VesiX cetylpyridinium chloride is rapidly bactericidal and reduces uropathogenic Escherichia coli bladder epithelial cell invasion in vitro.

Management of urinary tract infection (UTI) in postmenopausal women can be challenging. The recent rise in resistance to most of the available oral antibiotic options together with high recurrence rate in postmenopausal women has further complicated treatment of UTI. As such, intravesical instillations of antibiotics like gentamicin are being investigated as an alternative to oral antibiotic therapies. This study evaluates the efficacy of the candidate intravesical therapeutic VesiX, a solution containing the cationic detergent Cetylpyridinium chloride, against a broad range of uropathogenic bacterial species clinically isolated from postmenopausal women with recurrent UTI (rUTI). We also evaluate the cytotoxicity of VesiX against cultured bladder epithelial cells and find that low concentrations of 0.0063% and 0.0125% provide significant bactericidal effect toward diverse bacterial species including uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, and Proteus mirabilis while minimizing cytotoxic effects against cultured 5637 bladder epithelial cells. Lastly, to begin to evaluate the potential utility of using VesiX in combination therapy with existing intravesical therapies for rUTI, we investigate the combined effects of VesiX and the intravesical antibiotic gentamicin. We find that VesiX and gentamicin are not antagonistic and are able to reduce levels of intracellular UPEC in cultured bladder epithelial cells. IMPORTANCE: When urinary tract infections (UTIs), which affect over 50% of women, become resistant to available antibiotic therapies dangerous complications like kidney infection and lethal sepsis can occur. New therapeutic paradigms are needed to expand our arsenal against these difficult to manage infections. Our study investigates VesiX, a Cetylpyridinium chloride (CPC)-based therapeutic, as a candidate broad-spectrum antimicrobial agent for use in bladder instillation therapy for antibiotic-resistant UTI. CPC is a cationic surfactant that is FDA-approved for use in mouthwashes and is used as a food additive but has not been extensively evaluated as a UTI therapeutic. Our study is the first to investigate its rapid bactericidal kinetics against diverse uropathogenic bacterial species isolated from postmenopausal women with recurrent UTI and host cytotoxicity. We also report that together with the FDA-approved bladder-instillation agent gentamicin, VesiX was able to significantly reduce intracellular populations of uropathogenic bacteria in cultured bladder epithelial cells.

Malpractice Trends Involving Active Surveillance Across Cancers.

OBJECTIVE: To characterize malpractice trends related to active surveillance (AS) as a treatment strategy across cancers. BACKGROUND: Active surveillance is increasingly considered a viable management strategy for low-risk cancers. Since a subset of AS cases will progress, metastasize, or exhibit cancer-related mortality, a significant barrier to implementation is the perceived risk of litigation from missing the window for cure. Data on malpractice trends across cancers are lacking. METHODS: Westlaw Edge and LexisNexis Advance databases were searched from 1990 to 2022 for malpractice cases involving active surveillance in conjunction with thyroid cancer, prostate cancer, kidney cancer, breast cancer, or lymphoma. Queries included unpublished cases, trial orders, jury verdicts, and administrative decisions. Data were compiled on legal allegations, procedures performed, and verdicts or settlements rendered. RESULTS: Five prostate cancer cases were identified that pertained to active surveillance. Two cases involved alleged deliberate indifference from AS as a management strategy but were ruled as following the appropriate standard of care. In contrast, 3 cases involved alleged physician negligence for not explicitly recommending AS as a treatment option after complications from surgery occurred. All cases showed documented informed consent for AS, leading to defense verdicts in favor of the physicians. No cases of AS-related malpractice were identified for other cancer types. CONCLUSIONS: To date, no evidence of successful malpractice litigation for active surveillance in cancer has been identified. Given the legal precedent detailed in the identified cases and increasing support across national guidelines, active surveillance represents a sound management option in appropriate low-risk cancers, with no increased risk of medicolegal exposure.

Sustained Increases in Cardiomyocyte Protein O-Linked ß-N-Acetylglucosamine Levels Lead to Cardiac Hypertrophy and Reduced Mitochondrial Function Without Systolic Contractile Impairment.

