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1.
Int J Eat Disord ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34761418

RESUMO

OBJECTIVE: Growing evidence suggests that subjective binge eating (SBE; loss of control eating involving subjectively, but not objectively, large quantities of food) is clinically concerning even though it is not currently considered a diagnostic criterion for eating disorders. However, the lived experience of SBEs has not been examined in a systematic, and data-driven way. METHOD: The current study used a qualitative, inductive interview approach to further define SBEs as described by individuals who experience them. Participants (N = 14; 11 cisgender women, Mage  = 35.29, 12 White/non-Latinx) reported SBEs that occurred at least twice per week over the prior 3 months. We completed semi-structured qualitative phone interviews with participants regarding their most recent SBE and objective binge-eating episode (OBE) if applicable, as well as broader experiences and attitudes regarding non-binge eating. RESULTS: Inductive, reflexive, thematic coding yielded descriptive and interpretive codes regarding SBEs. Main themes regarding SBE experience included: (a) SBEs Occur Across Contexts and Food Types, (b) SBEs Are Contrasts to General Over-Control, (c) SBEs Are Distress- and Disconnection-Inducing, Not Relieving, (d) SBEs Are Responses to Hunger and Restriction, and (e) SBEs Can Be "Echoes" of OBEs. DISCUSSION: The current study explored the lived experiences of those who report SBEs and provides an important foundation for hypothesis generation for future research on and clinical interventions for SBEs.

2.
J Clin Oncol ; 39(33): 3693-3704, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34516759

RESUMO

PURPOSE: Despite extensive randomized evidence supporting the use of treatment breaks in metastatic colorectal cancer (mCRC), they are not universally offered to patients despite improvements in quality of life without detriment to overall survival (OS). FOCUS4-N was set up to explore the impact of oral maintenance therapy in patients who are responding to first-line therapy. METHODS: FOCUS4 was a molecularly stratified trial program that registered patients with newly diagnosed mCRC. The FOCUS4-N trial was offered to patients in whom a targeted subtrial was unavailable or biomarker tests failed. Patients were randomly assigned using a 1:1 ratio between maintenance capecitabine and active monitoring (AM). The primary outcome was progression-free survival (PFS) with secondary outcomes including OS toxicity and tolerability. RESULTS: Between March 2014 and March 2020, 254 patients were randomly assigned (127 to capecitabine and 127 to AM) across 88 UK sites. Baseline characteristics were balanced. There was strong evidence of efficacy for PFS (hazard ratio = 0.40; 95% CI, 0.21 to 0.75; P < .0001), but no significant improvement in OS (hazard ratio, 0.93; 95% CI, 0.69 to 1.27; P = .66) was observed. Compliance with treatment was good, and toxicity from capecitabine versus AM was as expected with grade ≥ 2 fatigue (25% v 12%), diarrhea (23% v 13%), and hand-foot syndrome (26% v 3%). Quality of life showed little difference between the groups. CONCLUSION: Despite strong evidence of disease control with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for mCRC. Capecitabine without bevacizumab may be used to extend PFS in the interval after 16 weeks of first-line therapy.

