A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer.

BACKGROUND: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA-damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects. METHODS: A single-arm, open-label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients received temozolomide (150 mg/m2 /d) on days 1 to 5 and veliparib (40 mg twice daily) on days 1 to 7 of each 28-day cycle. Another 5 patients with mismatch repair-deficient (dMMR) tumors were also enrolled. Twenty additional patients were then treated with temozolomide at 200 mg/m2 /d. Archived tumor specimens were used for immunohistochemistry to assess mismatch repair, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression levels. RESULTS: The combination was well tolerated, although some patients required dose reductions for myelosuppression. The primary endpoint was successfully met with a DCR of 24% and 2 confirmed partial responses. The median progression-free survival was 1.8 months, and the median overall survival was 6.6 months. PTEN protein expression and MGMT protein expression were not predictors of DCR. There was also a suggestion of worse outcomes for patients with dMMR tumors. CONCLUSIONS: In this heavily pretreated mCRC population, a combination of veliparib and temozolomide was well tolerated with temozolomide doses up to 200 mg/m2 /d, and it was clinically active. PARP inhibitor-based therapy merits further exploration in patients with mCRC. Cancer 2018;124:2337-46. © 2018 American Cancer Society.

A Prognostic Indicator for Patients Hospitalized with Heart Failure.

BACKGROUND: Current methods for identifying patients at risk of dying within six months suffer from clinician biases resulting in underestimation of this risk. As a result, patients who are potentially eligible for hospice and palliative care services frequently do not benefit from these services until they are very close to the end of their lives. OBJECTIVE: To develop a prospective prognostic indicator based on actual survival within Centers for Medicare and Medicaid Services (CMS) claims data that identifies patients with congestive heart failure (CHF) who are at risk of six-month mortality. METHODS: CMS claims data from January 1, 2008 to June 30, 2009 were reviewed to find the first hospitalization for CHF patients with episode of care diagnosis-related groups (DRGs) 291, 292, and 293. Univariate and multivariable analyses were used to determine the associations between demographic and clinical factors and six-month mortality. The resulting model was evaluated for discrimination and calibration. RESULTS: The resulting prospective prognostic model demonstrated fair discrimination with an ROC of 0.71 and good calibration with a Hosmer-Lemshow statistic of 0.98. Across all DRGs, 5% of discharged patients had a six-month mortality risk of greater than 50%. CONCLUSION: This prospective approach appears to provide a method to identify patients with CHF who would potentially benefit from a clinical evaluation for referral to hospice care or for a palliative care consult due to high predicted risk of dying within 180 days after discharge from a hospital. This approach can provide a model to match at-risk patients with evidenced-based care in a more consistent manner. This method of identifying patients at risk needs further prospective evaluation to see if it has value for clinicians, increases referrals to hospice and palliative care services, and benefits patients and families.

Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma.

PURPOSE: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC). METHODS: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03. RESULTS: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months. CONCLUSION: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS. GOV IDENTIFIER: NCT01205828.

The psychological sequelae of violent injury in a pediatric intervention.

PURPOSE: Pediatric trauma centers have unique potential to prevent violent injury and its psychological sequelae. Hospital-based violence intervention programs (HVIPs) are proliferating across the U.S., but little is known about the psychological needs of pediatric patients who participate in them. The purpose of this study was to describe the prevalence of symptoms of posttraumatic stress and exposure to community violence among pediatric HVIP participants. METHODS: We conducted a cross-sectional analysis of psychosocial needs assessment data that were collected for 48 participants. The Child Trauma Screening Questionnaire (CTSQ) and modified Survey of Children's Exposure to Community Violence were used to assess primary outcomes. RESULTS: The sample was 62.5% male and had a mean age of 14.5 years. Twenty-three percent reported previously sustaining a violent injury resulting in medical care, and 47.8% had witnessed a shooting. The majority (66.0%) had a CTSQ score at/above the threshold for probable PTSD diagnosis. The mean CTSQ score was 5.9 and hyperarousal (3.3) symptoms were more common than re-experiencing symptoms (2.6). CONCLUSION: Pediatric HVIPs and trauma centers should consider integrating PTSD screening and trauma-focused psychoeducation into the practice and protocols. Future research should evaluate the impacts of these interventions.

Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement.

