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The purpose of this study was to evaluate a local natural healing service program and to explore how engagement in natural healing services related to the well-being of survivors of domestic violence. Using longitudinal secondary data, we conducted t-tests, regression, and correlation analysis on three measures (hope, distress, and empowerment) that were completed by the participants (N = 31). We provided evidence of the positive impact of a community-based natural healing services program on the well-being of survivors of domestic violence, specifically their sense of hope. This research represents the potential for natural healing services provided at the community level.
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BACKGROUND: Fluorine-18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) is the standard for detecting myocardial inflammation in cardiac sarcoidosis, requiring preparation with the ketogenic diet (KD) to achieve myocardial glucose suppression. Despite this, incomplete myocardial glucose suppression remains a significant issue, and strategies to reduce myocardial glucose uptake (MGU) and identify incomplete myocardial glucose suppression are required. This study sought to understand the relationship between point-of-care beta-hydroxybutyrate (BHB) and different patterns of MGU and between KD and fasting duration with MGU in patients undergoing evaluation for cardiac sarcoidosis. METHODS: We prospectively included 471 outpatients who underwent FDG-PET for cardiac sarcoidosis evaluation, followed the KD for 1 (n=100), 2 (n=29), and ≥3 days (n=342), fasted for at least 12 hours, and had BHB levels measured immediately before FDG injection. Images were classified as (1) no MGU (negative), (2) focal/multifocal (positive), (3) diffuse (nondiagnostic), or (4) nonspecific uptake (NS-MGU). RESULTS: Cardiac FDG-PET scans were interpreted as the following: 376 (79.83%) negative; 61 (12.95%) positive; 14 (2.97%) diffuse; and 20 (4.25%) NS-MGU. There was a strong negative relationship between BHB levels and MGU (P<0.0001). BHB levels increased significantly with KD duration (P<0.0001) and fasting time (P=0.0067). The combined rate of diffuse, NS-MGU, and positive scans (34%, 28%, 16%) decreased inversely with KD duration (1, 2, and ≥3 days, respectively). However, MGU was not different across different fasting times (P=0.6). Blood glucose levels were not associated with MGU (P=0.17) and only weakly associated with BHB levels (R2=0.03; P<0.001). CONCLUSIONS: We observed a strong inverse relationship between ketosis and patterns of MGU. Longer KD and fasting durations are associated with higher ketosis. However, only KD duration was associated with lower rates of MGU. Measurement of BHB levels before FDG-PET using point-of-care testing is feasible and may facilitate the management of patients referred for myocardial inflammation.
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Violent behaviour perpetrated against women has long-lasting negative physical and mental health consequences for women, their children, their families, and their communities. Intimate partner violence (IPV) is associated with many adverse physical, psychological, and emotional consequences. Structural racism and historical trauma affect women's trust and further hinder the ability of Indigenous and Black women to seek help after experiencing IPV. The availability of IPV support services, which can include shelter, food, group therapy, legal assistance, and advocacy, can be inaccessible to women due to the inability to access often limited resources in urban environments and reasons compounded by potential geographic distance if living in rural areas or living in community. Understanding the unique reasons why Indigenous and Black women do not seek help, and the barriers they experience when seeking help after IPV, is critical. Pandemics have the potential to create further complexities on how IPV is experienced. Black and Indigenous women experiencing IPV were therefore at even greater risk for IPV-related harm because of state and local "stay at home" measures put in place to minimise the spread COVID-19. The purpose of this manuscript is to explicate the methods for a large R01 study in the Upper Midwest.
