The making of child and adolescent psychiatrists in Australia and New Zealand.

Child and adolescent psychiatry has an opportunity to adapt alongside the advancements in medical knowledge, post-graduate training, epidemiological realities and clinical service models. Here, we are guided by the mental health needs of our community's young and their families in our review of child and adolescent psychiatry training in Australia and New Zealand. We recognise that training must respond to clinical demand and service reform while ensuring a range of clinical and educational experiences to deliver expectable competencies in order to produce child and adolescent psychiatrists that meet the communities' needs now and in the future. We argue that training programmes be subject to rigorous evaluation by embedding continuing cycles of improvement including regular review and international bench marking.

Correction to: The child and adolescent psychiatry: study of training in Europe (CAP­STATE).

The original article has been corrected.

The child and adolescent psychiatry: study of training in Europe (CAP-STATE).

There is great cultural diversity across Europe. This is reflected in the organisation of child and adolescent mental health (CAMH) services and the training of the respective professionals in different countries in Europe. Patients and their parents will want a high quality, knowledgeable, and skillful service from child and adolescent psychiatrists (CAPs) wherever they see them in Europe. A European comparison of training programs allows all stakeholders in different European countries to assess the diversity and to initiate discussions as to the introduction of improvements within national training programs. Major issues to be addressed in comparing child and adolescent psychiatric training programs across Europe include: (1) formal organisation and content of training programs and the relationship to adult psychiatry and paediatrics; (2) flexibility of training, given different trainee interests and that many trainees will have young families; (3) quality of governance of training systems; (4) access to research; and (5) networking. The Child and Adolescent Psychiatry-Study of Training in Europe (CAP-State) is a survey of training for child and adolescent psychiatrists (CAPs) across European countries. It aims to revisit and extend the survey carried out in 2006 by Karabekiroglu and colleagues. The current article is embedded in a special issue of European Child + Adolescent Psychiatry attempting to for the first time address training in CAP at the European and global levels. Structured information was sought from each of 38 European and neighboring countries (subsequently loosely referred to as Europe) and obtained from 31. The information was provided by a senior trainee or recently qualified specialist and their information was checked and supplemented by information from a senior child and adolescent psychiatry trainer. Results showed that there is a very wide range of provision of training in child and adolescent psychiatry in different countries in Europe. There remains very substantial diversity in training across Europe and in the degree to which it is subject to national oversight and governance. Some possible reasons for this variation are discussed and some recommendations made.

Fractional flow reserve derived from CCTA may have a prognostic role in myocardial bridging.

PURPOSE: To evaluate the feasibility of fractional flow reserve (cFFR) derivation from coronary CT angiography (CCTA) in patients with myocardial bridging (MB), its relationship with MB anatomical features, and clinical relevance. METHODS: This retrospective study included 120 patients with MB of the left anterior descending artery (LAD) and 41 controls. MB location, length, depth, muscle index, instance, and stenosis rate were measured. cFFR values were compared between superficial MB (≤ 2 mm), deep MB (> 2 mm), and control groups. Factors associated with abnormal cFFR values (≤ 0.80) were analyzed. RESULTS: MB patients demonstrated lower cFFR values in MB and distal segments than controls (all p < 0.05). A significant cFFR difference was only found in the MB segment during systole between superficial (0.94, 0.90-0.96) and deep MB (0.91, 0.83-0.95) (p = 0.018). Abnormal cFFR values were found in 69 (57.5%) MB patients (29 [49.2%] superficial vs. 40 [65.6%] deep; p = 0.069). MB length (OR = 1.06, 95% CI 1.03-1.10; p = 0.001) and systolic stenosis (OR = 1.04, 95% CI 1.01-1.07; p = 0.021) were the main predictors for abnormal cFFR, with an area under the curve of 0.774 (95% CI 0.689-0.858; p < 0.001). MB patients with abnormal cFFR reported more typical angina (18.8% vs 3.9%, p = 0.023) than patients with normal values. CONCLUSION: MB patients showed lower cFFR values than controls. Abnormal cFFR values have a positive association with symptoms of typical angina. MB length and systolic stenosis demonstrate moderate predictive value for an abnormal cFFR value. KEY POINTS: • MB patients showed lower cFFR values than controls. • Abnormal cFFR values have a positive association with typical angina symptoms. • MB length and systolic stenosis demonstrate moderate predictive value for an abnormal cFFR value .

