provided significant improvement in the lipid profile.

Purpose: To identify the characteristics of adult patients with newly diagnosed primary brain tumors associated with identifiable deficits in neuropsychologic function to target interventions to improve function and quality of life (QOL). Methods and materials: Adult patients with newly diagnosed primary brain tumors and their caregivers were enrolled and underwent a battery of standardized neuropsychologic tests, allowing for qualitative and quantitative assessment and sensitive to the effects of the brain tumor, QOL, or caregiver stress. Results: We enrolled 68 patients with no prior radiotherapy. Patients with left hemisphere tumors reported significantly more memory problems and depressive symptoms. They also exhibited poorer attention and were more distractible, with poorer verbal fluency and poorer verbal learning. Patients with glioblastoma multiforme demonstrated poorer psychomotor speed and visual tracking than patients with non–glioblastoma multiforme histologic features. Patients and caregivers perceived QOL in a similar fashion, with significant correlation between patient and caregiver on hope testing and general QOL on the Linear Analog Self-Assessment Scale. Conclusion: Patients with left hemisphere tumors and glioblastoma multiforme histologic features demonstrated testable differences in neuropsychologic function and QOL that may be amenable to improvement with medical therapy or tailored rehabilitation programs. Caregiver assessments can predict patient QOL, which may be useful in patients with declining status.

The impact of gender on the clinical characteristics, risk factors, co-morbidities, etiology, treatment and outcome of acute heart failure in sub-Saharan Africa has not been described before. The aim of this study was to evaluate the sex differences in acute heart failure in sub-Saharan Africa using the data from The sub-Saharan Africa Survey of Heart Failure (THESUS-HF).1,006 subjects were recruited into this prospective multicenter, international observational heart failure survey. The mean age of total population was 52.4 years (54.0 years for men and 50.7 years for women). The men were significantly older (p = 0.0045). Men also presented in poorer NYHA functional class (III and IV), p = 0.0364). Cigarette smoking and high blood pressure were significantly commoner in men (17.3 vs. 2.6% and 60.0 vs. 51.0% respectively). On the other hand, atrial fibrillation and valvular heart disease were significantly more frequent in women. The mean hemoglobin concentration was lower in women compared to men (11.7 vs. 12.6 g/dl, p ≤ 0.0001), while the blood urea and creatinine levels were higher in men (p0.0001). LV systolic dysfunctional was also seen more in men. Men also had higher E/A ratio indicating higher LV filling pressure. Outcomes were similar in both sexes.Although the outcome of patients admitted for AHF in sub-Saharan regions is similar in men and women, some gender differences are apparent suggesting that in men more emphasis should be put on modifiable life risk factors, while in women prevention of rheumatic heart diseases and improved nutrition should be addressed vigorously.

Differentiating somatic from emotional influences on the experience of chronic pain has been of interest to clinicians and researchers for many years. Although prior research has not well specified these pathways at the anatomical level, some evidence, both theoretical and empirical, suggest that emotional reactions influence the experience of disease and non-disease-related pains. Other studies suggest that treatments directed at negative emotional responses reduce suffering associated with pain. The current study was conducted to explore the influence of emotional reactions to pain as a predictor of psychological distress in a sample of adult Blacks with Sickle Cell Disease (SCD). Using cross-sectional survey data, we evaluated whether negative emotional reactions to the experience of pain were predictive of psychological distress after controlling for the somatic dimension of pain and age in n = 67 Black patients with Sickle Cell Disease (SCD). Results showed that greater negative emotion associated with pain predicted Somatization ( p < .01), Anxiety ( p < .05), Phobic Anxiety ( p < .05), and Psychoticism ( p < .05). Increased negative emotion associated with pain was also predictive of the General Symptoms Index ( p < .05) and the Positive Symptoms Total from the SCL-90-R ( p < .01). We believe the current study demonstrates that negative emotional reactions to the experience of pain in adults with SCD are predictive of psychological distress above and beyond the influences of age and the direct nociceptive experience. We also believe these data to be valuable in conceptualizing the allocation of treatment resources toward a proactive approach with early identification of patients who are responding poorly for the purpose of potentially reducing later psychopathology. A deeper understanding of the ways that subpopulations cope with chronic disease-related pain may produce models that can be ultimately generalized to the consumers of the majority of healthcare resources.

Background Elevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF. Methods We investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality. Results Mean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [ P = .030] and 1.97 [ P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [ P = .005] and 1.95 [ P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004). Conclusions Abnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.