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Negro ou Afro-Americano , Indígenas Norte-Americanos , Violência por Parceiro Íntimo , Adulto , Feminino , Humanos , Negro ou Afro-Americano/psicologia , Comportamento de Busca de Ajuda , Violência por Parceiro Íntimo/psicologia , Violência por Parceiro Íntimo/etnologia , Meio-Oeste dos Estados Unidos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Indígenas Norte-Americanos/psicologiaRESUMO
PURPOSE: Immunologic response to anti-programmed cell death protein 1 (PD-1) therapy can occur rapidly with T-cell responses detectable in as little as one week. Given that activated immune cells are FDG avid, we hypothesized that an early FDG PET/CT obtained approximately 1 week after starting pembrolizumab could be used to visualize a metabolic flare (MF), with increased tumor FDG activity due to infiltration by activated immune cells, or a metabolic response (MR), due to tumor cell death, that would predict response. PATIENTS AND METHODS: Nineteen patients with advanced melanoma scheduled to receive pembrolizumab were prospectively enrolled. FDG PET/CT imaging was performed at baseline and approximately 1 week after starting treatment. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax) and thresholds were identified by ROC analysis; MF was defined as >70% increase in tumor SUVmax, and MR as >30% decrease in tumor SUVmax. RESULTS: An MF or MR was identified in 6 of 11 (55%) responders and 0 of 8 (0%) nonresponders, with an objective response rate (ORR) of 100% in the MF-MR group and an ORR of 38% in the stable metabolism (SM) group. An MF or MR was associated with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor. Overall survival at 3 years was 83% in the MF-MR group and 62% in the SM group. Median progression-free survival (PFS) was >38 months (median not reached) in the MF-MR group and 2.8 months (95% confidence interval, 0.3-5.2) in the SM group (P = 0.017). CONCLUSIONS: Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with PFS.
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Anticorpos Monoclonais Humanizados , Fluordesoxiglucose F18 , Melanoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/diagnóstico por imagem , Melanoma/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Fluordesoxiglucose F18/administração & dosagem , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Estudos Prospectivos , Prognóstico , Idoso de 80 Anos ou mais , Compostos RadiofarmacêuticosRESUMO
Intimate partner violence (IPV) is a complex and pervasive public health problem disproportionately affecting Indigenous and Black women. During the COVID-19 pandemic, IPV became more complicated for advocates because social distancing, quarantine, and isolation measures further endangered women experiencing IPV. This manuscript is based on an ongoing community-engaged study in an upper Midwestern state. Our primary goal for this study is to generate urgently needed knowledge on the impact of the COVID-19 pandemic on Indigenous and Black women's help-seeking behaviours following IPV by systematically documenting barriers women faced during the pandemic. Engaging women in a large study that seeks to garner information about their experiences of violence is complex and challenging and requires significant planning, especially for ensuring participants' safety. In this write-up, we detail the safety planning protocol developed for the purposes of recruiting and engaging women in rural and urban areas in an upper Midwestern state in the United States. Our goal is to provide scholars conducting research in the area of violence with practical considerations for safely conducting a study of this nature.
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COVID-19 , Violência por Parceiro Íntimo , Humanos , Feminino , Estados Unidos , PandemiasRESUMO
Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, and, like cigarette use, can cause pulmonary inflammation and increase the risk of lung disease. Methods: This preliminary study used PET with 18F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine (18F-NOS) to quantify inducible nitric oxide synthase expression to characterize oxidative stress and inflammation in the lungs in vivo in 3 age- and sex-matched groups: 5 EC users, 5 cigarette smokers, and 5 controls who had never smoked or vaped. Results: EC users showed greater 18F-NOS nondisplaceable binding potential (BPND) than cigarette smokers (P = 0.03) and controls (P = 0.01), whereas BPND in cigarette smokers did not differ from that in controls (P > 0.1). 18F-NOS lung tissue delivery and inducible nitric oxide synthase distribution volume did not significantly differ among groups. Although there were no group differences in peripheral inflammatory biomarker concentrations, 18F-NOS BPND correlated with the proinflammatory cytokine tumor necrosis factor-α concentrations (rs = 0.87, P = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, number of vaping episodes or cigarettes per day correlated with interleukin-6 levels (rs = 0.86, P = 0.006). Conclusion: This is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo. We found preliminary evidence that EC users have greater pulmonary inflammation than cigarette smokers and controls, with a positive association between pulmonary and peripheral measures of inflammation.
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Sistemas Eletrônicos de Liberação de Nicotina , Pneumonia , Produtos do Tabaco , Adulto Jovem , Humanos , Adolescente , Projetos Piloto , Óxido Nítrico Sintase Tipo II , Produtos do Tabaco/efeitos adversos , Inflamação/diagnóstico por imagem , Eletrônica , Imagem MolecularRESUMO
Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUVmax (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUVmax cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUVmax cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.