Modified calcium subtraction in dual-energy CT angiography of the lower extremity runoff: impact on diagnostic accuracy for stenosis detection.

OBJECTIVES: To investigate the diagnostic accuracy of a modified three-material decomposition calcium subtraction (CS) algorithm for the detection of arterial stenosis in dual-energy CT angiography (DE-CTA) of the lower extremity runoff compared to standard image reconstruction, using digital subtraction angiography (DSA) as the reference standard. METHODS: Eighty-eight patients (53 males; mean age, 65.9 ± 11 years) with suspected peripheral arterial disease (PAD) who had undergone a DE-CTA examination of the lower extremity runoff between May 2014 and May 2015 were included in this IRB-approved, HIPAA-compliant retrospective study. Standard linearly blended and CS images were reconstructed and vascular contrast-to-noise ratios (CNR) were calculated. Two independent observers assessed subjective image quality using a 5-point Likert scale. Diagnostic accuracy for ≥ 50% stenosis detection was analyzed in a subgroup of 45 patients who had undergone additional DSA. Diagnostic accuracy parameters were estimated with a random-effects logistic regression analysis and compared using generalized estimating equations. RESULTS: CS datasets showed higher CNR (15.3 ± 7.3) compared to standard reconstructions (13.5 ± 6.5, p < 0.001). Both reconstructions showed comparable qualitative image quality scores (CS, 4.64; standard, 4.57; p = 0.220). Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) for CS reconstructions was 96.5% (97.5%, 95.6%, 90.9%, 98.1) and 93.1% (98.8%, 90.4%, 82.3%, 99.1%) for standard images. CONCLUSIONS: A modified three-material decomposition CS algorithm provides increased vascular CNR, equivalent qualitative image quality, and greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff on DE-CTA compared with standard image reconstruction. KEY POINTS: • Calcified plaques may lead to overestimation of stenosis severity and false positive results, requiring additional invasive digital subtraction angiography (DSA). • A modified three-material decomposition algorithm for calcium subtraction provides greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff compared with standard image reconstruction. • The application of this algorithm in patients with heavily calcified vessels may be helpful to potentially reduce inconclusive CT angiography examinations and the need for subsequent invasive DSA.

Progression of coronary atherosclerotic plaque burden and relationship with adverse cardiovascular event in asymptomatic diabetic patients.

BACKGROUND: The heterogeneity of risk in patients with diabetes mellitus (DM) is acknowledged in new guidelines promulgating different treatment recommendations for diabetics at low cardiac risk. We performed a retrospective longitudinal follow-up study to evaluate coronary plaque progression and its impact on cardiac events in asymptomatic diabetic patients. METHODS: Data of 197 asymptomatic patients (63.1 ± 17 years, 60% males) with DM and suspected coronary artery disease (CAD) who underwent clinically indicated dual-source cardiac computed tomography (CT) were retrospectively analyzed. Patients with DM received standard of care treatment. Patients were classified into two groups based on CT coronary artery calcium scores (CACS): A, CACS> 10; B, CACS≤10. Progression of coronary plaque burden in both groups was evaluated and compared by baseline and follow-up coronary CT angiography (CCTA) using semi-automated plaque analysis and quantification software. Follow-up data were retrospectively gathered from medical records and endpoints of cardiac events were recorded via prospective phone-calls. The impacts of plaque composition and progression on cardiac events were specifically assessed. RESULTS: Patients with CACS> 10 showed an increase in dense coronary calcium volume, while patients with CACS≤10 had a more pronounced increase in the volume of low-attenuation "lipid-rich" plaque components between CCTA acquisitions. The composite endpoint occurred in 20 patients (10.2%) after a median follow-up period of 41.8 months. Furthermore, at follow-up CCTA, the presence of CACS> 10 (adjusted odds ratio, 0.701; 95% CI, 0.612-0.836), increase of dense calcium volume (OR, 0.860 95% CI, 0.771-0.960), and lipid volume (OR, 1.013; 95% CI, 1.007-1.020) were all independent predictors of cardiac events. CONCLUSION: Asymptomatic patients with DM experienced plaque progression as well as progression to "overt or silent CAD". The relative increase in plaque volume was associated with subsequent cardiac events, and the coronary calcification seemed to be inversely related to the outcome in asymptomatic diabetic patients.

