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OBJECTIVES: Identifying whether a country is ready to deploy a new vaccine or improve uptake of an existing vaccine requires knowledge of a diverse range of interdependent, context-specific factors. This scoping review aims to identify common themes that emerge across articles, which include tools or guidance that can be used to establish whether a country is ready to deploy a new vaccine or increase uptake of an underutilised vaccine. DESIGN: Scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: Embase, CINAHL, Cochrane Library, Google Scholar, MEDLINE, PsycINFO and Web of Science were searched for articles published until 9 September 2023. Relevant articles were also identified through expert opinion. ELIGIBILITY CRITERIA: Articles published in any year or language that included tools or guidance to identify factors that influence a country's readiness to deploy a new or underutilised vaccine. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis. RESULTS: 38 articles met our inclusion criteria; these documents were created using methodologies including expert review panels and Delphi surveys and varied in terms of content and context-of-use. 12 common themes were identified relevant to a country's readiness to deploy a new or underutilised vaccine. These themes were as follows: (1) legal, political and professional consensus; (2) sociocultural factors and communication; (3) policy, guidelines and regulations; (4) financing; (5) vaccine characteristics and supply logistics; (6) programme planning; (7) programme monitoring and evaluation; (8) sustainable and integrated healthcare provision; (9) safety surveillance and reporting; (10) disease burden and characteristics; (11) vaccination equity and (12) human resources and training of professionals. CONCLUSIONS: This information has the potential to form the basis of a globally applicable evidence-based vaccine readiness assessment tool that can inform policy and immunisation programme decision-makers.
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Vacinas , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/provisão & distribuição , VacinaçãoRESUMO
Visual assessment is currently used for primary screening or triage of screen-positive individuals in cervical cancer screening programs. Most guidelines recommend screening and triage up to at least age 65 years old. We examined cervical images from participants in three National Cancer Institute funded cervical cancer screening studies: ALTS (2864 participants recruited between 1996 to 1998) in the United States (US), NHS (7548 in 1993) in Costa Rica, and the Biopsy study (684 between 2009 to 2012) in the US. Specifically, we assessed the visibility of the squamocolumnar junction (SCJ), which is the susceptible zone for precancer/cancer by age, as reported by colposcopist reviewers either at examination or review of cervical images. The visibility of the SCJ declined substantially with age: by the late 40s the majority of people screened had at most partially visible SCJ. On longitudinal analysis, the change in SCJ visibility from visible to not visible was largest for participants from ages 40-44 in ALTS and 50-54 in NHS. Of note, in the Biopsy study, the live colposcopic exam resulted in significantly higher SCJ visibility as compared to review of static images (Weighted kappa 0.27 (95% Confidence Interval: 0.21, 0.33), Asymmetry chi-square P-value<0.001). Lack of SCJ visibility leads to increased difficulty in diagnosis and management of cervical precancers. Therefore, cervical cancer screening programs reliant on visual assessment might consider lowering the upper age limit for screening if there are not adequately trained personnel and equipment to evaluate and manage participants with inadequately visible SCJ.
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Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/patologia , Detecção Precoce de Câncer/métodos , Displasia do Colo do Útero/patologia , BiópsiaRESUMO
Cervical cancer screening and treatment of screen positives is an important and effective strategy to reduce cervical cancer morbidity and mortality. In order to have an accurate cervical cancer screening and evaluation of positives, the entire Squamocolumnar Junction (SCJ) must be visible. Throughout the life course, the position of the SCJ changes and affects its visibility. SCJ visibility was analyzed among participants screened at the League Against Cancer Clinic in Lima, Peru. Of the 4247 participants screened, the SCJ was fully visible in 49.7% of participants, partially visible in 23.1%, and not visible in 27.2%. Visibility decreased with age, and by age 45 years old, the SCJ was not fully visible in over 50% of participants. Our results show that a high percentage of participants at ages still recommended for screening do not have totally visible SCJ, and we may need to reconsider the upper age limit for screening and find new strategies for evaluation of those with a positive screening test and non-visible SCJ.
