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Abstract Background The life expectancy for individuals with sickle cell disease (SCD) has greatly increased over the last 50 years. Adults with SCD experience multiple complications such as cardiopulmonary disease, strokes, and avascular necrosis that lead to limitations that geriatric populations often experience. There are no dedicated instruments to measure functional decline and functional age to determine risk of future adverse outcomes in older adults with SCD. The objective of this study was to assess the feasibility of performing the Sickle Cell Disease Functional Assessment (SCD-FA). Methods We enrolled 40 adults with SCD (20 younger adults aged 18–49 years as a comparison group and 20 older adults aged 50 years and older) in a single-center prospective cohort study. Participants were recruited from a comprehensive sickle cell clinic in an academic center in the southeastern United States. We included measures validated in an oncology geriatric assessment enriched with additional physical performance measures: usual gait speed, seated grip strength, Timed Up and Go, six-minute walk test, and 30-second chair stand. We also included an additional cognitive measure, which was the Montreal Cognitive Assessment, and additional patient-reported measures at the intersection of sickle cell disease and geriatrics. The primary outcome was the proportion completing the assessment. Secondary outcomes were the proportion consenting, duration of the assessment, acceptability, and adverse events. Results Eighty percent (44/55) of individuals approached consented, 91% (40/44) completed the SCD-FA in its entirety, and the median duration was 89 min (IQR 80–98). There were no identified adverse events. On the acceptability survey, 95% (38/40) reported the length as appropriate, 2.5% (1/40) reported a question as upsetting, and 5% (2/40) reported portions as difficult. Exploratory analyses of physical function showed 63% (25/40) had a slow usual gait speed (

Abstract Background The life expectancy for people with sickle cell disease (SCD) has improved tremendously over the last 50 years. This population experiences hemolysis and vaso-occlusion in multiple organs that lead to complications such as cardiopulmonary disease, strokes, and avascular necrosis. These complications can limit mobility and aerobic endurance, similar to limitations that often occur in geriatric populations. These sickle-cell and age-related events lead to frequent hospitalization, which further increases the risk of functional decline. We have few tools to measure functional decline in people with SCD. The purpose of this paper is to describe a protocol to evaluate the feasibility of sickle cell disease geriatric assessment (SCD-GA). Methods/design We will enroll 40 adults with SCD (20 age 18–49.99 years and 20 age ≥ 50 years) in a prospective cohort study to assess the feasibility of SCD-GA. The SCD-GA includes validated measures from the oncology geriatric assessment enriched with additional physical and cognitive measures. The SCD-GA will be performed at the first study visit, at 10 to 20 days after hospitalization, and at 12 months (exit visit). With input from a multidisciplinary team of sickle cell specialists, geriatricians, and experts in physical function and physical activity, we selected assessments across 7 domains: functional status (11 measures), comorbid medical conditions (1 measure), psychological state (1 measure), social support (2 measures), weight status (2 measures), cognition (3 measures), and medications (1 measure). We will measure the proportion completing the assessment with feasibility as the primary outcome. Secondary outcomes include the proportion consenting and completing all study visits, duration of the assessment, acceptability, and adverse events. Discussion We present the protocol and rationale for selection of the measures included in SCD-GA. We also outline the methods to determine feasibility and subsequently to optimize the SCD-GA in preparation for a larger multicenter validation study of the SCD-GA.

We studied rickettsioses in southern Sri Lanka. Of 883 febrile patients with paired serum samples, 156 (17.7%) had acute rickettsioses; rickettsioses were unsuspected at presentation. Additionally, 342 (38.7%) had exposure to spotted fever and/or typhus group rickettsioses and 121 (13.7%) scrub typhus. Increased awareness of rickettsioses and better tests are needed.

Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults.

To determine the proportion of fevers caused by leptospirosis, we obtained serum specimens and epidemiologic and clinical data from patients in Galle, Sri Lanka, March–October 2007. Immunoglobulin M ELISA was performed on paired serum specimens to diagnose acute (seroconversion or 4-fold titer rise) or past (titer without rise) leptospirosis and seroprevalence (acute). We compared (individually) the diagnostic yield of acute-phase specimens and clinical impression with paired specimens for acute leptospirosis. Of 889 patients with paired specimens, 120 had acute leptosoirosis and 241 had past leptospirosis. The sensitivity and specificity of acute-phase serum specimens were 17.5% (95% confidence interval [CI] 11.2%–25.5%) and 69.2% (95% CI 65.5%–72.7%), respectively, and of clinical impression 22.9% (95% CI 15.4%–32.0%) and 91.7% (95% CI 89.2%–93.8%), respectively. For identifying acute leptospirosis, clinical impression is insensitive, and immunoglobulin M results are more insensitive and costly. Rapid, pathogen-based tests for early diagnosis are needed.

Although individuals with sickle cell disease (SCD) are at increased risk for stroke, the underlying pathophysiology is incompletely understood. Intracardiac shunting via a patent foramen ovale (PFO) is associated with cryptogenic stroke in individuals without SCD. Recent evidence suggests that PFOs are associated with stroke in children with SCD, although the role of PFOs in adults with stroke and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs. The first patient had hemoglobin SC and presented with a transient ischemic attack and a subsequent ischemic stroke. There was no evidence of cerebral vascular disease on imaging studies and the PFO was closed. The second patient had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT). Chronic transfusion therapy was recommended, and the DVT was managed with warfarin. The PFO was not closed, and the patients' neurologic symptoms were stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the literature review illustrate the dire need for further research to evaluate PFO as a potential risk factor for stroke in adults with SCD.