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Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Ácidos Carboxílicos , Tomografia por Emissão de Pósitrons , AminoácidosRESUMO
AIMS: To develop an innovative community-academic partnership to advance, test and promote intimate partner violence screening and referral protocols by comparing the effect of integrating intimate partner violence advocates versus enhancing medical training in medical clinic settings serving women from vulnerable populations. Detecting intimate partner violence in healthcare settings allows for survivors to connect to safety and referral resources prior to violence escalating. Screening for intimate partner violence and connecting patients to referral resources requires creating a safe and trusting relationship between healthcare providers and patients. Developing screening and referral protocols responsive to survivors' needs requires involvement of clinic staff, survivors and community agencies that support survivors. DESIGN: Three phases of the project include Discovery, Implementation and Dissemination. Mixed-methodology will help in understanding current practices and effects of interventions. METHODS: Actions included in each phase: Discovery: 1) nurse-led focus groups of clinic staff, providers and survivors to understand current clinic practices; 2) retrospective chart review of the number of screens performed, positive screens detected and interventions performed. IMPLEMENTATION: 1) randomization of patients to be interviewed by a trained advocate or by healthcare provider with enhanced training; and 2) assess the number of screenings and referrals performed in each arm and 3) evaluate outcomes of intervention. Dissemination through: presentations, manuscripts and policy recommendations at the institutional and regional level. This IRB-approved proposal was funded in July 2021 by an Advancing a Healthier Wisconsin grant. DISCUSSION: The partnership has improved channels of communication and understanding between diverse clinical care providers, survivors and community agency staff as they navigate the complex challenges to the development and integration of screening and referral protocols. IMPACT: This project will provide evidence of the most effective intimate partner violence screening and referral methodology that can be utilized in a wide variety of medical settings.
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Violência por Parceiro Íntimo , Humanos , Feminino , Estudos Retrospectivos , Violência por Parceiro Íntimo/prevenção & controle , Instituições de Assistência Ambulatorial , Nível de Saúde , Atenção à SaúdeRESUMO
BACKGROUND: Somatostatin receptor is expressed in sarcoid granulomas, and preliminary clinical studies have shown that myocardial sarcoidosis can be identified on somatostatin receptor-targeted PET. We examined the potential clinical use of 68Ga-DOTATATE PET/CT for diagnosis and response assessment in cardiac sarcoidosis compared to 18F-FDG PET/CT. METHODS: Eleven cardiac sarcoidosis patients with 18F-FDG PET/CT were prospectively enrolled for cardiac 68Ga-DOTATATE PET/CT. The two PET/CT studies were interpreted independently and were compared for patient-level and segment-level concordance, as well as for the degree of radiotracer uptake. Follow-up 68Ga-DOTATATE PET/CT was performed in eight patients. RESULTS: Patient-level concordance was 91%: ten patients had multifocal DOTATATE uptake (active cardiac sarcoidosis) and one patient showed diffuse DOTATATE uptake. Segment-level agreement was 77.1% (Kappa 0.53 ± 0.07). The SUVmax-to-blood pool ratio was lower on 68Ga-DOTATATE PET/CT (3.2 ± 0.6 vs. 4.9 ± 1.5, P = 0.006 on paired t test). Follow-up 68Ga-DOTATATE PET/CT showed one case of complete response and one case of partial response, while 18F-FDG PET/CT showed four cases of response, including three with complete response. CONCLUSION: Compared to 18F-FDG PET/CT, 68Ga-DOTATATE PET/CT can identify active cardiac sarcoidosis with high patient-level concordance, but with moderate segment-level concordance, low signal-to-background ratio, and underestimation of treatment response.