3.
J Clin Oncol ; 39(33): 3705-3715, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34538072

RESUMO

PURPOSE: Outcomes in RAS-mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition. METHODS: Patients with newly diagnosed mCRC were registered into FOCUS4 and tested for TP53 and RAS mutations. Those with both mutations who were stable or responding after 16 weeks of chemotherapy were randomly assigned 2:1 between adavosertib and active monitoring (AM). Adavosertib (250 mg or 300 mg) was taken orally once on days 1-5 and days 8-12 of a 3-week cycle. The primary outcome was progression-free survival (PFS), with a target hazard ratio (HR) of 0.5 and 80% power with a one-sided 0.025 significance level. RESULTS: FOCUS4-C was conducted between April 2017 and Mar 2020 during which time 718 patients were registered; 247 (34%) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib = 44; AM = 25). Adavosertib was associated with a PFS improvement over AM (median 3.61 v 1.87 months; HR = 0.35; 95% CI, 0.18 to 0.68; P = .0022). Overall survival (OS) was not improved with adavosertib versus AM (median 14.0 v 12.8 months; HR = 0.92; 95% CI, 0.44 to 1.94; P = .93). In prespecified subgroup analysis, adavosertib activity was greater in left-sided tumors (HR = 0.24; 95% CI, 0.11 to 0.51), versus right-sided (HR = 1.02; 95% CI, 0.41 to 2.56; interaction P = .043). Adavosertib was well-tolerated; grade 3 toxicities were diarrhea (9%), nausea (5%), and neutropenia (7%). CONCLUSION: In this phase II randomized trial, adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53-mutant mCRC. Further testing is required in this sizable population of unmet need.

4.
Nature ; 596(7873): 597-602, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34408320

RESUMO

ADP-ribosyltransferases use NAD+ to catalyse substrate ADP-ribosylation1, and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria2-4. Reversible ADP-ribosylation has traditionally been considered a protein-specific modification5, but recent in vitro studies have suggested nucleic acids as targets6-9. Here we present evidence that specific, reversible ADP-ribosylation of DNA on thymidine bases occurs in cellulo through the DarT-DarG toxin-antitoxin system, which is found in a variety of bacteria (including global pathogens such as Mycobacterium tuberculosis, enteropathogenic Escherichia coli and Pseudomonas aeruginosa)10. We report the structure of DarT, which identifies this protein as a diverged member of the PARP family. We provide a set of high-resolution structures of this enzyme in ligand-free and pre- and post-reaction states, which reveals a specialized mechanism of catalysis that includes a key active-site arginine that extends the canonical ADP-ribosyltransferase toolkit. Comparison with PARP-HPF1, a well-established DNA repair protein ADP-ribosylation complex, offers insights into how the DarT class of ADP-ribosyltransferases evolved into specific DNA-modifying enzymes. Together, our structural and mechanistic data provide details of this PARP family member and contribute to a fundamental understanding of the ADP-ribosylation of nucleic acids. We also show that thymine-linked ADP-ribose DNA adducts reversed by DarG antitoxin (functioning as a noncanonical DNA repair factor) are used not only for targeted DNA damage to induce toxicity, but also as a signalling strategy for cellular processes. Using M. tuberculosis as an exemplar, we show that DarT-DarG regulates growth by ADP-ribosylation of DNA at the origin of chromosome replication.

5.
Clin Child Psychol Psychiatry ; 26(4): 1124-1136, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34237236

RESUMO

Binge eating (BE) often develops during adolescence and is associated with deleterious psychological and physical consequences. Current treatments for adolescents achieve suboptimal results, likely due to failure to adequately address fear of weight gain (FOWG) which maintains BE. Thus, exposure treatment (the most powerful intervention for fear) may be a promising approach. However, exposure treatment has only minimally tested in adults with BE and never tested in adolescents. Thus, the current study is the first to evaluate a 4-session exposure module within a 12-session standard cognitive behavioral therapy for adolescents with BE. We recruited adolescents with BE (N = 5) and examined treatment feasibility, acceptability, and preliminary effects on FOWG and eating pathology. Overall, the 4-session exposure module was feasible and acceptable and showed preliminary evidence that it could reduce FOWG. However, several participants did not endorse significant fears of weight gain; rather, these participants reported that fears of deprivation or social judgment were more related to their BE. Future research should test higher doses of exposure and further examine the role of fear of deprivation/social judgment. Finally, future iterations of this treatment could include more parent involvement or test exposure in combination with treatments other than cognitive behavioral therapy, such as family-based treatment.