Background Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of O-linked ß-N acetylglucosamine (O-GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein O-GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology. Methods and Results Using a naturally occurring dominant-negative O-GlcNAcase (dnOGA) inducible cardiomyocyte-specific overexpression transgenic mouse model, we induced dnOGA in 8- to 10-week-old mouse hearts. We examined the effects of 2-week and 24-week dnOGA overexpression, which progressed to a 1.8-fold increase in protein O-GlcNAcylation. Two-week increases in protein O-GlcNAc levels did not alter heart weight or function; however, 24-week increases in protein O-GlcNAcylation led to cardiac hypertrophy, mitochondrial dysfunction, fibrosis, and diastolic dysfunction. Interestingly, systolic function was maintained in 24-week dnOGA overexpression, despite several changes in gene expression associated with cardiovascular disease. Specifically, mRNA-sequencing analysis revealed several gene signatures, including reduction of mitochondrial oxidative phosphorylation, fatty acid, and glucose metabolism pathways, and antioxidant response pathways after 24-week dnOGA overexpression. Conclusions This study indicates that moderate increases in cardiomyocyte protein O-GlcNAcylation leads to a differential response with an initial reduction of metabolic pathways (2-week), which leads to cardiac remodeling (24-week). Moreover, the mouse model showed evidence of diastolic dysfunction consistent with a heart failure with preserved ejection fraction. These findings provide insight into the adaptive versus maladaptive responses to increased O-GlcNAcylation in heart.

Prospective study of quantitative liver MRI in cystic fibrosis: feasibility and comparison to PUSH cohort ultrasound.

BACKGROUND: Pediatric radiologists can identify a liver ultrasound (US) pattern predictive of progression to advanced liver disease. However, reliably discriminating these US patterns remains difficult. Quantitative magnetic resonance imaging (MRI) may provide an objective measure of liver disease in cystic fibrosis (CF). OBJECTIVE: The purpose of this study was to determine if quantitative MRI, including MR elastography, is feasible in children with CF and to determine how quantitative MRI-derived metrics compared to a research US. MATERIALS AND METHODS: A prospective, multi-institutional trial was performed evaluating CF participants who underwent a standardized MRI. At central review, liver stiffness, fat fraction, liver volume, and spleen volume were obtained. Participants whose MRI was performed within 1 year of US were classified by US pattern as normal, homogeneous hyperechoic, heterogeneous, or nodular. Each MRI measure was compared among US grade groups using the Kruskal-Wallis test. RESULTS: Ninety-three participants (51 females [54.8%]; mean 15.6 years [range 8.1-21.7 years]) underwent MRI. MR elastography was feasible in 87 participants (93.5%). Fifty-eight participants had an US within 1 year of MRI. In these participants, a nodular liver had significantly higher stiffness (P<0.01) than normal or homogeneous hyperechoic livers. Participants with a homogeneous hyperechoic liver had a higher fat fraction (P<0.005) than others. CONCLUSION: MR elastography is feasible in children with CF. Participants with a nodular pattern had higher liver stiffness supporting the US determination of advanced liver disease. Participants with a homogeneous hyperechoic pattern had higher fat fractions supporting the diagnosis of steatosis.

Knowledge, attitudes, and perceptions of hidradenitis suppurativa among young adults in Singapore.

Background: The prevalence of hidradenitis suppurativa (HS) is 0.00033% to 4.10% globally. Few epidemiological studies derive from Asia, with social stigmatization postulated to result in under-diagnosis. Objective: This study aimed to assess the self-reported prevalence of HS, and the knowledge, attitudes, and perceptions towards HS among Singaporean young-adults. Methods: A cross-sectional study (n = 158) was conducted by anonymous online questionnaire. The association between demographic factors and risk of potentially undiagnosed HS was evaluated using multivariable logistic regression. Differences between attitude-perception scores by demographic factors and knowledge of HS were tested using two-sample t-tests. Results: The prevalence of diagnosed and potentially undiagnosed HS was 0.63% and 8.9%, respectively. Non-Chinese had significantly higher social attitude-perception scores than Chinese (P = .029). Females had significantly higher social (P = .048) as well as economic and work (P = .037) attitude-perception scores than males. Those with knowledge of HS had significantly higher attitude-perception scores for interpersonal (P = .031) and social (P = .0052) subsections. Limitations: Small sample size, low frequency of HS cases, and self-reported prevalence may not generalize to the broader population in Singapore. Conclusion: Our results suggest a potential underdiagnosis of HS. Non-Chinese stigmatize HS less than Chinese, and females less than males. Individuals with knowledge of HS might be more open to interpersonal and social interactions with HS sufferers.

ChatGPT failed Taiwan's Family Medicine Board Exam.