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Compostos Organometálicos , Sarcoidose , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Receptores de SomatostatinaRESUMO
Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has shown promise for use in assessing treatment response in patients with bone-only or bone-dominant (BD) metastatic breast cancer (mBC). In this single-institution, prospective single-arm study of 23 women (median age, 59 years [range, 38-81 years]) with biopsy-proven estrogen receptor-positive bone-only or BD mBC about to begin new endocrine therapy between October 3, 2013, and August 3, 2018, the value of early 4-week 18F-FDG PET/CT in predicting progression-free survival (PFS) was evaluated. 18F-FDG PET/CT was performed at baseline, 4 weeks, and 12 weeks. Maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) were measured for up to five index lesions. The primary end point was PFS. Secondary end points were overall survival (OS) and time to skeletal-related events (tSREs). All end points were compared between responders (reduction of 30% or more in the sum of SUVmax for target lesions) and nonresponders at 4 weeks and 12 weeks. Percentage change from baseline in SUVmax at 4- and 12-week 18F-FDG PET/CT were highly correlated (r = 0.81). At the 4-week time point PET responders had numerically longer PFS (14.2 months vs 6.3 months; P = .53), OS (44.0 months vs 29.7 months; P = .47), and tSRE (27.4 months vs 25.2 months; P = .66) compared with nonresponders, suggesting the clinical utility of 4-week 18F-FDG PET/CT as an early predictor of treatment failure. Keywords: Breast Cancer, Metastatic Breast Cancer, Bone-Dominant Metastatic Breast Cancer, FDG PET/CT, Estrogen-Receptor Positive Metastatic Breast Cancer Supplemental material is available for this article. Clinical trial registration no. NCT04316117 © RSNA, 2022.
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Neoplasias Ósseas , Neoplasias da Mama , Feminino , Humanos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia , Neoplasias Ósseas/secundário , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Estrogênios/uso terapêutico , Flúor/uso terapêutico , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Receptores de Estrogênio/uso terapêutico , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising molecular target for imaging of prostate adenocarcinoma. 68Ga-P16-093, a small molecule PSMA ligand, previously showed equivalent diagnostic performance compared to 68Ga-PSMA-11 PET/CT in a pilot study of prostate cancer patients with biochemical recurrence (BCR). We performed a pilot study for further characterization of 68Ga-P16-093 including comparison to conventional imaging. PROCEDURES: Patients were enrolled into two cohorts. The biodistribution cohort included 8 treated prostate cancer patients without recurrence, who underwent 6 whole body PET/CT scans with urine sampling for dosimetry using OLINDA/EXM. The dynamic cohort included 15 patients with BCR and 2 patients with primary prostate cancer. Two patients with renal cell carcinoma were also enrolled for exploratory use. A dynamic PET/CT was followed by 2 whole body scans for imaging protocol optimization based on bootstrapped replicates. 68Ga-P16-093 PET/CT was compared for diagnostic performance against available 18F-fluciclovine PET/CT, 99mTc-MDP scintigraphy, diagnostic CT, and MRI. RESULTS: 68Ga-P16-093 deposited similar effective dose (0.024 mSv/MBq) and lower urinary bladder dose (0.064 mSv/MBq) compared to 68Ga-PSMA-11. The kidneys were the critical organ (0.290 mSv/MBq). While higher injected activities were preferable, lower injected activities at 74-111 MBq (2-3 mCi) yielded 80% retention in signal-to-noise ratio. The optimal injection-to-scan interval was 60 min, with acceptable delay up to 90 min. 68Ga-P16-093 PET/CT showed superior diagnostic performance over conventional imaging with overall patient-level lesion detection rate of 71%, leading to a change in management in 42% of the patients. CONCLUSIONS: Based on its favorable imaging characteristics and diagnostic performance in prostate cancer, 68Ga-P16-093 PET/CT merits further investigation in larger clinical studies.
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Radioisótopos de Gálio , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Próstata/patologia , Distribuição Tecidual , Ligantes , Projetos Piloto , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Ácido EdéticoRESUMO
Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022.
