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Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort. Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation. Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality. Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies. ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/

Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

Background Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease. Methods Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index and Beck Depression Inventory II screening measures as a cross-sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16 (Beck Depression Inventory II) defined sleep disturbance and depression, respectively. Clinical and laboratory parameters were also assessed. Results The mean Pittsburgh Sleep Quality Index score was 8.4 (SD ± 4.2) indicating a 71.2% prevalence of sleep disturbance. The mean Beck Depression Inventory II score was 8.0 (SD ± 8.9). Sixty five (20.6%) participants had a score indicating depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh Sleep Quality Index and Beck Depression Inventory II scores were significantly correlated (p < .001). The number of days with mild/moderate pain (p = .001) and a history of headaches (p = .005) were independently associated with depression by multivariate regression analysis. Patients with sleep disturbance were older (p = .002), had higher body mass index (p = .011), had more days of pain (p = .003) and more frequent severe acute painful events (emergency room visits and hospitalizations) during the previous 12 months (p < .001). Conclusions More than 70 percent of adults with sickle cell disease had sleep disturbance, while 21 percent showed evidence of clinical depression. Sleep disturbance and depression were correlated, and were most common among those with more frequent pain. Providers caring for adults with sickle cell disease and frequent pain should consider screening for these common co-morbidities. Additional study is needed to confirm these findings and to determine if treatments for pain, depression or sleep disturbances will improve quality of life measures in this patient population. Trial registration ClinicalTrials.gov identifier: NCT00011648 .

Background Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort. Methods Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation. Results Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality. Conclusions Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies. Trial Registration ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/

This study evaluated, analyzed, and assessed the reasons for the low level of advancement of African American women into CEO-level positions within the banking industry in Chicago, Illinois. Related to these observations, there were several purposes for the execution of this dissertation. The core purpose of this research was to identify workplace barriers (for example, glass ceilings and stereotypes) to African American women attempting to achieve the highest employment positions in banking. This study took a closer look at some of the factors African American woman faced when attempting to receive senior-level promotions. Further, this study sought to determine which specific behaviors, characteristics, and/or educational backgrounds can lend to the maintenance of CEO-level jobs for African American women in the banking industry. An extensive literature review was conducted to examine the perceptions and success of various leadership styles (e.g., transformational leadership) used by African American women in achieving these goals. The study sought to begin considerable academic debate on the topic that will eventually effect positive change for African American women within the banking industry. The findings suggest that many of those interviewed and surveyed saw a correlation between the culture of the banking industry and the low promotion rate of African American women to CEO-level positions. These findings are supported by the barriers identified in the survey results and interviews. The interviewees concluded that, for more African American women to obtain CEO-level promotions, they need a substantially higher level of mentors. This study further revealed that being a self-starter, showing aggression and assertiveness, networking, and having self-confidence were key components in not only securing but also maintaining a CEO-level position within banking. Although findings also supported the perception of a glass ceiling for African American women, results show a hope for African American women within the banking industry to matriculate to CEO-level positions.

A generalist approach to practice with families affected by parental addiction is presented. Using a model program for working with parents and children who have been affected by substance abuse, the article illustrates the application of the problem-solving process to effect change at multiple levels, including individual, family, community, organizational, and policy-making levels. The authors describe assessment and intervention strategies at each of these levels and conclude with an evaluation of the project's success.

Freshwater microbialites (i.e., lithifying microbial mats) are quite rare in northern latitudes of the North American continent, with two lakes (Pavilion and Kelly Lakes) of southeastern BC containing a morphological variety of such structures. We investigated Kelly Lake microbialites using carbon isotope systematics, phospholipid fatty acids (PLFAs) and quantitative PCR to obtain biosignatures associated with microbial metabolism. δ13CDIC values (mean δ13CDIC −4.9 ± 1.1‰, n = 8) were not in isotopic equilibrium with the atmosphere; however, they do indicate 13C-depleted inorganic carbon into Kelly Lake. The values of carbonates on microbialite surfaces (δ13C) fell within the range predicted for equilibrium precipitation from ambient lake water δ13CDIC (−2.2 to −5.3‰). Deep microbialites (26 m) had an enriched δ13Ccarb value of −0.3 ± 0.5‰, which is a signature of photoautotrophy. The deeper microbialites (>20 m) had higher biomass estimates (via PLFAs), and a greater relative abundance of cyanobacteria (measured by 16S copies via qPCR). The majority of PLFAs constituted monounsaturated and saturated PLFAs, which is consistent with gram-negative bacteria, including cyanobacteria. The central PLFA δ13C values were highly depleted (−9.3 to −15.7‰) relative to δ13C values of bulk organic matter, suggesting a predominance of photoautotrophy. A heterotrophic signature was also detected via the depleted iso- and anteiso-15:0 lipids (−3.2 to −5.2‰). Based on our carbonate isotopic biosignatures, PLFA, and qPCR measurements, photoautotrophy is enriched in the microbialites of Kelly Lake. This photoautotrophy enrichment is consistent with the microbialites of neighboring Pavilion Lake. This indication of photoautotrophy within Kelly Lake at its deepest depths raises new insights into the limits of measurable carbonate isotopic biosignatures under light and nutrient limitations.

IntroductionChronic pain, defined as persistent or recurring pain or pain lasting longer than 3 months, is a common childhood problem and can profoundly impact children’s physical, psychological and social functioning. The last comprehensive systematic review estimating the prevalence of chronic pain in children and adolescents was published in 2011. Since then, the literature on paediatric chronic pain has grown substantially. This manuscript outlines a protocol for an updated systematic review to provide updated estimates of the prevalence of various forms of chronic pain in children and adolescence. The review will also examine the relationship between sociodemographic and psychosocial factors related to chronic pain prevalence.Methods and analysisThis review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search EMBASE, PubMed, CINAHL and PsycINFO for observational studies published in English between 2009 and 2020 reporting population-based estimates of chronic non-disease-related pain prevalence in children or adolescents (age ≤19 years). Two independent reviewers will screen the titles and abstracts retrieved from the search based on predefined eligibility criteria. The full texts of relevant studies will then be assessed by two reviewers. Studies meeting inclusion criteria will be categorised according to the type of pain investigated: headache only, abdominal pain only, back pain only, musculoskeletal pain, combined pain, general pain and other pain. Data will be extracted using customised forms and studies will be assessed for risk of bias using a 10-item tool developed by Hoy et al (2012). A narrative synthesis will summarise the prevalence estimates of paediatric chronic pain and associated sociodemographic and psychosocial correlates. Meta-analyses and meta-regressions will be performed if the data permit.Ethics and disseminationEthical approval is not required. Findings will be disseminated through publication in an academic journal, presentations at conferences and in various media.PROSPERO registration numberCRD42020198690.