Assuntos
Transtorno da Compulsão Alimentar , Terapia Cognitivo-Comportamental , Adolescente , Adulto , Transtorno da Compulsão Alimentar/terapia , Medo , Humanos , Resultado do Tratamento
6.
Behav Ther ; 52(2): 465-477, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33622514

RESUMO

We examined the outcomes of individual cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) in a sample of 93 adults seeking treatment in a university outpatient clinic specializing in CBT for SAD. Treatment followed the structure of a manual, but number of sessions varied according to client needs. After approximately 20 weeks of therapy, patients' social anxiety had decreased and their quality of life had increased. Patients with more severe SAD or comorbid major depressive disorder (MDD) at pretreatment demonstrated higher levels of social anxiety averaged across pre- and posttreatment. However, clinician-rated severity of SAD, comorbid MDD, or comorbid generalized anxiety disorder did not predict treatment outcome. Higher pretreatment scores on measures of safety behaviors and cognitive distortions were associated with higher social anxiety averaged across pre- and posttreatment and predicted greater decreases from pre- to posttreatment on multiple social anxiety outcome measures. We found no predictors of change in quality of life. Those with high levels of safety behaviors and distorted cognitions may benefit more from CBT, perhaps due to its emphasis on targeting avoidance through exposure and changing distorted thinking patterns through cognitive restructuring methods. Our study lends support to the body of research suggesting that manualized CBT interventions can be applied flexibly in clinical settings with promising outcomes for patients over a relatively short course of therapy.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior , Fobia Social , Adulto , Transtorno Depressivo Maior/terapia , Humanos , Fobia Social/terapia , Qualidade de Vida , Resultado do Tratamento
7.
J Anxiety Disord ; 78: 102362, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33486385

RESUMO

INTRODUCTION: Individuals with social anxiety disorder (SAD) are at elevated risk of loneliness, yet little research has examined loneliness in this population. Cognitive-behavioral group therapy (CBGT) and mindfulness-based stress reduction (MBSR) have demonstrated efficacy in treating SAD, yet research has not examined whether they lead to reductions in loneliness. METHODS: This sample comprised 108 individuals with SAD who were randomized to CBGT, MBSR, or a waitlist control (WL); WL participants were re-randomized to CBGT or MBSR following WL. Assessments were completed pre- and post-treatment, and 3-, 6-, 9-, and 12-month follow-up assessments. RESULTS: Compared to WL, individuals in CBGT and MBSR were less lonely at post-treatment; there was no difference between treatments after treatment or during follow-up. Greater reductions in social anxiety from pre- to post-treatment predicted lower levels of loneliness during follow-up. Greater reductions in loneliness from pre- to post-treatment also predicted lower levels of social anxiety during follow-up. DISCUSSION: Individuals who experience reductions in their social anxiety during treatment may also feel less lonely following treatment. Reductions in loneliness also lead to improvements in social anxiety. Future research should continue to examine the relationship between social anxiety and loneliness and how interventions for SAD may help reduce loneliness.


Assuntos
Fobia Social , Psicoterapia de Grupo , Ansiedade , Seguimentos , Humanos , Solidão , Fobia Social/terapia , Resultado do Tratamento
8.
Cogn Behav Ther ; 50(5): 351-365, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33084489

RESUMO

Historically, cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) has been evaluated in randomized-controlled trials as a 12-16 session treatment and has demonstrated response rates ranging from 58% to 75%. Despite these promising results, some patients do not improve substantially after this short course of CBT. It is unclear whether non-responding patients would make substantial improvements in social anxiety with further treatment. In a university outpatient clinic specializing in CBT for SAD, we compared outcomes for patients who ended treatment after approximately 20 sessions of CBT (n = 38) to those who continued treatment for a variable number of additional sessions (n = 34). We found no between-group differences in demographic characteristics, number of comorbid diagnoses, comorbid generalized anxiety disorder or major depressive disorder, or severity of depression at baseline. Patients who ended treatment after 20 sessions experienced greater improvements in SAD over those 20 sessions compared to those who continued treatment. Both groups experienced changes in depression and quality of life over the first 20 sessions. Those who continued treatment showed additional decreases in social anxiety beyond session 20. For those who initially appear to be non-responsive to CBT for SAD, a longer course of treatment may elicit significant improvements.