The current paper provides a brief overview of research on the effects of race and ethnicity on pain. More specifically, the article reviews the utility of the concepts of race and ethnicity for pain research, suggests operational definitions of race and ethnicity, reviews the literature on the effects of race and ethnicity on laboratory and clinical pain, and provides suggestions for future research.

Background Although lifestyle interventions are often recommended in the management of chronic gout, the evidence from trial data of the benefits and safety of using lifestyle interventions for treating acute gout attacks have not previously been examined in a systematic review. Objectives The objective of this systematic review was to evaluate the benefits and safety of lifestyle interventions for the treatment of people with acute gout. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for studies (up to 5 April 2013). We also searched the 2010 to 2011 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of included articles. Selection criteria Studies were included if they were randomised or quasi-randomised controlled trials which compared lifestyle interventions to another therapy (active or placebo) in patients with acute gout. Outcomes of interest were the change in participant-reported pain in the target joint(s), target joint inflammation and function, health-related quality of life (HRQoL), patient global assessment, study participant withdrawals due to adverse events (AEs) and serious adverse events (SAEs). Data collection and analysis Two review authors independently applied methods recommended by The Cochrane Collaboration for the selection, appraisal, data collection and synthesis of studies. We assessed the quality of the body of evidence for each outcome using the GRADE approach. Main results Only one study (19 participants) at high risk of bias was included in the review. Patients were randomised to receive oral prednisolone and colchicine with or without concomitant topical ice therapy. Topical ice therapy provided significant additional benefit over oral prednisolone and colchicine alone with respect to pain, but did not significantly reduce swelling during acute gout episodes. Mean pain reduction with standard medical treatment was 4.4 cm on a 0 to 10 cm visual analogue scale (VAS) after one week; the addition of topical ice reduced pain by an additional 3.33 cm (95% CI 5.84 to 0.82), or an absolute reduction of 33% (8% to 58% reduction). Joint swelling was reduced by a mean of 3.8 cm in the standard medical treatment group; the addition of topical ice therapy did not reduce swelling significantly (mean difference (MD) 2.07 cm, 95% CI -1.56 to 5.70). Target joint function, HRQoL, patient global assessment, study participant withdrawals due to AEs and SEAs were not reported in this study. Authors' conclusions There is low quality evidence, from a single trial at high risk of bias, that the addition of topical ice therapy to oral prednisolone and colchicine for oligoarticular attacks of acute gout results in significantly greater pain reduction at one week.

Peripheral pain and ataxic tremor can appear suddenly following thalamic stroke and can significantly alter a patient's psychological, social, and physical functioning. The present paper reports the case of a 70-year-old Caucasian female who sustained an acute left posterior cerebral artery infarction involving the thalamus and left mesiotemporal regions. She subsequently developed Central Poststroke Pain and ataxic movement of her right arm and hand in addition to a significant right-side claudication. She was treated over 16 weeks (6 weeks of EMG biofeedback and 10 weeks of psychotherapy) with a combination of EMG biofeedback, progressive muscle relaxation, behavioral pain coping skills training, Forced Use Therapy, and Cognitive Behavioral Therapy 7 years after her initial cerebral accident. The case demonstrates the utility of biofeedback when combined as part of a comprehensive treatment program to address the multiple complications associated with thalamic stroke.

The authors report on results from a new procedure for evaluating adequacy of effort given during neuropsychological testing. The letter memory test (LMT) is a computer-administered, 45-item, forced-choice recognition task that uses consonant letters as stimuli and manipulates face difficulty level along 2 dimensions: number of letters to be remembered and number of choices amongst which the target stimulus must be identified. In 3 studies that included either analogue or known groups designs, the LMT discriminated poorly motivated from well-motivated groups at a moderately high level of accuracy, which was comparable to that of the Digit Memory Test and superior to that of the 21-Item Test. The internal consistency reliability of the LMT was also high.