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Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Feminino , Humanos , Estudos Multicêntricos como Assunto , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Estados UnidosRESUMO
The ketogenic diet (KD) is the standard of care to achieve myocardial glucose suppression (MGS) for assessing inflammation using 18F-FDG PET. However, failure to suppress physiologic glucose uptake remains a significant diagnostic barrier. Although extending the duration of KD may be effective, exogenously delivered ketones may provide a convenient, reliable, and same-day alternative. The aims of our study were to determine whether exogenous ketone administration is noninferior to the KD to achieve MGS and whether serum ß-hydroxybutyrate (BHB) levels can predict MGS. Methods: KEETO-CROSS (Ketogenic Endogenous versus Exogenous Therapies for myoCaRdial glucOse SuppresSion) is a crossover, noninferiority trial of the KD (endogenous ketosis) versus ketone ester ([KE] exogenous ketosis) drink. Twenty healthy participants were enrolled into 3 arms: weight-based KE drink, 24-h KD, and 72-h KD (n = 18 completed all arms). The primary outcome was achievement of complete MGS on PET (noninferiority margin 5%). The area under receiver-operating-characteristics (AUROC) of endogenous BHB levels (analyzed in a laboratory and by point-of-care device) for predicting MGS was analyzed in 37 scans completed on the KD. Results: The mean age was 30 ± 7 y, 50% were women, and 45% were nonwhite. The median achieved BHB levels (mmol/L) were 3.82 (25th-75th percentile, 2.55-4.97) (KE drink), 0.77 (25th-75th percentile, 0.58-1.02) (25th-75th percentile, 24-h KD), and 1.30 (25th-75th percentile, 0.80-2.24) (72-h KD). The primary outcome was achieved in 44% (KE drink), 78% (24-h KD), and 83% (72-h KD) of participants (noninferiority P = 0.97 and 0.98 for KE vs. 24-h and 72-h KD). Endogenous BHB levels robustly predicted MGS (AUROC, 0.88; 95% CI 0.71, 1.00). A BHB of 0.58 or more correctly classified 92% of scans. A point-of-care device provided comparable predictive value. Conclusion: In healthy volunteers, KE was inferior to KD for achieving MGS. Serum BHB is a highly predictive biomarker for MGS and can be clinically implemented upstream of 18F-FDG PET, with rapid facilitation by point-of-care testing, to reduce false-positive scans.
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Cetonas , Cetose , Ácido 3-Hidroxibutírico , Adulto , Estudos Cross-Over , Carboidratos da Dieta , Feminino , Fluordesoxiglucose F18 , Glucose , Humanos , Masculino , Adulto JovemRESUMO
Impacting 1 in 4 children in the United States, childhood exposure to domestic violence predicts myriad negative sequelae. Intervening post exposure is critical to help children and their protective parent heal and avoid long-term negative consequences. Children aged 2-17 and their mothers who were victims of domestic violence participated in a 12-week group program delivered by domestic violence agency staff that provides psychoeducation on the impact of trauma and domestic violence and aims to improve parent and child well-being. The impact of the Child Witness to Domestic Violence (CWDV) program was tested in an intervention group (n = 69 children, 33 mothers) who participated in CWDV and control group (n = 80 children, 39 mothers) consisting of children whose mothers received adult-focused domestic violence services but were not enrolled in CWDV or other child-focused services. Multiple regression analyses controlling for child gender, child age, mother's age, and the outcome of interest at time 1 found that participation in CWDV program significantly predicted better child functioning as indicated by less hyperactivity (B = -.85, p = .06), fewer negative emotional symptoms (B = -1.14, p = .01), and fewer total behavioral difficulties (B = -2.48, p = .02) as well as higher maternal hope (B = .57, p = .03). These data provide promising evidence of the impact of a brief, replicable group intervention that promotes healing and well-being among children and parents exposed to domestic violence. Limitations include a quasi-experimental design and reliance on maternal report.
