Abstract Plasmonic photothermal therapy (PPTT) is a minimally-invasive oncological treatment strategy in which photon energy is selectively administered and converted into heat sufficient to induce ...cellular hyperthermia. The present work demonstrates the feasibility of in vivo PPTT treatment of deep-tissue malignancies using easily-prepared plasmonic gold nanorods and a small, portable, inexpensive near-infrared (NIR) laser. Dramatic size decreases in squamous cell carcinoma xenografts were observed for direct ( P < 0.0001) and intravenous ( P < 0.0008) administration of pegylated gold nanorods in nu/nu mice. Inhibition of average tumor growth for both delivery methods was observed over a 13-day period, with resorption of >57% of the directly-injected tumors and 25% of the intravenously-treated tumors.
Magnetic cobalt spinel ferrite nanoparticles coated with biocompatible polygalacturonic acid were functionalized with ligands specific for targeting expressed EphA2 receptors on ovarian cancer cells. ...By using such magnetic nanoparticle−peptide conjugates, targeting and extraction of malignant cells were achieved with a magnetic field. Targeting ovarian cancer cells with receptor specific peptide-modified magnetic nanoparticles resulted in cell capture from a flow stream in vitro and from the peritoneal cavity of mice in vivo. Successful removal of metastatic cancer cells from the abdominal cavity and circulation using magnetic nanoparticle conjugates indicate the feasibility of a dialysis-like treatment and may improve long-term survival rates of ovarian cancer patients. This approach can be applied for fighting other cancers, such as leukemia, once the receptors on malignant cells are identified and the efficacy of targeting ligands is established.
Objective: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. ...Method: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication switch, or a medication switch plus CBT. This study examined five established symptom dimensions (Child Depression Rating Scale--Revised) at baseline as they predicted recovery over 24 weeks of acute and continuation treatment. The two indices of recovery that were evaluated were time to remission and number of depression-free days. Results: Multivariate analyses examining all five depression symptom dimensions simultaneously indicated that anhedonia was the only dimension to predict a longer time to remission, and also the only dimension to predict fewer depression-free days. In addition, when anhedonia and CDRS-total score were evaluated simultaneously, anhedonia continued to uniquely predict longer time to remission and fewer depression-free days. Conclusions: Anhedonia may represent an important negative prognostic indicator among treatment-resistant depressed adolescents. Further research is needed to elucidate neurobehavioral underpinnings of anhedonia, and to test treatments that target anhedonia in the context of overall treatment of depression. Clinical trial registration information--Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902. (Contains 3 tables.)
Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing ...toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.
We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated.
Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05).
This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We conducted a large surveillance study among members of an integrated healthcare delivery system in Pacific Northwest of the United States to estimate medical costs attributable to medically ...attended acute gastroenteritis (MAAGE) on the day care was sought and during 30-day follow-up. We used multivariable regression to compare costs of MAAGE and non-MAAGE cases matched on age, gender, and index time. Differences accounted for confounders, including race, ethnicity, and history of chronic underlying conditions. Analyses included 73,140 MAAGE episodes from adults and 18,617 from children who were Kaiser Permanente Northwest members during 2014-2016. Total costs were higher for MAAGE cases relative to non-MAAGE comparators as were costs on the day care was sought and costs during follow-up. Costs of MAAGE are substantial relative to the cost of usual-care medical services, and much of the burden accrues during short-term follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Anxiety and depression affect 30% of youth but are markedly undertreated compared with other mental disorders, especially in Hispanic populations. OBJECTIVE: To examine whether a ...pediatrics-based behavioral intervention targeting anxiety and depression improves clinical outcome compared with referral to outpatient community mental health care. DESIGN, SETTING, AND PARTICIPANTS: This 2-center randomized clinical trial with masked outcome assessment conducted between brief behavioral therapy (BBT) and assisted referral to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6, 2010, through December 5, 2014. Youths who met DSM-IV criteria for full or probable diagnoses of separation anxiety disorder, generalized anxiety disorder, social phobia, major depression, dysthymic disorder, and/or minor depression; lived with a consenting legal guardian for at least 6 months; and spoke English were included in the study. Exclusions included receipt of alternate treatment for anxiety or depression, presence of a suicidal plan, bipolar disorder, psychosis, posttraumatic stress disorder, substance dependence, current abuse, intellectual disability, or unstable serious physical illness. INTERVENTIONS: The BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy delivered in pediatric clinics by master’s-level clinicians. The ARC families received personalized referrals to mental health care and check-in calls to support accessing care from master’s-level coordinators. MAIN OUTCOMES AND MEASURES: The primary outcome was clinically significant improvement on the Clinical Global Impression–Improvement scale (score ≤2). Secondary outcomes included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale–Revised, and functioning. RESULTS: A total of 185 patients were enrolled in the study (mean SD age, 11.3 2.6 years; 107 57.8% female; 144 77.8% white; and 38 20.7% Hispanic). Youths in the BBT group (n = 95), compared with those in the ARC group (n = 90), had significantly higher rates of clinical improvement (56.8% vs 28.2%; χ21 = 13.09, P < .001; number needed to treat, 4), greater reductions in symptoms (F2,146 = 5.72; P = .004; Cohen f = 0.28), and better functioning (mean SD, 68.5 10.7 vs 61.9 11.9; t156 = 3.64; P < .001; Cohen d = 0.58). Ethnicity moderated outcomes, with Hispanic youth having substantially stronger response to BBT (76.5%) than ARC (7.1%) (χ21 = 14.90; P < .001; number needed to treat, 2). Effects were robust across sites. CONCLUSIONS AND RELEVANCE: A pediatric-based brief behavioral intervention for anxiety and depression is associated with benefits superior to those of assisted referral to outpatient mental health care. Effects were especially strong for Hispanic participants, suggesting that the protocol may be a useful tool in addressing ethnic disparities in care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01147614.