High-pitch low-voltage CT coronary artery calcium scoring with tin filtration: accuracy and radiation dose reduction.

OBJECTIVES: To investigate diagnostic accuracy and radiation dose of high-pitch CT coronary artery calcium scoring (CACS) with tin filtration (Sn100kVp) versus standard 120kVp high-pitch acquisition. METHODS: 78 patients (58% male, 61.5±9.1 years) were prospectively enrolled. Subjects underwent clinical 120kVp high-pitch CACS using third-generation dual-source CT followed by additional high-pitch Sn100kVp acquisition. Agatston scores, calcium volume scores, Agatston score categories, percentile-based risk categorization and radiation metrics were compared. RESULTS: 61/78 patients showed coronary calcifications. Median Agatston scores were 34.9 [0.7-197.1] and 41.7 [0.7-207.2] and calcium volume scores were 34.1 [0.7-218.0] for Sn100kVp and 35.7 [1.1-221.0] for 120kVp acquisitions, respectively (both p<0.0001). Bland-Altman analysis revealed underestimated Agatston scores and calcium volume scores with Sn100kVp versus 120kVp acquisitions (mean difference: 16.4 and 11.5). However, Agatston score categories and percentile-based risk categories showed excellent agreement (ĸ=0.98 and ĸ=0.99). Image noise was 25.8±4.4HU and 16.6±2.9HU in Sn100kVp and 120kVp scans, respectively (p<0.0001). Dose-length-product was 9.9±4.8mGy*cm and 40.9±14.4mGy*cm with Sn100kVp and 120kVp scans, respectively (p<0.0001). This resulted in significant effective radiation dose reduction (0.13±0.07mSv vs. 0.57±0.2mSv, p<0.0001) for Sn100kVp acquisitions. CONCLUSION: CACS using high-pitch low-voltage tin-filtered acquisitions demonstrates excellent agreement in Agatston score and percentile-based cardiac risk categorization with standard 120kVp high-pitch acquisitions. Furthermore, radiation dose was significantly reduced by 78% while maintaining accurate risk prediction. KEY POINTS: • Coronary artery calcium scoring with tin filtration reduces radiation dose by 78%. • There is excellent correlation between high-pitch Sn100kVp and standard 120kVp acquisitions. • Excellent agreement regarding Agatston score categories and percentile-based risk categorization was achieved. • No cardiac risk reclassifications were observed using Sn100kVp coronary artery calcium scoring.

Diagnostic accuracy of low and high tube voltage coronary CT angiography using an X-ray tube potential-tailored contrast medium injection protocol.

