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Diabetes Mellitus , Pé Diabético , Barbados/epidemiologia , Custos e Análise de Custo , Humanos , CicatrizaçãoRESUMO
BACKGROUND: Sickle cell disease is a group of genetic diseases which is especially prevalent in tropical and subtropical regions; however, forced migration and ongoing population movement have spread it throughout the world, with estimated birth rates reaching 0.49 per 1000 in the Americas, 0.07 per 1000 in Europe, 0.68 per 1000 in South and Southeast Asia, and 10.68 per 1000 in Africa. Life for individuals with sickle cell disease can be affected by repeated acute complications and compounded by progressive organ damage. Studies reveal that when people with chronic illness learn self-management, their clinical outcomes and quality of life improves; and they show lower dependence on healthcare services. There are, however, no reviews identifying which interventions improve knowledge and little is known about the impact of patient or care-giver knowledge on clinical and psychosocial outcomes in people with sickle cell disease. OBJECTIVES: 1. To determine the effectiveness of patient- and caregiver-centred educational interventions for changing knowledge and understanding of sickle cell disease among patients as well as caregivers of people with the disease.2. To assess the effectiveness and safety of patient- and caregiver-centred educational interventions and programs for the recognition of signs and symptoms of disease-related morbidity, adherence to treatment and healthcare utilization in patients with sickle cell disease. SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of last search: 11 April 2016. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials which evaluate the effectiveness of individual- and group-based interventions for either the patient with sickle cell disease or their caregivers, or both. Eligible interventions will aim to change knowledge, attitudes or skills, improve psychosocial aspects of the disease as well as treatment adherence and healthcare utilization. Trials evaluating the intervention versus no program, comparing two interventions and those which are part of a multi-faceted intervention to improve a range of sickle cell-related health outcomes are all eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials based on stated inclusion criteria and thereafter examined each selected report to extract data using a prepared, piloted, data collection form. A third author assisted in reaching consensus if there were any discrepancies. Similarly, risk of bias was assessed by two authors and verified by a third author. MAIN RESULTS: A total of 12 trials (11 randomized controlled trials and one quasi-randomized trial) of 563 people with HbSS, HbSC or HbSßthal, aged six to 35 years old, were included in the review; the majority of participants were African-American. Interventions ranged from a total of one hour to weekly sessions for eight weeks and the post-intervention assessments ranged from the end of the intervention period to 12 months after completion. The heterogeneity of the included trials, which encompasses setting, inclusion and exclusion criteria, interventional method and time of assessment, ranged from 'not important' to 'moderate to substantial' for different review outcomes. The overall risk of bias was low for selective reporting, unclear for random sequence generation, allocation concealment, blinding of participants and blinding of outcome assessment. Incomplete outcome reporting and blinding of personnel showed mixed bias representations.Patient knowledge was assessed by four trials (160 participants) with moderate to substantial heterogeneity. There was evidence that educational programs improved patient knowledge, standardised mean difference 0.87 points (95% confidence interval 0.28 to 1.45, moderate quality evidence), which improved further when a trial with high bias was removed in a sensitivity analysis. Caregiver knowledge, reported in a single trial of 20 families, also showed an improvement, standardised mean difference 0.52 points (95% confidence interval 0.03 to 1.00, moderate quality evidence). The effect on patient knowledge was sustained at longer follow-up periods, whereas the effect on caregiver knowledge was not sustained.There were two primary outcomes related to the effectiveness of educational programs on the recognition of signs and symptoms of disease-related morbidity. No comparative data were reported for patients or caregivers (or both) recognising signs and symptoms leading to self-management. Data from two trials were analysed for the utilization of health services and showed no evidence of an effect, mean difference 0.33 (95% confidence interval -0.57 to 1.23, moderate quality evidence).With regard to the review's secondary outcomes, depression showed a statistically significant decline in intervention groups, standardised mean difference -0.66 points (95% confidence interval -1.18, to -0.14, moderate quality evidence). Adherence to treatment was not assessed in any of the identified trials. No effects of interventions were seen on coping, family relationships or health-related quality of life of patients.The quality of evidence was low for positive coping and moderate for child knowledge, healthcare utilization and depression. This suggests that further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimates. AUTHORS' CONCLUSIONS: This review identifies important positive effects of educational interventions on improving patient knowledge of sickle cell disease and depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effect on knowledge was significant but small and whether it offers any clinical benefit is uncertain. Significant factors limiting these effects could be trials being under powered as well as attrition rates. Effects were not statistically significant in assessments of secondary outcomes, possibly due to the paucity of the number of trials and patients and caregivers. Trials showed moderate to high heterogeneity which might impact the results. To better study effects on outcomes, further controlled trials are needed with rigorous attention given to improve recruitment and retention and to decrease bias. Predetermined protocols using similar measurements should be used across multiple sites.