BACKGROUND:Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue. METHODOLOGY/PRINCIPAL FINDINGS:The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians' subjective clinical diagnosis (gestalt clinical impression) in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children), including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians' clinical diagnosis for identification of acute dengue (71.5% vs 67.1%), but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%). The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3%) patients had evidence of plasma leakage and 16 (4.1%) had evidence of bleeding. CONCLUSIONS/SIGNIFICANCE:In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue in adults versus children. The 2009 WHO dengue classification criteria had high sensitivity but low specificity compared to physicians' gestaldt diagnosis. Large cohort studies will be needed to validate the diagnostic yield of clinical impression and specific features for dengue relative to the 2009 WHO classification criteria.

BACKGROUND:Dengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005-2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1. In 2007, we conducted etiologic surveillance of acute febrile illness in the Southern Province and confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1 identified. To re-evaluate the importance of dengue as an etiology of acute febrile illness in this region, we renewed fever surveillance in the Southern Province to newly identify and characterize dengue. METHODOLOGY/PRINCIPAL FINDINGS:A cross-sectional surveillance study was conducted at the largest tertiary care hospital in the Southern Province from 2012-2013. A total of 976 patients hospitalized with acute undifferentiated fever were enrolled, with 64.3% male and 31.4% children. Convalescent blood samples were collected from 877 (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976 hospitalizations, with most cases (291, 75.0%) confirmed virologically and by multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%) were due to DENV-1. Acute dengue was associated with self-reported rural residence, travel, and months having greatest rainfall. Sequencing of selected dengue viruses revealed that sequences were most closely related to those described from China and Southeast Asia, not nearby India. CONCLUSIONS/SIGNIFICANCE:We describe the first epidemic of DENV-1 in the Southern Province of Sri Lanka in a population known to be susceptible to this serotype because of prior study. Dengue accounted for 40% of acute febrile illnesses in the current study. The emergence of DENV-1 as the foremost serotype in this densely populated but agrarian population highlights the changing epidemiology of dengue and the need for continued surveillance and prevention.

Chikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after a 40-year hiatus. We sought to identify and characterize acute chikungunya infection (CHIK) in patients presenting with acute undifferentiated febrile illness in unstudied rural and semi-urban southern Sri Lanka in 2007.We enrolled febrile patients ≥ 2 years of age, collected uniform epidemiologic and clinical data, and obtained serum samples for serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR). Serology on paired acute and convalescent samples identified acute chikungunya infection in 3.5% (28/797) patients without acute dengue virus (DENV) infection, 64.3% (18/28) of which were confirmed by viral isolation and/or real-time RT-PCR. No CHIKV/DENV co-infections were detected among 54 patients with confirmed acute DENV. Sequencing of the E1 coding region of six temporally distinct CHIKV isolates (April through October 2007) showed that all isolates posessed the E1-226A residue and were most closely related to Sri Lankan and Indian isolates from the same time period. Except for more frequent and persistent musculoskeletal symptoms, acute chikungunya infections mimicked DENV and other acute febrile illnesses. Only 12/797 (1.5%) patients had serological evidence of past chikungunya infection.Our findings suggest CHIKV is a prominent cause of non-specific acute febrile illness in southern Sri Lanka.

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Context: Perceived discriminatory experiences in society have been associated with a higher burden of pain among some minority patient populations., Objectives: To describe the extent to which patients with sickle cell disease (SCD) perceive discrimination from health care providers and to examine the association of these experiences with the burden of chronic SCD pain., Methods: Cross-sectional analysis of data collected at baseline of a prospective cohort study of SCD patient experiences of care (n = 291). Perceived race-based and disease-based discrimination from health care providers were measured using subscales adapted from the Interpersonal Processes of Care Survey. Discrimination scores were examined for their association with patient characteristics and measures of pain burden using descriptive, bivariate, and multivariate analytic techniques., Results: Respondents reported a greater burden of race-based discrimination from health care providers than has been previously reported by African Americans, and they reported a greater amount of disease-based vs. race-based discrimination. Age and having difficulty persuading providers about pain were the only patient characteristics independently associated with race-based discrimination, whereas older age, greater emergency room utilization, having difficulty persuading providers about pain, daily chronic pain, fewer good days during a week, and a higher severity of pain on their good days were independently associated with greater disease-based discrimination., Conclusion: Perceived disease-based, but not race-based, discrimination was found to be associated with a greater range of self-reported pain among patients with SCD. If causal, this finding could signal an important new approach to mitigating the burden of pain experienced by persons with SCD., (Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess disparities in the quality of healthcare provider communication experienced by African-American adults with and without sickle cell disease (SCD) in the U.S., Methods: Poor provider communication was assessed by the Provider Communication subscale of the Consumer Assessment of Healthcare Plans and Systems survey. The SCD sample was obtained from participants in a multicenter observational study of healthcare experiences. The national African-American sample data was obtained from published national estimates., Results: The SCD sample was more likely than the national sample to report poor communication in 3 out of 4 communication domains: listening (22.3% vs. 11.5%, p<0.0001); showing respect (26.1% vs. 9.5%, p<0.0001); and spending enough time (38.3% vs. 16.2%, p<0.0001). Differences were consistent in young, but not old, patients and showed some variation by self-reported health status and education., Conclusions: The communication difficulties experienced by persons with SCD do not appear reducible to their predominantly African-American race, but may result from more disease-specific factors., Practice Implications: Healthcare providers should take particular care in recognizing and demonstrating recommended communication skills with SCD patients as these patients may be particularly vulnerable to, and cognizant of, poor quality interactions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)