Background Although lifestyle interventions are commonly recommended in the management of patients with chronic gout, the evidence from trial data for their benefits and safety has not been previously examined in a systematic review. Objectives The objective of this systematic review was to evaluate the benefits and safety of lifestyle interventions for the treatment of people with chronic gout. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for studies on 5 April 2013. We also searched the 2010 to 2011 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of included articles. Selection criteria Studies were included if they were randomised or quasi-randomised controlled trials (RCTs or CCTs) which compared lifestyle interventions to another therapy (active or placebo) in patients with chronic gout. Outcomes of interest were changes in gout attack frequency, joint pain, serum urate levels, tophus size, function, quality of life and adverse effects. Data collection and analysis Two review authors independently applied methods recommended by The Cochrane Collaboration for the selection, appraisal, data collection and synthesis of studies. We assessed the quality of the body of evidence for each outcome using the GRADE approach. Main results Only one study (120 participants), at moderate risk of bias, was included in the review. Patients were randomised to one of three interventions: either skim milk powder (SMP) enriched with glycomacropeptide (GMP) and G600, non-enriched SMP or lactose powder, over a three-month period. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. Low quality evidence indicated that there was no difference between the SMP/GMP/G600 group and combined control groups (SMP and lactose powder) at three months (mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34). There were no significant between-group differences in terms of withdrawals due to adverse effects (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03), and serious adverse events resulting in hospitalisation (2/40 SMP/GMP/G600 group versus 3/80 controls; RR 1.33, 95% CI 0.23 to 7.66). Gastrointestinal adverse effects were the most commonly reported. Pain from self reported gout flares, measured on a 10-point Likert scale, improved more in the SMP/GMP/G600 group compared to controls (MD -1.03, 95% CI -1.96 to -0.10), an absolute difference of 10% (absolute risk difference -0.10, 95% CI -0.20 to -0.01). This is unlikely to be of clinical significance. There was no significant difference in physical function between SMP/GMP/G600 and the control groups at three-month followup (MD -0.03, 95% CI -0.14 to 0.08). Tophus regression and serum urate normalisation were not reported in this study. Authors' conclusions While there is good evidence from observational studies of an association between various lifestyle risk factors and gout development, there is a paucity of high-quality evidence from randomised controlled trials to either support or refute the use of lifestyle modifications for improving outcomes in people with chronic gout.

Objective To elucidate factors that influence African American willingness to participate in health-related research studies. Methods The African American Alzheimer disease research study group at North Carolina A&T State University designed an in-person questionnaire and surveyed more than 700 African American adults on their willingness to participate in health-related research studies. The questionnaire was distributed and collected in a nonclinical setting during the years 2008 and 2009. This study was approved by the North Carolina A&T State University Institutional Review Board. Results Of the 733 valid respondents, 16% had previously participated in a health-related research study. Of these, more than 90% were willing to participate again in future research studies. Of the 614 who had never participated in a research study, more than 70% expressed willingness to participate. The majority (75%) of experienced research study participants (RSP) were older than 40 years compared with 45% of non-research study participants. Experienced research participants were also twice as likely to have a college degree compared with non-research study participants. Seventy-three percent of non-research study participants were willing to participate in research studies in the future. The factors that were probable impediments to participation included lack of time and trust. Men with knowledge of the Tuskegee Syphilis Study were 50% less likely to be willing to participate compared with those who had not heard of Tuskegee Syphilis Study. Conclusions African Americans are willing to participate in health-related research studies. Several factors such as the appropriate incentives, community trust building, outreach, and community partnership creation are necessary for engaging minority participants. Incorporating factors that target African American enrollment in research design and implementation, such as increased training of minority health ambassadors and African American researchers and public health specialists, are needed to better engage minorities across generations, in research.

We thank the authors for their interest in our study. Its main message is that short-term increases in serum creatinine, such as those that can be detected in patients undergoing aggressive diuretic treatment for acutely decompensated heart failure, do not necessarily predict a poor prognosis because they may be secondary to hemodynamic mechanisms (renal hypoperfusion and arterial underfilling) related to aggressive diuretic treatment in the absence of a persistent kidney injury.1 Data in the literature are controversial with respect to the prognostic significance of short-term serum creatinine changes. When serum creatinine levels were not assessed prospectively in every patient,2,3 …

Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered “silent carriers”. Published evidence however supports a complex behavioral phenotype or trait – intense creative energy (“ICE”)-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14–22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase ( MTHFR ) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from JRA to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets can be defined using A1AT , MTHFR and APOE genotyping. Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes. These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to selective advantages: ICE phenotype and disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes.

Background: Previous studies have suggested that a lower lymphocyte ratio (Ly%) in the white blood cell (WBC) differential count is related to worse outcomes in patients with acute heart failure (AHF) and other cardiovascular disorders. Methods: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood pressure >125 mm Hg and brain natriuretic peptide ≧350 pg/ml or equivalent were randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for 6 months following randomization. Complete blood count and differential were performed by a central laboratory at baseline and then daily to day 5 and on day 14. Results: The WBC count by itself was not associated with measures of disease severity or outcome, and patients with Ly% 13%, except for a higher baseline WBC count, elevated baseline glucose, older age and higher rates of peripheral vascular disease. However, patients with Ly% Conclusions: Despite no association with any baseline characteristic known to strongly predict outcome in AHF, low Ly% is associated with less symptom relief and worse in-hospital and postdischarge clinical outcomes.