BACKGROUND: Chat Generative Pre-trained Transformer (ChatGPT), OpenAI Limited Partnership, San Francisco, CA, USA is an artificial intelligence language model gaining popularity because of its large database and ability to interpret and respond to various queries. Although it has been tested by researchers in different fields, its performance varies depending on the domain. We aimed to further test its ability in the medical field. METHODS: We used questions from Taiwan's 2022 Family Medicine Board Exam, which combined both Chinese and English and covered various question types, including reverse questions and multiple-choice questions, and mainly focused on general medical knowledge. We pasted each question into ChatGPT and recorded its response, comparing it to the correct answer provided by the exam board. We used SAS 9.4 (Cary, North Carolina, USA) and Excel to calculate the accuracy rates for each question type. RESULTS: ChatGPT answered 52 questions out of 125 correctly, with an accuracy rate of 41.6%. The questions' length did not affect the accuracy rates. These were 45.5%, 33.3%, 58.3%, 50.0%, and 43.5% for negative-phrase questions, multiple-choice questions, mutually exclusive options, case scenario questions, and Taiwan's local policy-related questions, with no statistical difference observed. CONCLUSION: ChatGPT's accuracy rate was not good enough for Taiwan's Family Medicine Board Exam. Possible reasons include the difficulty level of the specialist exam and the relatively weak database of traditional Chinese language resources. However, ChatGPT performed acceptably in negative-phrase questions, mutually exclusive questions, and case scenario questions, and it can be a helpful tool for learning and exam preparation. Future research can explore ways to improve ChatGPT's accuracy rate for specialized exams and other domains.

Could directly shifting self-doubt mind-set reduce the negative effects of chronic self-doubt?

Research has shown negative effects of chronic self-doubt on psychological and performance outcomes. Two experiments were conducted to examine (a) the malleability of the mind-set about self-doubt; and (b) whether shifting to a more positive mind-set reduces the negative effects of self-doubt. Participants in Experiment 1 were randomly assigned to one of two mind-set induction conditions (positive versus negative). A control group was added in Experiment 2, in which we also enhanced the strength and symmetry of the positive and negative mind-set inductions. The results from both experiments showed a significant change in self-doubt mind-set in the hypothesized direction as a result of the mind-set induction. Interestingly, Experiment 2 revealed that priming either positive or negative mind-set diminished the negative self-doubt effects on task engagement, relative to the control group. The findings for the negative mind-set group were counter to the hypothesis but replicated what was observed in Experiment 1.

Expansion of the composition library for chemodiversity of hardwood extractives at molecular level by ultrahigh-resolution mass spectrometry.

To enhance the characterization of wood extractives at molecular level, a detailed ultrahigh-resolution mass spectrometry (UHRMS)-based analytical methodology was developed in this work. The analytical strategies, including selection of compatible solvent for extraction, evaluation of ionization solvent for effective electrospray ionization, and multi-dimensional data analysis, were established to ensure a comprehensive characterization of complex compositions in wood extractives. Extraction capability of seven solvents with varied polarities was examined by a standard reference material of hardwood biomass and evaluated based on thousands of compounds which were much more than those discovered before. With a variety of data-processing approaches, including compound type distribution, double bond equivalent versus carbon number plot, and van Krevelen diagram, the chemodiversity of the extractives was fully explored from different perspectives. This work greatly expanded the compound library of wood extractives and could also provide guidance for the integrated composition analysis of other biomass materials.

States' Merger Review Authority Is Associated With States Challenging Hospital Mergers, But Prices Continue To Increase.

States can challenge proposed hospital mergers by using antitrust laws to prevent anticompetitive harms. This observational study examined additional state laws-principally charitable trust, nonprofit corporation, health and safety, and certificate-of-need laws-that can serve as complements and substitutes for antitrust laws by empowering states to be notified of, review, and challenge proposed hospital mergers through administrative processes. During the period 2010-19, 862 hospital mergers were proposed, but only forty-two (4.9 percent) were challenged by states, including thirty-five by states without federal involvement, of which twenty-five (71.4 percent) originated in the eight states with the most robust merger review authority. The twenty-five challenges resulted in two mergers being blocked; three being abandoned; and twenty being approved with conditions, including seven with competitive-impact conditions. Hospital market concentration and prices increased at similar rates in these eight states versus other states, potentially because most challenges allowed mergers to proceed with conditions that did not adequately address competitive concerns. Although these findings do not reveal an optimal state framework, elements of advanced state merger review authority may have the potential to improve poorly functioning hospital markets.