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Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Detecção Precoce de Câncer , Peru , Programas de RastreamentoRESUMO
Cervical cancer screening and management in the U.S. has adopted a risk-based approach. However, the majority of cervical cancer cases and deaths occur in resource-limited settings, where screening and management are not widely available. We describe a conceptual model that optimizes cervical cancer screening and management in resource-limited settings by utilizing a risk-based approach. The principles of risk-based screening and management in resource limited settings include (1) ensure that the screening method effectively separates low-risk from high-risk patients; (2) directing resources to populations at the highest cancer risk; (3) screen using HPV testing via self-sampling; (4) utilize HPV genotyping to improve risk stratification and better determine who will benefit from treatment, and (5) automated visual evaluation with artificial intelligence may further improve risk stratification. Risk-based screening and management in resource limited settings can optimize prevention by focusing triage and treatment resources on the highest risk patients while minimizing interventions in lower risk patients.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer/métodos , Região de Recursos Limitados , Inteligência Artificial , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Programas de Rastreamento/métodosRESUMO
BACKGROUND: Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010-2021 about Madagascar's MIP activities and to identify barriers and facilitators to MIP interventions uptake. METHODS: PubMed, Google Scholar, and USAID's files (Development Experience Catalog) were searched using the terms "Madagascar AND pregnancy AND malaria," and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database. RESULTS: Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women's KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier. CONCLUSION: Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings.
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Antimaláricos , Malária , Complicações Parasitárias na Gravidez , Feminino , Gravidez , Humanos , Antimaláricos/uso terapêutico , Madagáscar , Malária/prevenção & controle , Malária/tratamento farmacológico , Pirimetamina/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Cuidado Pré-Natal , Complicações Parasitárias na Gravidez/prevenção & controle , Complicações Parasitárias na Gravidez/tratamento farmacológico , Combinação de MedicamentosRESUMO
INTRODUCTION: Prophylactic human papillomavirus (HPV) vaccines have been shown to be highly effective in protecting women against cervical infections, high-grade abnormalities and cancer caused by the targeted HPV types. However, the evidence for their effectiveness in women living with HIV (WLWH) is less clear. METHODS: WLWH and HIV-negative women who likely did (birth cohorts 1996 and later) and WLWH and HIV(-) negative who likely did not (birth cohorts before 1996) receive HPV vaccination (n=3028; 757 participants for each of the four groups). Between groups, we will compare cervicovaginal, anal and oral prevalent and 6-12 month persistent HPV6/11/16/18 infections as measured using a modified AmpFire HPV genotyping assay that tests for 15 high-risk or intermediate-risk HPV genotypes, HPV6 and HPV11. We will also compare the HPV immune response in HPV-vaccinated WLWH to HPV-vaccinated HIV-negative women using an anti-HPV16 and anti-HPV18 ELISA. Vaccination status will be confirmed through national vaccination records. ANALYSIS: We will calculate point prevalence and prevalence of 6-12 month persisting infections by individual HPV-type specific infections and groups of infections for each anatomic site and for each group of women. Results will be stratified by age at vaccination, age at enrolment and the number of doses (3 vs 2) as well as other factors possibly associated with HPV prevalence. Differences in endpoints between groups, overall and between subgroups, will be tested for statistical significance (p<0.05) using Fisher's exact or Pearson χ2 test. Differences in geometric mean titres and seropositivity will be tested for statistical significance using the Mann-Whitney and Fisher's exact tests, respectively. ETHICS AND DISSEMINATION: The study was approved by the Albert Einstein College of Medicine Institutional Review Board and the Rwanda National Ethics Committee. Results will be disseminated through publication in peer-reviewed journals.
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Infecções por HIV , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Papillomavirus Humano 16/genética , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Ruanda/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , VacinaçãoRESUMO
PURPOSE: Current screening guidelines for prostate cancer (PCa) encourage men to make individual screening decisions after consulting with their primary care provider to weigh the risks and benefits of undergoing prostate specific antigen (PSA) testing, but many men at high risk of PCa diagnosis (notably African American men) are more likely to be uninsured and lack a primary care provider. An academic-community partnership redesigned its community-based screening program to ensure access to services for African American men, incorporating a session with a trained clinical educator in community settings, designed to increase knowledge and promote informed decision-making regarding PSA testing. This study evaluated effects of the intervention on decision-making outcomes. METHODS: To evaluate program efficacy, 88 men completed pre- and post-test surveys assessing outcomes of interest. RESULTS: Participants' knowledge, beliefs, attitudes, anxiety levels, and self-efficacy all improved from pre- to post-test at a statistically significant level. Most notably participants' awareness that PCa is often not life-threatening, and watchful waiting is a reasonable treatment option increased after the encounter. More than half of the study sample felt they had received enough knowledge to make an informed decision about whether the PSA test was right for them. CONCLUSION: Our findings show the program had positive effects on men's ability to make informed decisions about PCa screening and demonstrate that educational outreach programs with an emphasis on informed decision-making can effectively balance screening guidelines with the needs of underserved populations in community settings to improve outcomes.