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Violência Doméstica , Violência por Parceiro Íntimo , Adulto , Criança , Intervenção em Crise , Violência Doméstica/psicologia , Emoções , Feminino , Humanos , Mães/psicologia , PaisRESUMO
The poly-(adenosine diphosphate-ribose) polymerase (PARP) family of proteins participates in numerous functions, most notably the DNA damage response. Cancer vulnerability to DNA damage has led to development of several PARP inhibitors (PARPi). This class of drugs has demonstrated therapeutic efficacy in ovarian, breast, and prostate cancers, but with variable response. Consequently, clinics need to select patients likely to benefit from these targeted therapies. In vivo imaging of 18F-fluorthanatrace uptake has been shown to correspond to PARP-1 expression in tissue. This study characterized the pharmacokinetics of 18F-fluorthanatrace and tested kinetic and static models to guide metric selection in future studies assessing 18F-fluorthanatrace as a biomarker of response to PARPi therapy. Methods: Fourteen prospectively enrolled ovarian cancer patients were injected with 18F-fluorthanatrace and imaged dynamically for 60 min after injection followed by up to 2 whole-body scans, with venous blood activity and metabolite measurements. SUVmax and SUVpeak were extracted from dynamic images and whole-body scans. Kinetic parameter estimates and SUVs were assessed for correlations with tissue PARP-1 immunofluorescence (n = 7). Simulations of population kinetic parameters enabled estimation of measurement bias and precision in parameter estimates. Results:18F-fluorthanatrace blood clearance was variable, but labeled metabolite profiles were similar across patients, supporting use of a population parent fraction curve. The total distribution volume from a reversible 2-tissue-compartment model and Logan reference tissue distribution volume ratio (DVR) from the first hour of PET acquisition correlated with tumor PARP-1 expression by immunofluorescence (r = 0.76 and 0.83, respectively; P < 0.05). DVR bias and precision estimates were 6.4% and 29.1%, respectively. SUVmax and SUVpeak acquired from images with midpoints of 57.5, 110 ± 3, and 199 ± 4 min highly correlated with PARP-1 expression (mean ± SD, r ≥ 0.79; P < 0.05). Conclusion: Tumor SUVmax and SUVpeak at 55-60 min after injection and later and DVR from at least 60 min appear to be robust noninvasive measures of PARP-1 binding. 18F-fluorthanatrace uptake in ovarian cancer was best described by models of reversible binding. However, pharmacokinetic patterns of tracer uptake were somewhat variable, especially at later time points.
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Tomografia por Emissão de PósitronsRESUMO
There is a growing interest in developing comprehensive assessments that measure intimate partner violence (IPV) alongside other adverse events that correlate with IPV and compound its effects. One promising line of research in this area has focused on the impact of exposure to multiple types of victimization, i.e., polyvictimization. The purpose of this study is to examine the experience of administration of a polyvictimization tool from staff and client perspectives in order to inform future tool developments and assessment procedures. Qualitative interviews and focus groups with clients and staff from a family justice center who had experience with the assessment tool were used to identify strengths and challenges of the assessment too and inform future tool development. Findings demonstrate that an assessment tool provides the space for clients to talk about trauma and facilitate empowerment, while providing the opportunity for psychoeducation and service referrals. Concerns about the assessment tool included adverse reactions without proper framing and language, as well as shifting the emphasis from screening for adversities toward strengths, coping skills, and resilience. Implications for future measurement development and establishing best practices in polyvictimization assessment are discussed, with an emphasis on the benefits of social service agencies utilizing assessment tools.
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Bullying , Vítimas de Crime , Violência por Parceiro Íntimo , Grupos Focais , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Justiça SocialRESUMO
Although children with incarcerated parents exhibit more behavior problems, health concerns, and academic difficulties than their peers, few interventions or resources are available to support affected children. This randomized, controlled, multisite efficacy trial evaluated Sesame Street's "Little Children, Big Challenges: Incarceration" initiative with children aged 3 to 8 years with a jailed father. Seventy-one diverse children and their caregivers were randomized to an educational outreach group (n = 32) or wait list control group (n = 39). Researchers observed children during jail visits and interviewed caregivers by phone 2 and 4 weeks later. The effects of the intervention on children's behavior and emotions occurring during a jail visit depended on what children had been told about the father's incarceration. Children who were told honest, developmentally appropriate explanations showed less negative affect at entry, an increase in negative affect when the intervention was administered, and a decrease in negative affect during the visit. Intervention group children who were told distortions, nothing, or explanations that were not developmentally appropriate showed more negative affect initially, and their negative affect remained relatively stable during their time in the jail. In addition, children who were told the simple, honest truth about the parent's incarceration (a recommendation in the educational materials) exhibited more positive affect during the visit, with a medium effect size. Caregivers in the educational outreach group reported more positive change in how they talked to children about the incarceration over time compared to the control group.