Assuntos
Terapia Cognitivo-Comportamental , Fobia Social/psicologia , Fobia Social/terapia , Adulto , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Masculino , Fobia Social/complicações , Qualidade de Vida , Resultado do Tratamento
9.
Ann Am Thorac Soc ; 18(7): 1191-1201, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33326348

RESUMO

Rationale: Breakdowns in clinician-family communication in intensive care units (ICUs) are common, yet there are no easily scaled interventions to prevent this problem.Objectives: To assess the feasibility, usability, acceptability, and perceived effectiveness of a communication intervention that pairs proactive family meetings with an interactive, web-based tool to help surrogates prepare for clinician-family meetings.Methods: We conducted a two-arm, single-blind, patient-level randomized trial comparing the Family Support Tool with enhanced usual care in two ICUs in a tertiary-care hospital. Eligible participants included surrogates of incapacitated patients judged by their physicians to have ≥40% risk of death or severe long-term functional impairment. The intervention group received unlimited tool access, with prompts to complete specific content upon enrollment and before two scheduled family meetings. Before family meetings, research staff shared with clinicians a one-page summary of surrogates' main questions, prognostic expectations, beliefs about the patient's values, and attitudes about goals of care. The comparator group received usual care enhanced with scheduled family meetings. Feasibility outcomes included the proportion of participants who accessed the tool before the first family meeting, mean number of logins, and average tool engagement time. We assessed tool usability with the System Usability Scale, assessed tool acceptability and perceived effectiveness with internally developed questionnaires, and assessed quality of communication and shared decision-making using the Quality of Communication questionnaire.Results: Of 182 screened patients, 77 were eligible. We enrolled 52 (67.5%) patients and their primary surrogate. Ninety-six percent of intervention surrogates (24/25) accessed the tool before the first family meeting (mean engagement time, 62 min ± 27.7) and logged in 4.2 times (±2.1) on average throughout the hospitalization. Surrogates reported that the tool was highly usable (mean, 82.4/100), acceptable (mean, 4.5/5 ± 0.9), and effective (mean, 4.4/5 ± 0.2). Compared with the control group, surrogates who used the tool reported higher overall quality of communication (mean, 8.9/10 ± 1.6 vs. 8.0/10 ± 2.4) and higher quality in shared decision-making (mean, 8.7/10 ± 1.5 vs. 8.0/10 ± 2.4), but the difference did not reach statistical significance.Conclusions: It is feasible to deploy an interactive web-based tool to support communication and shared decision-making for surrogates in ICUs. Surrogates and clinicians rated the tool as highly usable, acceptable, and effective.


Assuntos
Estado Terminal , Relações Profissional-Família , Tomada de Decisões , Humanos , Unidades de Terapia Intensiva , Internet , Projetos Piloto , Método Simples-Cego
10.
Body Image ; 36: 185-192, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33360475

RESUMO

Higher weight individuals experience frequent weight-related discrimination, which is associated with exercise avoidance. Exercise is a health behavior with multiple physical and mental health benefits and should be accessible to all. The current study examined another factor that might influence exercise in addition to weight stigma: social anxiety (SA). Given the often public nature of exercise, individuals with SA may feel scrutinized when exercising, which may lead to avoidance. This study examined whether SA moderates the relationship between body mass index (BMI) and exercise and whether SA and its interaction with BMI predict exercise behavior after accounting for weight stigma. We administered an online survey to 603 undergraduates (72 % female, 60 % White). SA was not significantly associated with BMI, but it was positively associated with weight stigma and exercise-avoidance motivation and negatively associated with self-reported exercise. SA moderated the relationship between BMI and exercise-avoidance motivation; individuals with higher BMIs were motivated to avoid exercise, but only if they reported higher SA. This interaction predicted exercise-avoidance motivation after accounting for weight stigma and its interaction with BMI. However, SA did not moderate the relationship between BMI and self-reported exercise. SA may be associated with exercise avoidance among higher weight individuals.