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Antígeno Prostático Específico , Neoplasias da Próstata , Negro ou Afro-Americano , Tomada de Decisões , Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Programas de Rastreamento , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapiaRESUMO
Large household surveys performed to estimate coverage rates for various health interventions, including intermittent preventive treatment, depend on recall. Many studies question the validity of recalled data. Regarding vaccine coverage rates, it is standard practice to validate responses using medical history cards. To validate the coverage rates of intermittent preventive treatment during pregnancy reported by large household surveys, recalled coverage rates were compared with antenatal care card data in Benin, Ghana, Malawi, and Tanzania. The results indicated that recall was comparable to the coverage rates provided indicated by the antenatal care cards. These findings suggest that intermittent preventive treatment coverage rates reported by large household surveys performed using recalled data are valid.
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Malária/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Adulto , Antimaláricos/uso terapêutico , Benin , Feminino , Gana , Humanos , Malária/tratamento farmacológico , Malaui , Gravidez , Cuidado Pré-Natal/métodos , TanzâniaRESUMO
BACKGROUND: Both bipolar disorder and major depressive disorder are characterized by difficulties in emotion regulation. Little is known about which specific emotion regulatory patterns may be transdiagnostic versus disorder specific, and how such patterns change as a function of current mood states. METHODS: This preliminary investigation examined specific patterns of self-reported trait emotion regulation difficulties and mindfulness-based regulations strategies across four groups: remitted adults with bipolar I disorder (BD-remitted; n = 32), currently manic adults with bipolar I disorder (BD-manic; n = 19), remitted adults with major depressive disorder (MDD-remitted; n = 32), and healthy controls (CTL; n = 30). RESULTS: All three clinical groups reported significantly greater difficulties with emotion regulation and decreased overall mindfulness-based strategies. CONCLUSIONS: These results suggest that increased emotion regulation difficulties, decreased mindfulness, and increased emotion-driven impulsivity may be transdiagnostic across mood disorders and states, and that impulsivity may be particularly impaired during periods of mania.
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Objective: In 2016 a private Missouri university implemented a campus-wide tobacco-free policy to change social norms and prevent tobacco use among students, staff and faculty. This study assesses impact on tobacco and policy-related perceptions and behaviors. Methods: Before the policy went into effect and again one year later, all university students, staff and faculty were invited to participate in an online survey. Missouri Assessment of College Health Behaviors survey findings supplement results for students. Results: Policy support and norms disapproving tobacco use on campus increased, and self-reported use of any tobacco decreased after the ban was enacted. Conclusions: Our results suggest that the policy led to an increase in the proportion of university community members who agree that smoking on campus is unacceptable, which contributed in turn to a decline in tobacco use on campus, consistent with our theory of effects.