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Pais , Prisioneiros , Cuidadores , Criança , Pré-Escolar , Emoções , Pai , Humanos , MasculinoRESUMO
Histone deacetylase inhibitors (HDACIs) may overcome endocrine resistance in estrogen receptor-positive (ER+) metastatic breast cancer. We tested whether 18F-fluoroestradiol PET imaging would elucidate the pharmacodynamics of combination HDACIs and endocrine therapy. Methods: Patients with ER+/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer with prior clinical benefit from endocrine therapy but later progression on aromatase inhibitor (AI) therapy were given vorinostat (400 mg daily) sequentially or simultaneously with AI. 18F-fluoroestradiol PET and 18F-FDG PET scans were performed at baseline, week 2, and week 8. Results: Eight patients were treated sequentially, and then 15 simultaneously. Eight patients had stable disease at week 8, and 6 of these 8 patients had more than 6 mo of stable disease. Higher baseline 18F-fluoroestradiol uptake was associated with longer progression-free survival. 18F-fluoroestradiol uptake did not systematically increase with vorinostat exposure, indicating no change in regional ER estradiol binding, and 18F-FDG uptake did not show a significant decrease, as would have been expected with tumor regression. Conclusion: Simultaneous HDACIs and AI dosing in patients with cancer resistant to AI alone showed clinical benefit (6 or more months without progression) in 4 of 10 evaluable patients. Higher 18F-fluoroestradiol PET uptake identified patients likely to benefit from combination therapy, but vorinostat did not change ER expression at the level of detection of 18F-fluoroestradiol PET.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estradiol/análogos & derivados , Tomografia por Emissão de Pósitrons , Receptores de Estrogênio/metabolismo , Vorinostat/farmacologia , Adulto , Idoso , Neoplasias da Mama/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2/metabolismoRESUMO
INTRODUCTION: [68Ga]Ga-P15-041 ([68Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry. METHODS: Subjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic. Dosimetry was performed with 6 whole body PET acquisitions and urine collection spanning 3 h; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60 min acquisition over a site of known or suspected disease followed by two whole body scans. Bootstrapping and subsampling of the acquired list-mode data were conducted to recommend image acquisition parameters for future clinical trials. RESULTS: Up to 233 MBq (6.3 mCi) of [68Ga]Ga-P15-041 was injected into 12 enrolled volunteers, 8 in dosimetry and 4 in dynamic cohorts. Radiotracer accumulated in known bone lesions and cleared rapidly from blood and soft tissue. The highest individual organ dose was 0.135 mSv/MBq in the urinary bladder wall. The average effective dose was 0.0173 ± 0.0036 mSv/MBq. An average injected activity of 166.5 MBq (4.5 mCi) resulted in absorbed dose estimates of 22.5 mSv to the urinary bladder wall, 8.2 mSv to the kidneys, and an effective dose of 2.9 mSv. Lesion signal to noise ratios on images generated from subsampled data were significantly higher for injected activities above 74 MBq (2 mCi) and were also significantly higher for imaging at 90 min than at 180 min post-injection. CONCLUSIONS: Dosimetry estimates are acceptable and [68Ga]Ga-P15-041 uptake characteristics in patients with confirmed bone metastases support its continued development. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Use of [68Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.
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Ácido Edético/análogos & derivados , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Razão Sinal-Ruído , Adulto , Idoso , Transporte Biológico , Ácido Edético/efeitos adversos , Ácido Edético/metabolismo , Ácido Edético/farmacocinética , Humanos , Marcação por Isótopo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radiometria , Segurança , Distribuição TecidualRESUMO
The σ2 receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of 18F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether 18F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT02284919) between March 2015 and January 2017. Each received an injection of 278-527 MBq of 18F-ISO-1 and then underwent PET/CT imaging of the breasts 50-55 min later. In vivo uptake of 18F-ISO-1 was quantitated by SUVmax and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUVmax (median, 2.0 g/mL; range, 1.3-3.3 g/mL), partial-volume-corrected SUVmax, and SUV ratios were tested against Ki-67. Tumors stratified into the high-Ki-67 (≥20%) group had SUVmax greater than the low-Ki-67 (<20%) group (P = 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ = 0.46, P = 0.01, n = 29). Partial-volume-corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ = 0.51, P = 0.02, n = 21). Tumor-to-normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P > 0.05). Conclusion:18F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.