Assuntos
Ansiedade/psicologia , Aprendizagem da Esquiva , Índice de Massa Corporal , Exercício Físico/psicologia , Motivação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Preconceito de Peso/psicologia , Adulto Jovem
11.
Clin Psychol Rev ; 78: 101851, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32224363

RESUMO

Exposure therapy is a potential method for the treatment of eating disorders. The current paper reviews the literature on exposure interventions for eating disorders, including studies (N = 60) on exposure and response prevention (ERP), in vivo feared food exposure, mirror exposure, family-based treatment with exposure, and virtual reality exposure therapy. Mirror exposure alone or in the context of cognitive-behavioral therapy (CBT) can decrease body dissatisfaction. The few controlled trials on ERP for binge and purge cues show only marginal benefit of ERP for binge or purge cues over and above other treatment methods such as CBT. In vivo exposure to feared foods may decrease state anxiety and increase caloric intake and body mass index, but research is limited. Virtual reality exposure could improve accessibility and feasibility of exposures in the clinical setting. A significant portion of the trials incorporated exposures into an overarching treatment such as CBT, body image therapy, or inpatient treatment, so the effects of exposure itself are difficult to parse apart. We discuss the state of the current literature in the context of learning theory and offer insights into new approaches to the application of exposure therapy in an eating disordered population.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Terapia Implosiva , Avaliação de Processos e Resultados em Cuidados de Saúde , Terapia de Exposição à Realidade Virtual , Humanos , Terapia Implosiva/métodos , Terapia de Exposição à Realidade Virtual/métodos
12.
Proc Natl Acad Sci U S A ; 117(8): 4152-4157, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32029596

RESUMO

Whenever a genetically homogenous population of bacterial cells is exposed to antibiotics, a tiny fraction of cells survives the treatment, the phenomenon known as bacterial persistence [G.L. Hobby et al., Exp. Biol. Med. 50, 281-285 (1942); J. Bigger, The Lancet 244, 497-500 (1944)]. Despite its biomedical relevance, the origin of the phenomenon is still unknown, and as a rare, phenotypically resistant subpopulation, persisters are notoriously hard to study and define. Using computerized tracking we show that persisters are small at birth and slowly replicating. We also determine that the high-persister mutant strain of Escherichia coli, HipQ, is associated with the phenotype of reduced phenotypic inheritance (RPI). We identify the gene responsible for RPI, ydcI, which encodes a transcription factor, and propose a mechanism whereby loss of phenotypic inheritance causes increased frequency of persisters. These results provide insight into the generation and maintenance of phenotypic variation and provide potential targets for the development of therapeutic strategies that tackle persistence in bacterial infections.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Ampicilina/farmacologia , Antibacterianos/farmacologia , Proteínas de Ligação a DNA/genética , Escherichia coli/genética , Escherichia coli/fisiologia , Proteínas de Escherichia coli/genética , Microfluídica , Modelos Biológicos , Mutação , Fatores de Transcrição/genética
13.
Lancet Oncol ; 21(3): 345-357, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32035020