Assuntos
Anemia Falciforme/complicações , Cuidadores/educação , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Adolescente , Adulto , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The aim of this study was to establish the prevalence and risk factors for intergenerational (IG)-sex in females aged 15-19 residing in Barbados. METHODS: This cross sectional cluster survey was conducted in a 2.6% national sample in the age range (n = 261) recruited from multiple polling districts chosen with a probability proportional to size. Consent was obtained from participants aged ≥18 years or from parents/guardians of participants <18 years, with participant assent. The prevalence of age at first sex was analyzed using a life table approach and risk factors for IG sex (defined as sexual relations with a male 10 or more years older) were analyzed by logistic regression, adjusting for age. RESULTS: 51.0% of adolescent females in the survey reported ever having had sex, among whom prevalence of IG-sex was 13.2% (95% CI: 6.7-19.8) at first sex, 29.0% (22.3-35.7) within the preceding twelve months, and 34.8% (24.3-45.4) ever. Condom use at first sex was positively related to willingness to have sex (F statistic = 9.8, p = 0.001). The strongest determinant for IG-sex was age of sexual debut (age adjusted Odds Ratio [95% CI]: 0.58[0.41-0.83]), followed by money or gifts received from the partner (2.91[1.17-7.23] and self-esteem (0.33[0.11-0.95]). CONCLUSIONS: The survey establishes a high rate of IG-sex in Barbados, a 'high income' country. Most insightful is that risk of IG-sex nearly halved for every year at which first sex was delayed. A high proportion of coerced sex was reported at first sexual experience and this was linked to poor condom use. Affirmative prevention approaches are recommended to boost self-acclamation of adolescent women within less coercive relationships, especially during their first sexual encounter.
Assuntos
Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Sexo sem Proteção/estatística & dados numéricos , Adolescente , Fatores Etários , Barbados , Coerção , Preservativos/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Prevalência , Fatores de Risco , Autoimagem , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The Barbados Diabetes Remission Study-2 reported that a low-calorie diet for weight loss and diabetes remission implemented within the community and supported by trained community health advocates was both an acceptable implementation strategy and a clinically effective intervention. This study aimed to examine the adaptability of the face-to-face protocol into an online modality. METHODS: The Iterative Decision-making for Evaluation of Adaptations (IDEA) framework guides researchers in examining the necessity of the adaptation and the preservation of core intervention elements during the adaptation process. Adaptation outcomes were documented using the Framework for Reporting Adaptations and Modifications to Evidence-Based Implementation Strategies (FRAME-IS). Implementation outcome was determined by fidelity to core elements. Intervention effectiveness was determined from the analysis of clinical data. RESULTS: We decided that an adaptation was needed as COVID-19 control measures prohibited in-person interactions. The core elements-i.e. 12-week intervention duration, daily 840-kcal allowance, and weekly monitoring of weight and blood glucose-could be preserved during the adaptation process. Adaptations were made to the following: (1) the context in which data were collected-participants self-measured at home instead of following the original implementation strategy which involved being measured by community health advocates (CHA) at a community site; (2) the context in which data were entered-participants posted their measurements to a mobile