OBJECTIVES: To compare the diagnostic accuracy between low-kilovolt peak (kVp) (≤ 100) and high-kVp (> 100) third-generation dual-source coronary CT angiography (CCTA) using a kVp-tailored contrast media injection protocol. METHODS: One hundred twenty patients (mean age = 62.6 years, BMI = 29.0 kg/m2) who underwent catheter angiography and CCTA with automated kVp selection were separated into two cohorts (each n = 60, mean kVp = 84 and 117). Contrast media dose was tailored to the kVp level: 70 = 40 ml, 80 = 50 ml, 90 = 60 ml, 100 = 70 ml, 110 = 80 ml, and 120 = 90 ml. Contrast-to-noise ratio (CNR) was measured. Two observers evaluated image quality and the presence of significant coronary stenosis (> 50% luminal narrowing). RESULTS: Diagnostic accuracy (sensitivity/specificity) with ≤ 100 vs. > 100 kVp CCTA was comparable: per patient = 93.9/92.6% vs. 90.9/92.6%, per vessel = 91.5/97.8% vs. 94.0/96.8%, and per segment = 90.0/96.7% vs. 90.7/95.2% (all P > 0.64). CNR was similar (P > 0.18) in the low-kVp vs. high-kVp group (12.0 vs. 11.1), as ws subjective image quality (P = 0.38). Contrast media requirements were reduced by 38.1% in the low- vs. high-kVp cohort (53.6 vs. 86.6 ml, P < 0.001) and radiation dose by 59.6% (4.3 vs. 10.6 mSv, P < 0.001). CONCLUSIONS: Automated tube voltage selection with a tailored contrast media injection protocol allows CCTA to be performed at ≤ 100 kVp with substantial dose reductions and equivalent diagnostic accuracy for coronary stenosis detection compared to acquisitions at > 100 kVp. KEY POINTS: • Low-kVp coronary CT angiography (CCTA) enables reduced contrast and radiation dose. • Diagnostic accuracy is comparable between ≤ 100 and > 100 kVp CCTA. • Image quality is similar for low- and high-kVp CCTA. • Low-kVp image acquisition is facilitated by automated tube voltage selection. • Tailoring contrast injection protocols to the automatically selected kVp-level is feasible.

Rare Examples of Fe(IV) Alkyl-Imide Migratory Insertions: Impact of Fe-C Covalency in (Me2IPr)Fe(═NAd)R2 (R = neoPe, 1-nor).

The iron(IV) imide complexes, (Me2IPr)-R2Fe=NAd (R = neoPe (3a), 1-nor (3b)) undergo migratory insertion to iron(II) amides (Me2IPr)RFe{NR(Ad)} (R = neoPe (4a), 1-nor (4b)) without evidence of imidyl or free nitrene character. By increasing the field strength about iron, odd-electron reactivity was circumvented via increased covalency.

Correlation and predictive value of aortic root calcification markers with coronary artery calcification and obstructive coronary artery disease.

OBJECTIVE: To evaluate the correlation between aortic root calcification (ARC) markers and coronary artery calcification (CAC) derived from coronary artery calcium scoring (CACS) and their ability to predict obstructive coronary artery disease (CAD). METHODS: We retrospectively analyzed 189 patients (47% male, age 60.3 ± 11.1 years) with an intermediate probability of CAD who underwent clinically indicated CACS and coronary CT angiography (CCTA). ARC markers [aortic root calcium score (ARCS) and volume (ARCV)] were calculated and compared to CAC markers: coronary artery calcium score (CACS), volume (CACV), and mass (CACM). CCTA datasets were visually evaluated for significant CAD (stenosis ≥ 50%) and the ability of ARC markers to predict obstructive CAD was assessed. RESULTS: ARCS (mean 67.7 ± 189.5) and ARCV (mean 67.3 ± 184.7) showed significant differences between patients with and without CAC (109.4 ± 238.6 vs 9.42 ± 31.4, p < 0.0001; 108.5 ± 232.4 vs 9.9 ± 30.5, p < 0.0001). A strong correlation was found for ARCS and ARCV with CACS, CACM, and CACV (all p < 0.0001). In a multivariate analysis, ARCS (OR 1.09, p = 0.033) and ARCV (OR 1.12, p = 0.046) were independent markers for CAC. Using a receiver-operating characteristics analysis, the AUC to detect severe CAC was 0.71 (p < 0.0001) and 0.71 (p < 0.0001) for ARCS and ARCV, respectively. ARCS (0.67, p < 0.0001) and ARCV (0.68, p < 0.0001) showed discriminatory power for predicting obstructive CAD, yielding sensitivities 61 and 78% and specificities of 62 and 80%, respectively. CONCLUSION: ARC markers are associated with and independently predict the presence of CAC and obstructive CAD. Further testing is required in patients with severe ARC and significant CAD in order to reliably obtain these markers from thoracic-CT or X-ray for proper risk classification.