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Política Antifumo , Poluição por Fumaça de Tabaco , Atitude Frente a Saúde , Docentes , Humanos , Prevenção do Hábito de Fumar , Estudantes , Nicotiana , Uso de Tabaco , UniversidadesRESUMO
IMPORTANCE: Given the prevalence of alcohol, cannabis, and tobacco use during adolescence, it is important to explore the relative relationship of these three substances with brain structure. OBJECTIVE: To determine associations between recent alcohol, cannabis, and tobacco use and white and gray matter in a large sample of adolescents. DESIGN, SETTING, AND PARTICIPANTS: MRI data were collected in Nâ¯=â¯200 adolescents ages 14-18 (Mâ¯=â¯15.82â¯years; 67% male; 61% Hispanic/Latino). On average, during the past month, participants reported consuming 2.05 drinks per 1.01 drinking day, 0.64â¯g per 6.98 cannabis use days, and 2.49 cigarettes per 12.32 smoking days. MAIN OUTCOMES AND MEASURES: General linear models were utilized to examine past 30-day average quantities of alcohol, cannabis, and tobacco use, age, sex, and sex by substance interactions in skeletonized white matter (fractional anisotropy and axial, radial, and mean diffusivity) and voxel-based morphometry of gray matter (volume/density). RESULTS: Tobacco use was negatively associated with white matter integrity (radial and mean diffusivity) with peak effects in inferior and superior longitudinal fasciculi. Cannabis use was negatively associated with white matter integrity (axial diffusivity) in a small cluster in the left superior longitudinal fasciculus. No associations were observed between recent alcohol use and white or gray matter overall, but interactions showed significant negative associations between alcohol use and white matter in females. CONCLUSIONS AND RELEVANCE: It is important to note that recent tobacco use, particularly given the popularity of e-tobacco/vaping in this age group, had widespread associations with brain structure in this sample of adolescents.
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Comportamento do Adolescente , Imageamento por Ressonância Magnética/métodos , Uso de Tabaco/patologia , Substância Branca/patologia , Adolescente , Consumo de Bebidas Alcoólicas/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Masculino , Fumar Maconha/patologia , Fatores Sexuais , Consumo de Álcool por Menores , Substância Branca/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this paper is to evaluate a collaborative effort between a health care organization and academic institution to strengthen organizational health literacy. DESIGN/METHODOLOGY/APPROACH: The intervention took place at a rural, federally qualified health clinic in Missouri between May 2009 and April 2011. Qualitative interviews of key informants were conducted before (n=35) and after (n=23) the intervention to examine program implementation and success in effecting organizational change. FINDINGS: Intervention activities helped establish a comprehensive understanding of health literacy. The project achieved moderate, fundamental and sustainable organizational change. The program successfully integrated health literacy practices into clinic systems and garnered leadership and organizational commitment, helped the workforce improve interpersonal communication and embedded practices making health education materials more accessible. ORIGINALITY/VALUE: The study points to programmatic, conceptual and methodological challenges that must be addressed for organizations to improve health literacy practices, and suggests change management strategies to advance organizational health literacy.
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Letramento em Saúde , Cultura Organizacional , Serviços de Saúde Rural , Comportamento Cooperativo , Atenção à Saúde , Humanos , Entrevistas como Assunto , Missouri , Estudos de Casos Organizacionais , Pesquisa Qualitativa , UniversidadesRESUMO
Adolescence is a neurodevelopmental period of heightened sexual risk taking. Neuroimaging can help elucidate crucial neurocognitive mechanisms underlying adolescent sexual risk behavior, yet few empirical studies have investigated this neural link. To address this gap in the literature, we examined the association between neurocognitive function during response inhibition-a known correlate of risk behaviors-and frequency of intercourse without a condom among adolescents. We examined the correlation between condom use and fMRI-based Stroop response in a large ethnically diverse sample of high-risk adolescents (n = 171). Partially replicating previous literature, sexual risk was positively correlated with blood-oxygen-level-dependent (BOLD) activation in the middle frontal gyrus during response inhibition, highlighting the relevance of this region during risky sexual decision making within this age group.
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Comportamento do Adolescente/psicologia , Cognição/fisiologia , Rede Nervosa/diagnóstico por imagem , Comportamento Sexual/psicologia , Adolescente , Comportamento do Adolescente/etnologia , Preservativos/estatística & dados numéricos , Tomada de Decisões/fisiologia , Feminino , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiologia , Assunção de Riscos , Comportamento Sexual/etnologiaRESUMO
Starting school later, keeping adolescents busy with structured programming, and making free condoms available, as Steinberg (2015) suggests, are important and necessary steps, but they are simply not sufficient if the goal is reducing sexually transmitted infections and unplanned pregnancy. We agree that the current state of affairs, which in many schools involves sexuality education using programs that are not empirically supported, is unacceptable. However, abandoning sexuality education entirely would leave adolescents ill equipped to protect themselves. Despite the fact that current intervention technology is neither perfect nor optimally effective, there are empirically supported, school-based sexual risk reduction interventions that teach these skills and are readily available. In addition, even though we agree that structured afternoon programs for school-aged adolescents would reduce the opportunity for sexual risk behavior during the school years, such programs would not address the demographic reality of sexual risk that continues for adolescents and emerging adults far past the end of traditional secondary education. We believe Steinberg's suggestions are an excellent start and ought to be implemented. But complementary to this approach should be the use of existing empirically supported sexual risk reduction interventions and research into the development of even more effective interventions.