application site which was accessible by CHAs. As with the original protocol, CHAs then entered the measurements into an online database; (3) the formulation of the low-calorie diet-participants substituted the liquid formulation for a solid meal plan of equivalent caloric content. There was non-inferiority in fidelity to attendance with the online format (97.5% visit rate), as compared to the face-to-face modality (95% visit rate). One participant deviated from the calorie allowances citing difficulty in estimating non-exact portion sizes and financial difficulty in procuring meals. Weight change ranged from - 14.3 to 0.4 kg over the 12-week period, and all group members achieved induction of diabetes remission as determined by a FBG of < 7mmol/l and an A1C of < 6.5%. CONCLUSION: The results suggest that this adapted online protocol-which includes changes to both the implementation strategy and the evidence-based practice-is clinically effective whilst maintaining fidelity to key elements. Utilization of the IDEA and FRAME-IS adaptation frameworks add scientific rigour to the research. TRIAL REGISTRATION: ClinicalTrials.gov NCT03536377 . Registered on 24 May 2018.
RESUMO
OBJECTIVES: The aims of this feasibility study were to (1) examine the implementation of a community-based health advocate (CHA) training programme to develop the clinical skills needed to support a diabetes remission protocol based on a low-calorie diet (LCD) and (2) investigate if participant weight loss can be achieved and diabetes remission induced under these conditions. METHODS: This tripartite study followed a type 2 implementation-effectiveness design. Three faith-based organisations (FBOs) were purposively selected as study sites. Implementation outcomes were guided by the Consolidated Framework for Implementation Research. During the pre-implementation phase, site 'readiness' to facilitate the intervention was determined from a site visit and an interview with the FBOs' leadership. During the implementation phase, congregants could volunteer for the 10-week CHA training which included practical exercises in weight, glucose and blood pressure (BP) measurement, and a summative practical assessment. Acceptability and implementation effectiveness were assessed via survey. During the intervention phase, other congregants and community members with T2DM or pre-diabetes and overweight were invited to participate in the 12-week LCD. Anti-diabetic medication was discontinued on day 1 of the intervention. Clinical effectiveness was determined from the change in weight, fasting blood glucose (FBG) and BP which were monitored weekly at the FBO by the CHA. HbA1C was performed at weeks 1 and 12. RESULTS: The FBOs were found to be ready as determined by their adequate resources and engagement in health-related matters. Twenty-nine CHAs completed the training; all attained a passing grade at ≥1 clinical station, indicating implementation effectiveness. CHA feedback indicated that the programme structure was acceptable and provided sufficient access to intervention-related material. Thirty-one persons participated in the LCD (11 T2DM:20 pre-diabetes). Mean (95%CI) weight loss was 6.0 kg (3.7 to 8.2), 7.9 kg in males vs 5.7 kg in females; A1C (%) decreased from 6.6 to 6.1, with a greater reduction in those with T2DM when compared to pre-diabetes. FBG decreased from 6.4 to 6.0mmol/L. T2DM remission rates were 60% and 90% by A1C<6.5% and FBG<7mmol/L respectively. Pre-diabetes remission was 18% and 40% by A1C<5.7% and FBG<5.6 respectively. CONCLUSION: Implementation of a community-based diabetes remission protocol is both feasible and clinically effective. Its sustainability is to be determined. Adaptability to other disorders or other settings should be investigated. TRIAL REGISTRATION: NCT03536377 registered on 24 May 2018.