The Economic Impact of Providing Evidence-Based Pediatric Mental Health Literacy Training to Primary Care Physicians.

OBJECTIVE: This paper presents a review of the current state of child and adolescent mental health literacy and provides current evidence of the economic impact of a pediatric mental health literacy (MHL) training program. METHODS: Employing a case-series-comparison design, physician referrals to urgent and specialized mental health services were linked with patient-specific information comparing referrals from MHL participants and non-participating physicians. The economic impact analysis was based on changes in the admitted referral frequency and lengths of stay for the MHL group, compared to themselves pretraining, and over the same time period compared to non-participating physicians. RESULTS: Average scheduled ambulatory admission rates per physician remained constant for trained and untrained pre-post groups. Average scheduled ambulatory admission wait time and length of stay reduced significantly post-training for MHL-trained physicians compared to pre-training and untrained physicians. In addition to reductions in length of stay, the total bed costs saving for emergency/inpatients admission deferrals was $2,932,112 or about $20,000 per MHL-trained physician. CONCLUSION: The estimated economic impact of the MHL training shows a substantial return on investment and supports wider implementation. The MHL training program should be a key feature of mental health reform strategies, as well as continuing and undergraduate medical education.

Comprehensive Composition, Structure, and Size Characterization for Thiophene Compounds in Petroleum Using Ultrahigh-Resolution Mass Spectrometry and Trapped Ion Mobility Spectrometry.

Thiophene compounds are the main concern of petroleum desulfurization, and their chemical composition and molecular configuration have critical impacts on thermodynamic and kinetic processes. In this work, atmospheric pressure chemical ionization (APCI) was employed for effective ionization of thiophene compounds in petroleum with complex matrix, in which carbon disulfide was used for generating predominant [M]+• ions without the need of derivatization as for electrospray ionization. APCI coupled with ultrahigh-resolution mass spectrometry (UHRMS) was successfully applied to the composition characterization of thiophene compounds in both a low boiling petroleum fraction and a whole crude oil. APCI coupled with trapped ion mobility spectrometry (TIMS) was developed to determine the shape and size of thiophene compounds, providing configuration information that affects the steric hindrance and diffusion behavior of reactants in the desulfurization reaction, which has not been previously reported. Moreover, the comprehensive experimental structural data, expressed as the collision cross section (CCS) of the ions as surrogates of molecules, provided clues to the factors affecting the desulfurization reactivity of thiophene compounds. Further exploration showed that not only qualitative analysis of thiophene compounds can be achieved from the correlation between m/z and CCS, but also molecular size was found to be correlated with CCS that can be used as structural analysis. Overall, the molecular composition and dimension analysis together can provide substantial information for the desulfurization activity of thiophene compounds, facilitating the desulfurization process studies and catalyst design.

Transperineal prostate biopsy identifies locations of clinically significant prostate cancer in men considering focal therapy with PI-RADS 3-5 regions of interest.

Objectives: To determine the benefit of performing transperineal prostate mapping biopsy (TPMB) following multiparametric magnetic resonance imaging (mpMRI) to increase the identification of clinically significant prostate cancer (csPCa) with Gleason grade group (GG) ≥ 2 and their locations outside of the PI-RADS v2 3-5 category lesions. Methods: mpMRI was performed in 80 men prior TPMB from two institutions. The mpMRI was considered clinically significant (csMRI) if it contained one or more PI-RADS 3-5 category lesion. mpMRI findings were compared against csPCa diagnosed by TPMB, performed between 16 November 2010, and 13 September 2019, for the entire gland, both lobes and to the right and left anterior and right and left posterior quadrants (RA, LA, RP and LP). Sensitivity, specificity, positive and negative predictive values (PPV, NPV), accuracy and the area under curve (AUC) were determined. Thirteen men also underwent radical prostatectomy and had comparison of TPMB pathology to prostatectomy specimen grading. Results: TPMB was positive in 60/80 (75%) of which 32 (53.3%) were csPCa. csPCa was present in the RA in 9 (11.3%), LA in 11 (13.8%), RP in 25 (31.3%) and LP in 27 (33.8%) and involved 1 quadrant in 7 (21.9%), 2 quadrants in 12 (37.5%), 3 quadrants in 11 (34.4%) and all 4 quadrants in 2 (6.3%) patients; 57/80 (71.3%) men had a mpMRIs with lesions designated as PI-RADS 3 in 24 (30%), 4 in 25 (31.3%) and 5 in 8 (10%). A csMRI was present in the RA in 7 (8.8%), LA in 8 (10%), RP in 31 (38.8%) and in the LP in 29 (36.3%), which were limited to one quadrant in 39 (68.4%), 2 quadrants in 16 (28.1%), and 3 quadrants in 2 (3.5%). Sensitivity, specificity, PPV, and NPV were determined from the results of the TPMB and were for the entire gland 81.3%, 35.4%, 45.6% and 73.9%. There were 31 csMRIs involving the right posterior of the gland but only 25 csPCa by TPMB of which 12/31 (38.7%) were concordant for high grade disease. There were 29 men who have a csMRI in the left posterior quadrant, and 14 (48.3%) were concordant with csPCa from the TPMB. Conclusions: MpMRI should be supplemented with TPMB to correctly identify the regions of the prostate that would require ablation in men considering focal therapy.