BACKGROUND: Health-care costs following acute hospital care have been identified as a major contributor to regional variation in Medicare spending. This study investigated the associations of preoperative physical therapy and post-acute care resource use and its effect on the total cost of care during primary hip or knee arthroplasty. METHODS: Historical claims data were analyzed using the Centers for Medicare & Medicaid Services Limited Data Set files for Diagnosis Related Group 470. Analysis included descriptive statistics of patient demographic characteristics, comorbidities, procedures, and post-acute care utilization patterns, which included skilled nursing facility, home health agency, or inpatient rehabilitation facility, during the ninety-day period after a surgical hospitalization. To evaluate the associations, we used bivariate and multivariate techniques focused on post-acute care use and total episode-of-care costs. RESULTS: The Limited Data Set provided 4733 index hip or knee replacement cases for analysis within the thirty-nine-county Medicare hospital referral cluster. Post-acute care utilization was a significant variable in the total cost of care for the ninety-day episode. Overall, 77.0% of patients used post-acute care services after surgery. Post-acute care utilization decreased if preoperative physical therapy was used, with only 54.2% of the preoperative physical therapy cohort using post-acute care services. However, 79.7% of the non-preoperative physical therapy cohort used post-acute care services. After adjusting for demographic characteristics and comorbidities, the use of preoperative physical therapy was associated with a significant 29% reduction in post-acute care use, including an $871 reduction of episode payment driven largely by a reduction in payments for skilled nursing facility ($1093), home health agency ($527), and inpatient rehabilitation ($172). CONCLUSIONS: The use of preoperative physical therapy was associated with a 29% decrease in the use of any post-acute care services. This association was sustained after adjusting for comorbidities, demographic characteristics, and procedural variables. CLINICAL RELEVANCE: Health-care providers can use this methodology to achieve an integrative, cost-effective, patient care pathway using preoperative physical therapy.

Terapia de aceitação e compromisso no tratamento da fobia de espaços fechados: ensaio clínico randomizado / Acceptance and Commitment Therapy to treat phobia of enclosed spaces: a randomized clinical trial

Os exames de Ressonância Magnética vêm sendo muito requisitados nas diferentes especialidades médicas como complemento diagnóstico e acompanhamento evolutivo de diversas patologias. Embora seja um método diagnóstico de excelência, os pacientes que se submetem ao exame podem apresentar muito desconforto em razão do espaço restrito do aparelho. A fobia de espaços fechados é considerada um tipo de fobia específica, segundo o Manual Diagnóstico e Estatístico de Transtornos Mentais DSM 5 (APA, 2013). OBJETIVOS: Verificar se uma sessão de Terapia de Aceitação e Compromisso é tão eficaz quanto sete sessões deste mesmo modelo terapêutico no tratamento de pacientes com medo de realizar exames de Ressonância Magnética. MÉTODO: Foi realizado um ensaio clínico randomizado com dois grupos paralelos, um grupo recebeu uma sessão e o outro grupo recebeu sete sessões de tratamento de Terapia de Aceitação e Compromisso. Os participantes foram avaliados no início e ao final do tratamento a partir dos seguintes instrumentos: Inventário de Claustrofobia de Rachman e Taylor (1993), Inventário de Depressão de Beck et al. (1961) e Inventário de Ansiedade estado-traço de Spielberger, Gorsuch e Lushene (1970). O estudo foi realizado em um hospital público na cidade de São Paulo com 30 pacientes. Desfecho principal: permanecer dentro de um simulador de Ressonância Magnética por, no mínimo, trinta minutos após o término de cada um dos tratamentos. Desfechos secundários: as diferenças nos escores dos Inventários de Claustrofobia, Inventário de Depressão de Beck e Inventário de Ansiedade Estado-traço do início e do final do tratamento. RESULTADOS: 92,9% dos participantes (N) do grupo de sete sessões conseguiram realizar exame de Ressonância Magnética no simulador após o tratamento, enquanto que 50% dos participantes do grupo de uma sessão conseguiram realizar o exame no simulador (p=0,033). Dos sujeitos que tiveram melhor resposta ao tratamento, 78% eram do sexo masculino, 80% eram...

The MRI exams have been in considerable demand in various medical specialties to diagnose diseases. Although it is an effective diagnostic method, patients who are subjected to the exam might present high levels of discomfort due to the confined space of the device. The phobia of enclosed spaces is considered a type of specific phobia, according to the Diagnostic and Statistical Manual of Mental Disorders 5 (APA, 2013). Objectives: to check if a single session of Acceptance and Commitment Therapy is as effective as seven sessions of the same therapeutic model for the treatment of patients with fear of undergoing MRI exams and enclosed spaces phobia. METHODS: A randomized clinical trial study with two parallel groups was performed, one group underwent one session and the other group underwent seven sessions of Acceptance and Commitment Therapy. Participants were assessed at the beginning and at the end of treatment with the following instruments: Claustrophobia Inventory from Rachman and Taylor (1993), Beck Depression Inventory from beck et al. (1961) and Anxiety Inventory State - Trait from Spielberger, Gorsuch and Luschene (1970). The study was performed in a public hospital in the city of Sao Paulo with 30 patients. Main outcome: to remain in a MRI simulator for at least 30 minutes after each treatment. Secondary outcomes: compare the differences in the inventories of Claustrophobia, Beck Depression Inventory and the Anxiety Inventory Trait- State scores compared at the beginning and at the end of treatments. RESULTS: 92.9% of participants (N) on the seven sessions group were able to carry out the MRI exam simulator after treatment, while 50% of participants of the one session group were able carry out the post treatment session in the simulator (p = 0.033). From the participants who had better response to treatment, 78 % were male, 80 % were married, 78 % did not use psychiatric medication and 20 % had a diagnosis of specific MRI phobia, 80% had a...