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The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the latter phase is controlled by alternatively activated macrophages (M2) to resolve inflammation and promote tissue remodelling with the release of growth factors. In a simple human inflammatory response, such as acute crystal arthropathy, macrophages progress linearly through M1 and M2 phases; however, in chronic inflammatory responses, such as atherosclerosis and Diabetic Nephropathy (DN), both M1 and M2 macrophages may coexist, leading to persistent inflammation and fibrosis. A key macrophage receptor that regulates conversion from M1 to M2 is CD163, the hemoglobin scavenger receptor. Scavenging of hemoglobin:haptoglobin (Hb:Hp) complexes via CD163 leads to nuclear translocation of the transcription factor Nrf2 (NF-E2-related factor 2), upregulation of heme oxygenase (HO)-1 cytoprotective protein, and release of interleukin (IL)-10 anti-inflammatory cytokine; IL-10 is then linked in a positive feedback loop to further CD163 expression. The potency of this M1/M2 switching pathway is underscored by the fact that human Hp2 polymorphisms are associated with worsened clinical outcomes for diabetic complications, including DN. Parallel observations in animals show that HO-1 activation by hemin protects against DN in rodent models of diabetes. This review discusses the concept that Nrf2/HO-1 acts as a 'therapeutic funnel' through which a range of natural and synthetic anti-oxidants may drive M1 to M2 switching and improved kidney function in diabetes. We also discuss our observations on the evolution of M1/M2 phenotypes in a human model of wound healing which has presented intriguing potential drug targets for DN, such as eotaxin/CCR3.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Macrófagos/classificação , Macrófagos/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacosRESUMO
The CCAS EXPERT SUMMIT convened an array of international experts in Barbados on August 27-31, 2017 under the theme "From Care to Cure-Shifting the HIV Paradigm." The Caribbean Cytometry & Analytical Society (CCAS) partnered with the Joint United Nations Programme on HIV/AIDS (UNAIDS) to deliver a program that reviewed the advances in antiretroviral therapy and the public health benefits accruing from treatment as prevention. Particular emphasis was placed on reexamining stigma and discrimination through a critical appraisal of whether public health messaging and advocacy had kept pace with the advances in medicine. Persistent fear of HIV driving discriminatory behavior was widely reported in different regions and sectors, including the healthcare profession itself; continued fear of the disease was starkly misaligned with the successes of new medical treatments and progress toward the UNAIDS 90-90-90 targets. The summit therefore adopted the mantra "Test-Treat-Defeat" to help engage with the public in a spirit of optimism aimed at creating a more conducive environment for persons to be tested and treated and, thereby, help reduce HIV disease and stigma at the individual and community levels.
Assuntos
Antirretrovirais/uso terapêutico , Quimioprevenção/métodos , Gerenciamento Clínico , Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/tratamento farmacológico , Barbados , Feminino , Infecções por HIV/prevenção & controle , Humanos , Masculino , Sociedades CientíficasAssuntos
Diabetes Mellitus Tipo 2/complicações , Pé Diabético/complicações , Doenças Hereditárias Autoinflamatórias/genética , Receptores do Fator de Necrose Tumoral/genética , Cicatrização/fisiologia , Alelos , Amputação Cirúrgica , Feminino , Febre , Pé/cirurgia , Humanos , Perna (Membro)/cirurgia , Ossos do Metatarso , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) into the intravascular space. FHb participates in redox reactions creating various reactive oxygen species which rapidly and irreversibly scavenge nitric oxide, thereby attenuating its vasodilatory, antithrombotic, and anti-inflammatory properties. FHb also induces endothelial expression of adhesion molecules, triggering leukocyte margination at the vessel wall. These mechanisms participate in diverse SCD-associated clinical events including nephropathy, pulmonary hypertension, chronic leg ulceration, and ischemic events. FHb also exerts a direct reno-toxic effect contributing to albuminuria which is an early, frequent manifestation of glomerular injury. Under normal conditions, fHb is effectively scavenged by the Hb-scavenging mechanism (HSM); this