Emulsion-based encapsulation of pluripotent stem cells in hydrogel microspheres for cardiac differentiation.

Cardiovascular disease is the leading cause of death worldwide, and current treatments are ineffective or unavailable to majority of patients. Engineered cardiac tissue (ECT) is a promising treatment to restore function to the damaged myocardium; however, for these treatments to become a reality, tissue fabrication must be amenable to scalable production and be used in suspension culture. Here, we have developed a low-cost and scalable emulsion-based method for producing ECT microspheres from poly(ethylene glycol) (PEG)-fibrinogen encapsulated mouse embryonic stem cells (mESCs). Cell-laden microspheres were formed via water-in-oil emulsification; encapsulation occurred by suspending the cells in hydrogel precursor solution at cell densities from 5 to 60 million cells/ml, adding to mineral oil and vortexing. Microsphere diameters ranged from 30 to 570 µm; size variability was decreased by the addition of 2% poly(ethylene glycol) diacrylate. Initial cell encapsulation density impacted the ability for mESCs to grow and differentiate, with the greatest success occurring at higher cell densities. Microspheres differentiated into dense spheroidal ECTs with spontaneous contractions occurring as early as Day 10 of cardiac differentiation; furthermore, these ECT microspheres exhibited appropriate temporal changes in gene expression and response to pharmacological stimuli. These results demonstrate the ability to use an emulsion approach to encapsulate pluripotent stem cells for use in microsphere-based cardiac differentiation.

Non-invasive diagnostic criteria of hepatocellular carcinoma: Comparison of diagnostic accuracy of updated LI-RADS with clinical practice guidelines of OPTN-UNOS, AASLD, NCCN, EASL-EORTC, and KLSCG-NCC.

PURPOSE: To retrospectively compare the diagnostic performance of different noninvasive diagnostic criteria of HCC including LI-RADS, OPTN-UNOS, AASLD, NCCN, EASL-EORTC, KLCSG-NCC. MATERIALS AND METHODS: We reviewed the medical records of 3,491 pathologically examined liver lesions from January-2011 to January-2015 in our institution. 195 lesions in 133 patients (M:F = 100:33) with chronic hepatitis B/C and/or cirrhosis for any etiology were finally included in our study, with 98 lesions ≥ 2 cm, 72 lesions between 1-2 cm, and 25 lesions < 1 cm. The main comparison was made with the largest nodules of each patient (n = 133). The lesions were retrospectively evaluated for the diagnosis of HCC on DCE-CT or MR using different noninvasive diagnostic criteria including LI-RADS, OPTN-UNOS, AASLD, NCCN, EASL-EORTC, and KLCSG-NCC. With pathological evaluation serving as a gold-standard, sensitivity, specificity, PPV and NPV as well as accuracy of the diagnostic criteria were calculated. RESULTS: There was no statistically significant differences in diagnostic accuracy among noninvasive diagnostic criteria. For 133 lesions of the largest lesion per patient, the overall accuracy was highest with LI-RADS criteria (89.3%) and the overall sensitivity was highest with LI-RADS, AASLD, NCCN criteria (all 89.5%). For 1-2 cm lesions, sensitivity decreased for all criteria in the following order: EASL-EORTC (59.1%), KLCSG-NCC (58.3%), LI-RADS, AASLD, NCCN (all 56.5%), and OPTN-UNOS (22.7%) criteria. OPTN-UNOS had the highest specificity in cirrhotic livers, 91.7%. CONCLUSIONS: The current noninvasive diagnostic criteria of HCC have no statistically significant difference in diagnostic accuracy. Overall, LI-RADS had the highest sensitivity and accuracy among the guidelines. OPTN had the highest specificity for cirrhotic livers.