RESUMO

BACKGROUND: Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms of the serine/threonine kinase AKT. The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, postmenopausal women aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-2 and oestrogen receptor-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer who had relapsed or progressed on an aromatase inhibitor were recruited from 19 hospitals in the UK. Enrolled participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off (starting on cycle 1 day 15) until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment allocation was done using an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival with a one-sided alpha of 0·20. Analyses were done by intention to treat. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, number NCT01992952. FINDINGS: Between March 16, 2015, and March 6, 2018, 183 patients were screened for eligibility, of whom 140 (76%) were eligible and were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up for progression-free survival was 4·9 months (IQR 1·6-11·6). At the time of primary analysis for progression-free survival (Jan 30, 2019), 112 progression-free survival events had occurred, 49 (71%) in 69 patients in the capivasertib group compared with 63 (89%) of 71 in the placebo group. Median progression-free survival was 10·3 months (95% CI 5·0-13·2) in the capivasertib group versus 4·8 months (3·1-7·7) in the placebo group, giving an unadjusted hazard ratio (HR) of 0·58 (95% CI 0·39-0·84) in favour of the capivasertib group (two-sided p=0·0044; one-sided log rank test p=0·0018). The most common grade 3-4 adverse events were hypertension (22 [32%] of 69 patients in the capivasertib group vs 17 [24%] of 71 in the placebo group), diarrhoea (ten [14%] vs three [4%]), rash (14 [20%] vs 0), infection (four [6%] vs two [3%]), and fatigue (one [1%] vs three [4%]). Serious adverse reactions occurred only in the capivasertib group, and were acute kidney injury (two), diarrhoea (three), rash (two), hyperglycaemia (one), loss of consciousness (one), sepsis (one), and vomiting (one). One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment. One further death in the capivasertib group had an unknown cause; all remaining deaths in both groups (19 in the capivasertib group and 31 in the placebo group) were disease related. INTERPRETATION: Progression-free survival was significantly longer in participants who received capivasertib than in those who received placebo. The combination of capivasertib and fulvestrant warrants further investigation in phase 3 trials. FUNDING: AstraZeneca and Cancer Research UK.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Método Duplo-Cego , Feminino , Seguimentos , Fulvestranto/administração & dosagem , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Terapia de Salvação , Taxa de Sobrevida
14.
J Crit Care ; 56: 132-139, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31896447

RESUMO

INTRODUCTION: Although family members of incapacitated, critically ill patients often struggle in the role of surrogate decision maker, there are no low-cost, easily-scaled interventions to address this problem. AIM OF THE STUDY: To develop and pilot-test the Family Support Tool, an interactive, web-based tool to help individuals navigate the complexities of surrogate decision making in ICUs. MATERIAL AND METHODS: We used a mixed methods, user-centered process to create the Family Support Tool, including: 1) creation of a preliminary design by an expert panel; 2) engagement of a key stakeholder panel to iteratively refine the preliminary design; 3) user testing of a low-fidelity prototype of the tool by 6 former ICU surrogates; 4) creation of a web-based prototype; and 5) user testing of the web-based prototype with 14 surrogates and ICU physicians, including semi-structured interviews and quantitative measurement of usability, acceptability, and perceived effectiveness. RESULTS: The initial design contained a collection of videos and exercises designed to help individuals understand the surrogate's role and think through the patient's values and preferences. Based on family stakeholders' feedback about the emotional overwhelm they experience early in an ICU stay, we redesigned the tool to be viewed in sections, with the first section focused on decreasing surrogates' emotional distress, and later sections focused on helping surrogates prepare for family meetings. Surrogates actively making decisions in the ICU judged the final tool to be highly usable (mean summary score 83.5, correlating to 95th percentile when normalized to devices of its type), acceptable (mean 4.2 +/- 0.5 out of 5), and effective (mean 4.3 +/- 0.6 out of 5). All surrogates reported the tool helped them consider goals of care and all indicated they would recommend the tool to a friend. CONCLUSIONS: We successfully developed a web-based tool to help individuals navigate the complexities of surrogate decision making in ICUs that has high potential for scalability. Surrogates judged the tool to be usable, acceptable, and effective. These data support proceeding to test the tool in a pilot randomized clinical trial.