involves binding to haptoglobin (Hp), uptake via the Hb-scavenging receptor (CD163) on monocytes and metabolism by heme-oxygenase-1. This culminates in increased CD163 expression and release of anti-inflammatory by-products e.g. interleukin-10 (IL-10). In SCD, the Hb-binding capacity is overwhelmed by chronic hemolysis; our previous research shows serum Hp as the depleted component. This deficiency could result in the harmful consequences of circulating fHb going unbridled. The hypothesis we explore here is that Hp infusions, in excess of fHb concentration, will allow the HSM to remain functional, and thereby achieve improved clinical outcomes, tracking albuminuria as a sentinel. Albuminuria was selected because of its high prevalence in SCD and its relative ease of diagnosis and monitoring. The hypothesis may be evaluated in four phases: Phase 1 will determine the concentration of Hp needed to trigger the HSM as measured by induction of CD163 and IL-10 and the recovery of hemopexin. Phase 2 will investigate the half-life of HSM induction by analyzing the time-course of CD163 expression and IL-10 and hemopexin serum concentration. Phase 3 will determine patient eligibility for therapy, whether as treatment or prevention. Phase 4 will test the efficacy of Hp transfusions in a randomized control trial as measured by correction of albuminuria. Angiotensin converting enzyme inhibitors (ACEi) are currently the first-line treatment for SCD nephropathy, however hyperkalemia limits its use. Hydroxyurea, which has therapeutic value in many SCD adverse events, has yielded inconsistent effects on albuminuria. We are proposing the addition of an intervention more proximal in the hemolytic cascade. Boosting the exhausted Hb-scavenging capacity via Hp replacement therapy has the potential to modify multiple downstream clinical events.
Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/prevenção & controle , Haptoglobinas/administração & dosagem , Haptoglobinas/uso terapêutico , Albuminúria/diagnóstico , Anti-Inflamatórios , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Criança , Pré-Escolar , Hemoglobinas/uso terapêutico , Hemólise , Hemopexina/metabolismo , Humanos , Hidroxiureia/uso terapêutico , Infusões Intravenosas , Interleucina-10/metabolismo , Modelos Teóricos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Superfície Celular/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Comprehensive care in homozygous sickle cell disease (HbSS) entails universal neonatal screening and subsequent monitoring of identified patients, a process which has been streamlined in the neighbouring island of Jamaica. In preparation for a similar undertaking in Barbados, we have developed a database of persons with known HbSS, and have piloted processes for documenting clinical manifestations. We now present a brief clinical profile of these findings with comparisons to the Jamaican cohort. METHODS: HbSS participants were recruited from clinics and support groups. A history of select clinical symptoms was taken and blood and urine samples and echocardiograms were analysed. A re-analysis of data from a previous birth cohort was completed. RESULTS: Forty-eight persons participated (32 F/16 M); age range 10-62 yrs. 94% had a history of ever having a painful crisis. In the past year, 44% of participants had at least one crisis. There were >69 crises in 21 individuals; 61% were self-managed at home and the majority of the others were treated and discharged from hospital; few were admitted. The prevalence of chronic leg ulceration was 27%. Forty-two persons had urinalysis, 44% were diagnosed with albuminuria (urinary protein/creatinine ratio ≥30 mg/g). Thirty-two participants had echocardiography, 28% had a TRJV ≥ 2.5 m/s. Re-analysis of the incidence study revealed a sickle gene frequency (95% CI) of 2.01% (0.24 to 7.21). CONCLUSION: Although we share a common ancestry, it is thought that HbSS is less common and less severe in Barbados compared to Jamaica. The Jamaican studies reported a sickle gene frequency of 3.15 (2.81 to 3.52); the prevalence of chronic leg ulcers and albuminuria was 29.5% and 42.5% respectively. These comparisons suggest that our initial thoughts may be speculative and that HbSS may be an underestimated clinical problem in Barbados. A prospective neonatal screening programme combined with centralized, routine monitoring of HbSS morbidity and outcomes will definitively answer this question and will improve the evidence-based care and management of HbSS in Barbados.