Arginine Starvation and Docetaxel Induce c-Myc-Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors.

PURPOSE: The response to acute and long-term arginine starvation results in a conditional adaptive metabolic reprogramming that can be harnessed for therapeutic opportunities in ASS1-negative tumors. Here, we investigate the underlying biology of priming ASS1- tumors with arginine deiminase (ADI-PEG20) before treatment with gemcitabine (GEM) and docetaxel (DTX) in sarcoma, pancreatic cancer, and melanoma cell lines. EXPERIMENTAL DESIGN: ASS1- tumor cell lines were treated to create LTAT (long-term ADI treated) cell lines (ASS1+) and used for drug combination studies. Protein expression of ASS1, dCK, RRM2, E2F1, c-MYC, and hENT1 was measured. c-MYC activity was determined, live-cell immunofluorescent studies for hENT1, uptake assays of FITC-cytosine probe, and rescue studies with a c-MYC inhibitor were all determined in the presence or absence of the ADI-PEG20:GEM:DTX. RESULTS: In examining modulations within the pyrimidine pathway, we identified that the addition of DTX to cells treated with ADI-PEG20 resulted in translocation of stabilized c-Myc to the nucleus. This resulted in an increase of hENT1 cell-surface expression and rendered the cells susceptible to GEM. In vivo studies demonstrate that the combination of ADI-PEG20:GEM:DTX was optimal for tumor growth inhibition, providing the preclinical mechanism and justification for the ongoing clinical trial of ADI-PEG20, GEM, and DTX in sarcoma. CONCLUSIONS: The priming of tumors with ADI-PEG20 and DTX results in the stabilization of c-MYC potentiating the effect of GEM treatment via an increase in hENT1 expression. This finding is applicable to ASS1-deficient cancers that are currently treated with GEM.

Response of Retinoic Acid in Patients with Radioactive Iodine-Refractory Thyroid Cancer: A Meta-Analysis.

PURPOSE: The purpose of this study was to evaluate the response of retinoic acid (RA) in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). METHODS: Systematic searches of MEDLINE (from inception to December 2016) and of EMBASE (from inception to December 2016) were performed for English-language publications on thyroid cancer treated with RA. Studies were classified according to the response criteria used: (1) 123I or 131I whole body scintigraphy (WBS), (2) serum thyroglobulin (Tg) level, (3) the response evaluation criteria in solid tumors (RECIST) version 1.0, and (4) World Health Organization (WHO) criteria. RESULTS: Disease response rates as determined by WBS ranged widely between 6.2% and 46.1% with a pooled disease response rate of 27.6% (95% confidence interval: 21.7-34.0%). Response rates as determined by Tg level ranged from 56.6% to 83.3% (pooled response rate 61.3% (51.0-70.9%)), RECIST response rates from 0% to 45.5% (pooled response rate 17.0% (1.4-44.5%)), and according to WHO criteria, the pooled response rate was 30.8% (12.7-52.7%). CONCLUSIONS: A minority of patients with RAI-refractory DTC respond to RA treatment.

Mental health literacy in primary care: Canadian Research and Education for the Advancement of Child Health (CanREACH).

The effectiveness of a continuing education programme in paediatric psychopharmacology designed for primary healthcare providers was objectively measured based on the assumption that training would lead to measurable changes in referral patterns and established clinical measures of referred patients. Using established, valid and reliable measures of clinical urgency embedded in to a regional healthcare system since 2002, the referrals to child and adolescent psychiatric services of physicians who participated in the training (n=99) were compared pretraining and post-training, and to non-participating/untrained referring physicians (n=7753) making referrals over the same time period. Referrals were analysed for evidence of change based on frequencies and measures of clinical urgency. Participants of the training programme also completed standardised baseline and outcome self-evaluations. Congruent with participants self-reported evaluative reports of improved knowledge and practice, analysis of referral frequency and the clinical urgency of referrals to paediatric psychiatric services over the study period indicated that trained physicians made more appropriate referrals (clinically more severe) and reduced referrals to emergency services. Quantitative clinical differences as completed by intake clinicians blind to referrals from the study group designations were observed within the trained physician group pretraining and post-training, and between the trained physician group and the unexposed physician group. The results illustrate a novel model for objectively measuring change among physicians based on training in paediatric mental health management.