Assuntos
Estado Terminal/terapia , Tomada de Decisões , Família , Unidades de Terapia Intensiva , Relações Profissional-Família , Consentimento do Representante Legal , Adulto , Idoso , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Desenvolvimento de Programas
15.
ISME J ; 14(4): 919-930, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31896783

RESUMO

Mycobacterium bovis is the causative agent of bovine tuberculosis and the predominant cause of zoonotic tuberculosis in people. Bovine tuberculosis occurs in farmed cattle but also in a variety of wild animals, which form a reservoir of infection. Although direct transmission of tuberculosis occurs between mammals, the low frequency of contact between different host species and abundant shedding of bacilli by infected animals suggests an infectious route via environmental contamination. Other intracellular pathogens that transmit via the environment deploy strategies to survive or exploit predation by environmental amoebae. To explore if M. bovis has this capability, we investigated its interactions with the soil and dung-dwelling amoeba, Dictyostelium discoideum. We demonstrated that M. bovis evades phagocytosis and destruction by D. discoideum and actively transits through the amoeba using the ESX-1 Type VII Secretion System as part of a programme of mechanisms, many of which have been co-opted as virulence factors in the mammalian host. This capacity of M. bovis to utilise an environmental stage between mammalian hosts may enhance its transmissibility. In addition, our data provide molecular evidence to support an evolutionary role for amoebae as training grounds for the pathogenic M. tuberculosis complex.


Assuntos
Dictyostelium/fisiologia , Mycobacterium bovis/fisiologia , Amoeba , Animais , Animais Selvagens , Bovinos , Fezes , Solo , Microbiologia do Solo , Tuberculose Bovina/microbiologia , Sistemas de Secreção Tipo I , Sistemas de Secreção Tipo VII , Fatores de Virulência
16.
Front Immunol ; 11: 616188, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33597950

RESUMO

Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.


Assuntos
Envelhecimento , Biomarcadores Tumorais , Neoplasias da Mama , Estilo de Vida , Feminino , Perfilação da Expressão Gênica , Humanos , Fenômica , Fatores de Risco , Transcriptoma
17.
Health Info Libr J ; 36(3): 278-282, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31541531

RESUMO

This paper is based on Rachel Butler's dissertation carried out at the University of Sheffield as part of the MA Library and Information Services Management. The study examines people's online health information seeking skills, with the specific aim to identify how libraries and health services can work together in supporting digital and health literacy. A survey approach is used to explore online searching habits as well as librarian and health professionals' views on health literacy. The key findings indicate that whilst the majority of respondents consider themselves to be health literate, there was an overall agreement that effective education and support could be achieved through the collaboration between libraries and health services, and specifically to signpost information and to provide targeted education. The limitations of the research for dissertation are recognised leading to recommendations that further study focuses on the impact of signposting and education on health literacy.F.J.


Assuntos
Comportamento de Busca de Informação , Bibliotecários/psicologia , Papel Profissional/psicologia , Letramento em Saúde/normas , Humanos , Entrevistas como Assunto/métodos , Bibliotecários/estatística & dados numéricos , Pesquisa Qualitativa , Inquéritos e Questionários , Reino Unido
18.
Behav Res Ther ; 121: 103453, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31430688

RESUMO

OBJECTIVE: Sudden gains (SGs) have been found to occur during randomized controlled trials (RCTs) for social anxiety disorder (SAD). Evidence is mixed whether SGs relate to treatment outcome in SAD. We examined SGs in two RCTs for SAD. METHOD: Study 1 (N = 68) examined SGs in individual cognitive-behavioral therapy (CBT), and Study 2 (N = 100) compared SGs in group CBT and Mindfulness-Based Stress Reduction (MBSR). Weekly ratings of social anxiety were used to calculate SGs. The Liebowitz Social Anxiety Scale-Self-Report and the Social Interaction Anxiety Scale were completed at pretreatment, posttreatment, and follow-up to assess outcome. RESULTS: In Study 1, 17.6% of participants experienced a SG. Participants with SGs started and ended treatment with lower social anxiety. SGs were not associated with greater decreases in social anxiety from pre-to posttreatment or 12-month follow-up. In Study 2, SGs occurred in 27% of participants and at comparable rates in MBSR and group CBT. SGs were not associated with changes in social anxiety during treatment in either condition. CONCLUSION: SGs occurred during treatment for SAD. In both RCTs, participants improved regardless of experiencing a SG, suggesting that SGs are not predictive of greater improvement during treatment for SAD.