Assuntos
Anemia Falciforme/diagnóstico , Programas de Rastreamento/métodos , Vigilância da População/métodos , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Barbados/epidemiologia , Criança , Estudos de Coortes , Comorbidade , Feminino , Homozigoto , Humanos , Recém-Nascido , Jamaica/epidemiologia , Úlcera da Perna/diagnóstico , Úlcera da Perna/epidemiologia , Masculino , Pessoa de Meia-Idade , Triagem Neonatal/métodos , Projetos Piloto , Adulto JovemRESUMO
In Barbados, use of the Systemic Lupus Erythematosus (SLE) Disease Activity Index (SLEDAI) is limited by the unavailability of serologic markers. The SLE Activity Questionnaire (SLAQ) excludes laboratory measurements and is therefore more accessible. Here, we investigate the agreement between the SLAQ, the SLEDAI, and the physician global assessment (PGA). A pilot of 32 participants completed the SLAQ and SLEDAI. The tools were compared (1) in their original format, (2) limited to common indices, and (3) limited to the same patient recall period. We compared the proportions of persons reporting disease activity and the concordance between calculated activity scores for SLAQ versus SLEDAI and for SLAQ versus PGA. Seventy-eight percent versus 59% of participants reported disease activity with the original SLEDAI versus SLAQ, respectively. The relationship was reversed to 22% versus 59% when the matched item tools were compared. Concordance was 0.62 (95% CI 0.42-0.81) between the original scores, 0.70 (0.57-0.83) when restricted by matched items, and 0.72 (0.59-0.84) when further restricted by recall period. Concordance between the SLAQ and PGA was 0.56 (0.32-0.80). Reversal of the disease activity percentage in the matched items comparison highlights the inadequacy of tools that exclude laboratory measurements and suggests that the subjective nature of SLAQ may contribute to over-reporting. Further work is needed to produce a robust disease activity tool apt for resource-constrained environments.
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BACKGROUND: Intravascular hemolysis may cause tissue injury directly or via a systemic inï¬ammatory response. Under physiological conditions, extracorpuscular hemoglobin (Hb) is bound by haptoglobin(Hp) and the complex internalized via the hemoglobin scavenger receptor CD163 on monocytes, prior to catabolism via heme-oxygenase-1 (HO-1). Recently, a novel subset of CD68(pos)CD163(high)HLA-DR(low) macrophages with high expression of HO-1 was recognized in hemorrhagic areas of atherosclerotic plaques, distinct from CD68(pos)CD163(low)HLA-DR(high) foam cell macrophages with low- HO-1 content. Considering the hemolytic insult during CPB, we hypothesized that an equivalent compensatory CD163(high)HLA-DR(low) phenotype will evolve in circulating CD14(pos) monocytes post surgery. METHODS: Twelve patients undergoing elective surgery with CPB were enrolled with informed consent.Whole-blood samples were collected in EDTA at predetermined time-points, pre- intra-, and postoperatively. Whole-blood was evaluated by three-color flow cytometry for expression of CD14, CD163, and HLA-DR; CD14(pos) cells were also permeabilized to detect intracellular HO-1 protein. Plasma [Hp-Hb] concentration was determined by ELISA. RESULTS: A striking phenotypic switch from CD163(low)HLA-DR(high) preoperatively to CD163(high)HLA-DR(low) postoperatively at 24 h was observed on circulating CD14(pos) monocytes. Intracellular HO-1 protein was also significantly up-regulated at 24 h after declamping. These phenotypic changes were preceded by peak Hb-Hp levels observed at 2 h. CONCLUSION: We have shown for the first time, a phenotypic commitment of monocytes towards a protective CD14(pos)CD163(high)HLA-DR(low) population with increased intracellular HO-1 occurring in the circulation during the recovery phase of CPB. These findings have implications for monitoring of anti-inflammatory interventions and linkage to clinical outcomes.