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Comportamento do Adolescente/psicologia , Comportamento de Redução do Risco , Assunção de Riscos , Educação Sexual/normas , Comportamento Sexual/psicologia , Adolescente , HumanosRESUMO
Despite studies showing the relevance of different decision-making abilities, including response inhibition, to likelihood of using substances during adolescence, few have examined these neural processes among high-risk, substance-using youth. The current study explored associations between alcohol and marijuana use and functional activation differences during Stroop performance among a large sample (N=80) of ethnically-diverse, high-risk youth in an fMRI-based task. In the absence of associations between substance use and task behavioral performance, adolescents with greater alcohol use showed less activation during the more cognitively difficult portion of the task across clusters in bilateral cuneus and precuneus, and right and left superior temporal gyrus. No associations were observed with marijuana use. The current results may suggest neural patterns of deactivation in regions important for cognitive control, such that alcohol use may confer additional risk for future decreased inhibition among these high-risk adolescents. The ability to inhibit prepotent responses has been shown to predict later response to treatment, and early interventions to encourage further development of cognitive control could represent promising options for treatment.
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Consumo de Bebidas Alcoólicas/fisiopatologia , Inibição Psicológica , Fumar Maconha/fisiopatologia , Lobo Parietal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Relacionados ao Uso de Substâncias/psicologia , Análise e Desempenho de TarefasRESUMO
People with schizophrenia are impaired at organizing potentially ambiguous visual information into well-formed shape and object representations. This perceptual organization (PO) impairment has not been found in other psychiatric disorders. However, recent data on body dysmorphic disorder (BDD), suggest that BDD may also be characterized by reduced PO. Similarities between these groups could have implications for understanding the RDoC dimension of visual perception in psychopathology, and for modeling symptom formation across these two conditions. We compared patients with SCZ (n=24) to those with BDD (n=20), as well as control groups of obsessive-compulsive disorder (OCD) patients (n=20) and healthy controls (n=20), on two measures of PO that have been reliably associated with schizophrenia-related performance impairment. On both the contour integration and Ebbinghaus illusion tests, only the SCZ group demonstrated abnormal performance relative to controls; the BDD group performed similarly to the OCD and CON groups. In addition, on both tasks, the SCZ group performed more abnormally than the BDD group. Overall, these data suggest that PO reductions observed in SCZ are not present in BDD. Visual processing impairments in BDD may arise instead from other perceptual disturbances or attentional biases related to emotional factors.
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Transtornos Dismórficos Corporais/psicologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Percepção Visual , Adulto , Atenção , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de ModelosRESUMO
BACKGROUND: Bipolar disorder is characterized by impairments in cognitive functioning, both during acute mood episodes and periods of euthymia, which interfere with functioning. Cognitive functioning is typically assessed using laboratory-based tests, which may not capture how cognitive dysfunction is experienced in real-life settings. Little is known about the specific illness characteristics of bipolar disorder that contribute to cognitive dysfunction in everyday life. METHODS: Participants met DSM-IV criteria for bipolar I disorder (n = 68) in a depressed or euthymic state. Everyday executive functioning was evaluated using the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Frontal Systems Behavior Rating Scale (FrSBe). Participants completed clinician rated measures of mood state (Hamilton Depression Rating Scale, Young Mania Rating Scale), prior illness course and co-morbidities (Mini International Neuropsychiatric Interview), as well as self-report measures of psychotropic medication use and medical co-morbidity. RESULTS: Individuals in this study reported significant impairment in every domain of executive functioning. These deficits were associated with a multitude of illness factors, some directly impacted by mood symptoms and others shaped by illness chronicity, psychiatric comorbidity, medical co-morbidity, and medication use. DISCUSSION: Executive functioning problems observed in everyday functioning in bipolar disorder are not entirely mood-state dependent. Cognitive rehabilitation for executive dysfunction should be considered an important adjunctive treatment for many individuals with bipolar disorder.