Oxidatively Triggered Carbon-Carbon Bond Formation in Ene-amide Complexes.

Ene-amides have been explored as ligands and substrates for oxidative coupling. Treatment of CrCl2, Cl2Fe(PMe3)2, and Cl2Copy4 with 2 equiv of {(2,6-(i)Pr2C6H3)(1-(c)Hexenyl)N}Li afforded pseudosquare planar {η(3)-C,C,N-(2,6-(i)Pr2C6H3)(1-(c)Hexenyl)N}2Cr (1-Cr, 78%), trigonal {(2,6-(i)Pr2C6H3)(1-(c)Hexenyl)N}2Fe(PMe3) (2-Fe, 80%), and tetrahedral {(2,6-(i)Pr2C6H3)(1-(c)Hexenyl)N}2Co(py)2 (3-Co, 91%) in very good yields. The addition of CrCl3 to 1-Cr, and FeCl3 to 2-Fe, afforded oxidatively triggered C-C bond formation as rac-2,2'-di(2,6-(i)Pr2C6H3N═)2dicyclohexane (EA2) was produced in modest yields. Various lithium ene-amides were similarly coupled, and the mechanism was assessed via stoichiometric reactions. Some ferrous compounds (e.g., 2-Fe, FeCl2) were shown to catalyze C-arylation of {(2,6-(i)Pr2C6H3)(1-(c)Hexenyl)N}Li with PhBr, but the reaction was variable. Structural characterizations of 1-Cr, 2-Fe, and 3-Co are reported.

Effect of a Real-Time Pediatric ICU Safety Bundle Dashboard on Quality Improvement Measures.

BACKGROUND: Patient daily goal sheets have been shown to improve compliance with hospital policies but might not represent the dynamic nature of care delivery in the pediatric ICU (PICU) setting. A study was conducted at Children's National Health System (Washington, DC) to determine the effect of a visible, unitwide, real-time dashboard on timeliness of compliance with quality and safety measures. METHODS: An automated electronic health record (EHR)- querying tool was created to assess compliance with a PICU Safety Bundle. Querying of the EHR for compliance and updating of the dashboard automatically occurred every five minutes. A real-time visual display showed data on presence of consent for treatment, restraint orders, presence of urinary catheters, deep venous thrombosis (DVT) prophylaxis, Braden Q score, and medication reconciliation. Baseline compliance and duration of noncompliance was established during three time periods: the first, before activation of the dashboard; the second, at one month following activation of the dashboard; and the third, at three months after activation. RESULTS: A total of 450 patients were included in the analysis. Between the first and third time periods, the median time from PICU admission to obtaining treatment consent decreased by 49%, from 393 to 202 minutes (p=.05). The number of patients with urinary catheters in place>96 hours decreased from 16 (32%) in Period 1 to 11 (19%) for Periods 2 and 3 combined (p=.01). Completion of medication reconciliation improved from 80% in the first time period to 93% and 92%, respectively, in the subsequent two periods (p=.002). There was no difference between the three periods in presence of restraint orders, DVT prophylaxis, or development or worsening of pressure ulcers. CONCLUSIONS: A unitwide dashboard can increase awareness for potential interventions, affecting patient safety in the PICU in a dynamic manner.

Determination of psychosis-related clinical profiles in children with autism spectrum disorders using latent class analysis.