We tested whether augmenting conventional depression treatment in youth by treating sleep issues with cognitive behavioral therapy for insomnia (CBT-I) improved depression outcomes. We randomized ...youth 12–20 years of age to 10 weekly sessions of a sleep hygiene control condition (SH) combined with CBT for depression (CBT-D) (n = 20), or an experimental condition consisting of CBT-I combined with CBT-D (n = 21).
We assessed outcomes through 26 weeks of follow-up and found medium-large effects favoring the experimental CBT-I arm on some sleep outcomes (actigraphy total sleep time and Insomnia Severity Index “caseness”) and depression outcomes (higher percentage recovered, faster time to recovery), but little effect on other measures. Total sleep time improved by 99 min from baseline to week 12 in the CBT-I arm, but not in the SH arm. In addition, our pilot yielded important products to facilitate future studies: the youth-adapted CBT-I program; the study protocol; estimates of recruitment, retention, and attrition; and performance and parameters of candidate outcome measures.
ClinicalTrials.gov Identifier NCT00949689
•Unipolar depression is a common and impairing disorder in adolescence.•Insomnia is commonly comorbid with depression.•Adding CBT for insomnia to CBT for depression, improved sleep and depression outcomes with medium to large effect sizes.
Expanded carrier screening can provide risk information for numerous conditions. Understanding how individuals undergoing preconception expanded carrier screening value this information is important. ...The NextGen study evaluated the use of genome sequencing for expanded carrier screening and reporting secondary findings, and we measured participants' willingness to pay for this approach to understand how it is valued by women and couples planning a pregnancy.
We assessed 277 participants' willingness to pay for genome sequencing reporting carrier results for 728 gene/condition pairs and results for 121 secondary findings. We explored the association between attitudes and demographic factors and willingness to pay for expanded carrier screening using genome sequencing and conducted interviews with 58 of these participants to probe the reasoning behind their preferences.
Most participants were willing to pay for expanded carrier screening using genome sequencing. Willingness to pay was associated with income level and religiosity, but not risk status for a condition in the carrier panel. Participants willing to pay nothing or a small amount cited issues around financial resources, whereas those willing to pay higher amounts were motivated by "peace of mind" from carrier results.
Women and couples planning a pregnancy value genome sequencing. The potentially high out-of-pocket cost of this service could result in healthcare disparities, since maximum amounts that participants were willing to pay were higher than a typical copay and related to income.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Pediatric anxiety and depression are prevalent, impairing, and highly comorbid. Available evidence‐based treatments have an average response rate of 60%. One path to increasing response ...may be to identify likely non‐responders midway through treatment to adjust course prior to completing an episode of care. The aims of this study, thus, were to identify predictors of post‐intervention response assessing (a) mid‐treatment symptom severity, (b) session‐by‐session treatment process factors, and (c) a model optimizing the combination of these.
Method
Data were drawn from the treatment arm (N = 95, ages 8–16) of a randomized transdiagnostic intervention trial (Msessions = 11.2). Mid‐point measures of youth‐ and parent‐reported anxiety and depression were collected, and therapists rated homework completion, youth and parent engagement, and youth therapeutic alliance at each session. Logistic regression was used to predict response on the Clinical Global Impression Improvement Scale (CGI‐I ≤2) rated by independent evaluators masked to treatment condition.
Results
Mid‐point symptom measures were significant predictors of treatment response, as were therapist‐ratings of youth and parent engagement, therapeutic alliance, and homework completion. Therapist ratings were significant when tested as mean ratings summing across the first eight sessions of treatment (all ps < .004) and at individual session points (all ps <0.05). A combined prediction model included youth‐reported anxiety, parent‐reported depression, youth engagement at Session 2, and parent engagement at Session 8. This model correctly classified 76.5% of youth as non‐responders and 91.3% as responders at post‐treatment (Nagelkerke R2 = .59, χ2 (4, 80) = 46.54, p < .001).
Conclusion
This study provides initial evidence that response to transdiagnostic intervention for pediatric anxiety and depression may be reliably predicted by mid‐point. These data may serve as foundational evidence to develop adaptive treatment strategies to personalize intervention, correct treatment course, and optimize outcomes for youth with anxiety and depression.
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