Assuntos
Terapia Cognitivo-Comportamental , Atenção Plena , Fobia Social/terapia , Adulto , Feminino , Humanos , Masculino , Fobia Social/psicologia , Psicoterapia de Grupo , Resultado do Tratamento , Adulto Jovem
19.
J Anxiety Disord ; 66: 102116, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31357038

RESUMO

Transgender and gender nonconforming (TGNC) individuals frequently confront discrimination, rejection, and violence. Such experiences may put TGNC individuals at risk for minority stress and associated psychiatric symptoms. Protective factors like social support, pride in one's gender identity, or connectedness to similar others may make TGNC individuals less vulnerable to psychiatric symptoms, and the presence of risk and protective factors may vary depending on living environment. This study examined the relationship of living environment (urban vs. suburban vs. small-town/rural) to social anxiety (SA) in a sample of 902 TGNC individuals who participated in the Trans Health Survey. Analysis of variance revealed a significant difference in SA across living environments. Those living in small-town/rural environments reported significantly higher levels of SA compared to those living in urban environments. There was a trend-level difference in SA in suburban compared to urban environments. Linear regression analyses revealed that living environment significantly moderated the relationship between social support and SA. Higher social support was more protective against elevated SA in urban and suburban than in small-town/rural environments. This study is the first to demonstrate the experience of elevated SA among TGNC individuals living in rural environments. Implications and future directions for research are discussed.


Assuntos
Fobia Social/epidemiologia , Fobia Social/psicologia , População Rural/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Canadá/epidemiologia , Feminino , Humanos , Masculino , Apoio Social , Estados Unidos/epidemiologia
20.
Prenat Diagn ; 39(10): 866-870, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31169930

RESUMO

OBJECTIVE: Outcomes from in vitro fertilization (IVF)/intrauterine insemination (ICSI) cycles for patients who underwent preimplantation genetic testing for monogenic/single gene (PGT-M) and structural chromosome rearrangements (PGT-SR) patients were reviewed. Patients pursuing PGT-M and PGT-SR often do not have pre-existing fertility issues and therefore may have uncertain expectations of successful outcomes. Before pursuing PGT-M and PGT-SR, patients require evidence-based counseling regarding the probability of having a healthy child. METHOD: Retrospective review from a single private IVF clinic of 73 PGT patients, from whom a total of 437 blastocysts were biopsied and screened. Embryo results and pregnancy outcomes were analyzed. RESULTS: Of the 45 PGT-M patients, 64.4% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 89.7%, with an ongoing pregnancy or delivery rate of 48.9%. For the 28 PGT-SR patients, 60.7% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 87.5%, with an ongoing pregnancy or delivery rate of 42.9%. CONCLUSION: This information can supplement the existing data in the literature to counsel new patients in terms of realistic expectations of success following PGT-M and PGT-SR.


Assuntos
Aberrações Cromossômicas , Doenças Genéticas Inatas/diagnóstico , Testes Genéticos/métodos , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Implantação/métodos , Adulto , Biópsia , Blastocisto/patologia , Canadá/epidemiologia , Aberrações Cromossômicas/estatística & dados numéricos , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Feminino , Clínicas de Fertilização , Fertilização In Vitro/métodos , Fertilização In Vitro/estatística & dados numéricos , Doenças Genéticas Inatas/epidemiologia , Testes Genéticos/estatística & dados numéricos , Humanos , Padrões de Herança , Masculino , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos
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