In children with autism spectrum disorders (ASD), high rates of idiosyncratic fears and anxiety reactions and thought disorder are thought to increase the risk of psychosis. The critical next step is to identify whether combinations of these symptoms can be used to categorise individual patients into ASD subclasses, and to test their relevance to psychosis. All patients with ASD (n = 84) admitted to a specialist national inpatient unit from 2003 to 2012 were rated for the presence or absence of impairment in affective regulation and anxiety (peculiar phobias, panic episodes, explosive reactions to anxiety), social deficits (social disinterest, avoidance or withdrawal and abnormal attachment) and thought disorder (disorganised or illogical thinking, bizarre fantasies, overvalued or delusional ideas). Latent class analysis of individual symptoms was conducted to identify ASD classes. External validation of these classes was performed using as a criterion the presence of hallucinations. Latent class analysis identified two distinct classes. Bizarre fears and anxiety reactions and thought disorder symptoms differentiated ASD patients into those with psychotic features (ASD-P: 51 %) and those without (ASD-NonP: 49 %). Hallucinations were present in 26 % of the ASD-P class but only 2.4 % of the ASD-NonP. Both the ASD-P and the ASD-NonP class benefited from inpatient treatment although inpatient stay was prolonged in the ASD-P class. This study provides the first empirically derived classification of ASD in relation to psychosis based on three underlying symptom dimensions, anxiety, social deficits and thought disorder. These results can be further developed by testing the reproducibility and prognostic value of the identified classes.

Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

OBJECTIVE: Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. DESIGN: Prospective, blinded, randomized, controlled, multicenter trial. SETTING: PICU. PATIENTS: Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. CONCLUSIONS: Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Hypoglycemia adverse events in PICUs and cardiac ICUs: differentiating preventable and nonpreventable events*.

OBJECTIVES: To describe the use of an adverse event detection system to identify, characterize, and categorize preventable versus nonpreventable hypoglycemia AEs in PICUs and cardiac ICUs. DESIGN: Retrospective observational study. SETTING: PICU and cardiac ICU of a tertiary pediatric hospital. SUBJECTS: All hypoglycemia triggers generated over a 3-year period. INTERVENTIONS: All hypoglycemia triggers generated via an electronic health record-driven surveillance system were investigated to determine if they represented a true adverse event and if that event was preventable or nonpreventable. Clinical and demographic variables were analyzed to identify characteristics of patients who developed a preventable or nonpreventable hypoglycemia adverse event. MEASUREMENTS AND MAIN RESULTS: There were 197 hypoglycemia adverse events in 90 patients. Thirty percent of the adverse events in the PICU and 36% of the adverse events in the cardiac ICU were characterized as preventable. Of the adverse events, 118 (59.9%) necessitated an intravenous dextrose bolus. No adverse events were associated with reporting of symptoms of hypoglycemia including apnea, altered mental status, or seizures. Events were more likely to be preventable (p < 0.001) if the patient was receiving only parenteral sources of nutrition (intravenous fluids or total parenteral nutrition). Controlling for weekends and holidays, adverse events associated with sole parenteral nutrition source had an increased odds ratio of 9.5 (95% confidence interval: 2.8-31.9) of being preventable. Stratifying by ICU, cardiac ICU events occurring on a weekend or holiday were more likely to be preventable (p = 0.001). Stratifying by unit and controlling for parenteral nutrition source, adverse events in the cardiac ICU occurring on weekends or holidays had an increased odds ratio of 11.6 (95% confidence interval: 2.7-50.2) of being preventable. CONCLUSIONS: Preventable hypoglycemia adverse events are associated with patients receiving sole parenteral sources of nutrition in both the PICU and cardiac ICU. In the cardiac ICU, there is an association between weekend and holiday time periods and the development of preventable hypoglycemia adverse events.

A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PURPOSE: To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). MATERIALS AND METHODS: Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. RESULTS: Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. CONCLUSIONS: Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs.