Demographic, clinical, and service-use characteristics related to the clinician's recommendation to transition from child to adult mental health services.

PURPOSE: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians' advice to continue treatment at AMHS. METHODS: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians' transition recommendations. RESULTS: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. CONCLUSION: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures.

BACKGROUND: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. METHODS: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. DISCUSSION: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. TRIAL REGISTRATION: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Correction to: Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

Following publication of the original article [1], the authors reported they wanted to reinstate a co-author, who previously declined his authorship due to a misinterpretation of authorship limitations per research center.

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

BACKGROUND: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. METHODS: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. DISCUSSION: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Isolation and genetic analysis of pure cells from forensic biological mixtures: The precision of a digital approach.

Latest genotyping technologies allow to achieve a reliable genetic profile for the offender identification even from extremely minute biological evidence. The ultimate challenge occurs when genetic profiles need to be retrieved from a mixture, which is composed of biological material from two or more individuals. In this case, DNA profiling will often result in a complex genetic profile, which is then subject matter for statistical analysis. In principle, when more individuals contribute to a mixture with different biological fluids, their single genetic profiles can be obtained by separating the distinct cell types (e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different approaches have been investigated for this purpose, such as fluorescent-activated cell sorting (FACS) or laser capture microdissection (LCM), but currently none of these methods can guarantee the complete separation of different type of cells present in a mixture. In other fields of application, such as oncology, DEPArray™ technology, an image-based, microfluidic digital sorter, has been widely proven to enable the separation of pure cells, with single-cell precision. This study investigates the applicability of DEPArray™ technology to forensic samples analysis, focusing on the resolution of the forensic mixture problem. For the first time, we report here the development of an application-specific DEPArray™ workflow enabling the detection and recovery of pure homogeneous cell pools from simulated blood/saliva and semen/saliva mixtures, providing full genetic match with genetic profiles of corresponding donors. In addition, we assess the performance of standard forensic methods for DNA quantitation and genotyping on low-count, DEPArray™-isolated cells, showing that pure, almost complete profiles can be obtained from as few as ten haploid cells. Finally, we explore the applicability in real casework samples, demonstrating that the described approach provides complete separation of cells with outstanding precision. In all examined cases, DEPArray™ technology proves to be a groundbreaking technology for the resolution of forensic biological mixtures, through the precise isolation of pure cells for an incontrovertible attribution of the obtained genetic profiles.

Altered blood pressure variability in patients with congestive heart failure.

OBJECTIVE: Congestive heart failure (CHF) is characterized by sympathetic overactivity but reduced variability of heart interval and sympathetic nerve activity; little information exists, however, about the alterations in blood pressure variability in this syndrome, especially during excitatory manoeuvres such as tilting or exercise. DESIGN AND METHODS: Nine patients with CHF (age 62+/-1 years, NYHA class II-III, ejection fraction 33+/-1%, peak VO2 14.1+/-3.2 ml/min per kg body weight [mean +/- SEM]) and eight healthy control subjects (age 58+/-1 years) with normal left ventricular function were studied. Blood pressure (Finapres), R-R interval (ECG) and respiration (nasal thermistor) were recorded during 15-min periods of supine rest, 70 degree head-up tilting, submaximal bicycling exercise and post-exercise recovery. Total variance and the power of the spectral components of blood pressure (HF, respiratory-related; LF, 0.03-0.14 Hz; and VLF, 0.02-0.003 Hz) were measured. RESULTS: Compared with control subjects, CHF patients have, first, a normal overall blood pressure variability during supine rest but a failure to increase this variability in response to head-up tilt and exercise; second, a suppressed LF spectral component of blood pressure at rest and in response to head-up tilt and exercise; and third, reappearance of LF blood pressure power during postexercise recovery. CONCLUSIONS: In CHF patients, overall blood pressure variability and its LF spectral component are altered at rest and during sympathoexcitatory manoeuvres. Somewhat paradoxically, however, the depressed LF blood pressure power is partially restored during a 15-min recovery period, indicating that at least part of the CHF-related alterations of blood pressure variability have the potential to revert back towards normal under appropriate physiological circumstances.

Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications.

BACKGROUND: Little is known about the clinical, diagnostic, and prognostic aspects of upper-extremity deep vein thrombosis (UEDVT). OBJECTIVES: To identify the clinical and laboratory parameters associated with this disease, to assess the diagnostic accuracy of ultrasonographic methods for its detection, and to establish the frequency of both early and late complications. PATIENTS AND METHODS: After a careful history was taken, 58 consecutive patients with signs and symptoms that were clinically suggestive of UEDVT underwent the determination of antithrombin III and protein C and S levels and resistance to activated protein C and lupuslike anticoagulants. Compression ultrasonography, color flow Doppler imaging, and Doppler ultrasonography were performed prior to venography. Patients with confirmed UEDVT underwent objective tests to detect a pulmonary embolism and were followed up prospectively to record recurrent thromboembolic events and postthrombotic sequelae. RESULTS: Findings from venography confirmed UEDVT in 27 patients (47%). Central venous catheters, thrombophilic states, and a previous leg vein thrombosis were statistically significantly associated with UEDVT. Sensitivity and specificity of compression ultrasonography (96% and 93.5%, respectively) and color flow Doppler imaging (100% and 93%, respectively) were comparable and better than those of Doppler ultrasonography (81% and 77%, respectively). Objective findings suggestive of a pulmonary embolism were recorded in 36% of the patients with UEDVT. After a mean follow-up of 2 years, 2 patients with UEDVT experienced recurrent thromboembolic events, and 4 had postthrombotic sequelae. CONCLUSIONS: Symptomatic UEDVT is associated with central venous catheters, thrombophilic states, and a previous leg vein thrombosis. Both compression ultrasonography and color flow Doppler imaging are accurate methods for its detection. A pulmonary embolism is a common complication of the disease. Finally, this disorder may recur and may be followed by postthrombotic sequelae.

Echo Doppler color flow (EDCF) evaluation of vascular pathology in pediatric age groups.

Although rarely observed, vascular diseases in children constitute a complex clinical problem. Until recently the diagnostic approach to infant vascular diseases was based on invasive methods such as arteriography, but now the use of ultrasonographic methods such as Doppler c.w. and Echo Doppler Color Flow (EDCF) in angiology can offer new and interesting application even in the pediatric age range. In the present study 15 children affected by vascular diseases (eight with arteriovenous fistulas (AVF), two with pseudoaneurysms, and five with angiomas or cysts) either of iatrogenic or congenital etiology, were examined by Doppler c.w. and EDCF. In three additional cases a suspected vascular disease was not confirmed. The data obtained by Doppler c.w. and EDCF proved useful to perform a preoperative diagnosis; however some diagnostic criteria differed from those described in adulthood, as in the AVF cases, for instance, we observed the prevalence of indirect signs such as alterations of venous flow, and the presence of "multicolored speckled mass" and of "the spreading of the color in extravasal space" rather than a direct connection between an artery and a vein. Also pseudoaneurysms were easily detected by EDCF. In two cases of congenital AVF, the diagnosis was confirmed by arteriography. Surgery was performed in 9 children, 7 with AVF and 2 with pseudoaneurysm; in all cases, the vascular defect detected by ultrasonography was visualized and corrected. In 7 cases EDCF was also used in the follow-up. In conclusion this study suggests a possible more extensive use of ultrasonographic methods in the diagnostic approach to vascular diseases in pediatric age groups, and points out their validity in screening very young patients and in their surgical follow-up.

Diagnosis of high-grade stenosis of innominate artery.

Although pathology of the innominate artery (IA) is not frequent, it causes relevant impairment of extracranial circulation and sometimes cerebrovascular events. Definite differentiation of high-grade stenosis from occlusion of the IA has not been obtained until now with continuous-wave (C.W.) Doppler and duplex system ultrasound, and thus the direct evaluation of IA is not reliable by noninvasive methods. In this study the authors suggest an indirect method of evaluation of IA pathology based on the study of carotid, subclavian, and vertebral arteries (VA) with echo-Doppler-color-flow (EDCF) (with linear--phase array probes of 7.5 and 5 MHz). In the last two years they studied 6 patients with IA pathology (2 with occlusion (occ), 1 with stenosis of 80% and 3 with subocclusive stenosis > 90%). In both patients with occ, right VA flow was inverted, and also the right common carotid (CC) was involved (occ in 1 case and inverted flow in the other); in the 3 subocclusive stenoses a lowered systolic flow in the CC was recorded (48 vs 85 cm/sec, 41 vs 77, and 23 vs 109). In the 80% stenosis, besides the inverted flow in VA, only a reduced diastolic flow in CC was also recorded (19 vs 33 cm/sec measured in the left side). All patients with high grade stenosis were successfully confirmed by an angiographic study, including the different degree of stenosis. Five of the 6 patients underwent surgical correction with a restored flow in the previously involved artery. Only 1 patient with occlusion is waiting for surgical correction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Myocardial response to ischemia produced by repeated coronary occlusions: an experimental study]. / Risposta miocardica all'ischemia prodotta da occlusioni coronariche ripetute: studio sperimentale.

BACKGROUND: The fact that brief repeated episodes of ischemia may induce prolonged functional depression of the left ventricle is still a matter of debate. During an angioplasty several brief (20-90 sec) coronary occlusions are performed, with the potential risk of inducing myocardial jeopardy. METHODS: We performed 4 repeated LAD occlusions in 7 open chest pigs under general anesthesia and controlled ventilation. The following parameters were evaluated: mean systemic arterial pressure (MAP), left ventricular peak systolic pressure (LVPSP), heart rate (HR), and peak negative and positive dP/dt (dP/dt- and +). Each parameter was measured in the basal state and every 4 sec, in the expiratory phase, during the coronary occlusion, the first min and after 10 min of reperfusion. The percent change from control values for each parameter was also calculated and, by means of the ANOVA test, the differences among the 4 consecutive occlusions for each parameter were tested. RESULTS: The results showed that: 1) coronary occlusions significantly depressed dP/dt + and -, MAP and LVPSP, while HR did not change; 2) each variable returned to control values within 1 min of reperfusion; 3) the response to ischemia (percent change) was the same in each of the 4 consecutive occlusions for all parameters at every recording time. CONCLUSIONS: We can conclude that: 1) each experimental coronary occlusion induces a depression of myocardial function that is reversible in 1 min of reperfusion; 2) four repeated 2 minutes coronary occlusions do not induce cumulative effects on myocardial response to ischemia.

Takayasu's arteritis: anatomic change before and after steroid therapy evaluated by angiography and echo-Doppler color-flow.

A 36-year-old Italian woman with active Takayasu's disease presented a bilateral occlusions of subclavian artery and stenosis of bilateral common carotid arteries: the maximal diameter stenosis, measured with echo-Doppler color-flow (EDCF) in the longitudinal section was of 43.5 +/- 2.4% on the right and 61 +/- 1.4% on the left. Prednisolone was administered for 30 months at doses from 25 to 6 mg daily (12.5 mg every two days). During steroid therapy we could monitor by EDCF the anatomic change of the involved vessel and a final decrease in carotid wall thickening of 19.8% on the left and 14.0% on the right side. This work demonstrates for the first time that duplex sonography may be an useful tool to asses possible anatomic changes in the carotid lesions of Takayasu's arteritis in response to steroid therapy.

Electroretinographic changes in aged pigeons.

Photopic electroretinograms, either to full-field light flashes (FERGs) or to contrast-reversal of square-wave gratings (PERGs) have been recorded in pigeons aged 2 years old (n = 5) and 10 years old (n = 5). Mydriatic pupil diameter, ophthalmoscopic appearance of the retinal fundus and optic media, and refractive state were comparable in the two groups. V/log I functions of individual FERG components (a-wave, b-wave and oscillatory potentials) displayed significantly lower slopes in the old birds than in the young, which suggests a reduction in retinal gain. PERG amplitude also was significantly lower in the older birds over a wide range of spatial frequencies (0.2-8.8 c/deg). Estimated visual acuity based on the extrapolated high-frequency cut off was 18 c/deg in the younger birds and 7.8 c/deg in the older birds. These results are in agreement with psychophysical data and retinal age-related losses in visual acuity, photoreceptors and retinal ganglion cells. Since these findings are comparable to those reported for humans, the results suggest that pigeons may serve as a useful model for human visual aging.

[Effects of low-dose diltiazem on isovolumetric relaxation and contraction]. / Effetti del diltiazem, a basse dosi, su rilasciamento e contrazione isovolumetrica.

Calcium entry blockers are commonly believed to have a direct negative inotropic effect, but systolic function of the left ventricle (LV) can be improved when the peripheral vasodilator activity of the drug is present. The aim of our study was to evaluate the effect of diltiazem (D) on isovolumic contraction (IC) and relaxation (IR) at a dosage which is not effective on the peripheral vascular bed. We infused 10 micrograms/Kg/min i.v. of D for a 30 min period in to 12 pigs, anesthetized with ethyl urethane (1250 mg/Kg) and under artificial ventilation. The following variables were evaluated: left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressure, peak - and + dP/dt, mean arterial pressure (MAP), heart rate (HR) and double product. The recordings were obtained in the control condition and 5, 10, 15, 20, 25 and 30 minutes after beginning the infusion. The statistical analysis was performed using the one-way ANOVA test. Our results show: 1) a maximal increase in the peak + dP/dt from 2228 +/- 501 to 2448 +/- 576 mmHg/sec (p less than or equal to 0.01) and of the peak . dP/dt from 1262 +/- 260 to 1348 +/- 272 mmHg/sec (p less than or equal to 0.05); 2) and increase in LVSP from 86 +/- 13 to 90 +/- 10 mmHg (p less than or equal to 0.01) and 3) no changes in HR, PAM, LVEDP and double product. As the indices representing afterload and preload (PAM and LVEDP) remained unchanged during the infusion, we suggest that the increase in dP/dt + and - are due to a direct effect of diltiazem on myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonin depletion modifies the pigeon electroretinogram.

Significant amounts of endogenous serotonin have been detected in the retina of many nonmammalian vertebrates. In the pigeon retina, serotonin-like immunoreactivity has been localized within a subpopulation of bipolar and amacrine cells, and serotonin-containing terminals have been found to be segregated in different laminae of the inner plexiform layer. In the current experiments 5,7-dihydroxytryptamine was injected intravitreally in the pigeon eye in order to examine the effect of serotonin depletion on the functional activity of the retina. The physiological modifications induced by the serotonin depletion were examined by recording electroretinographic responses to light flashes of different intensity under conditions of light and dark adaptation. Our results show that 5,7-dihydroxytryptamine treatment selectively increases b-wave amplitude and modifies the function relating b-wave amplitude to Log flash intensity without affecting the peak latency and the amplitude of oscillatory potentials. These results can be interpreted in terms of a possible inhibitory role of serotonin on b-wave generators.

Efficacy of indobufen in the treatment of intermittent claudication.

The aim of this trial was to assess the activity of indobufen compared with placebo in peripheral occlusive arterial disease of the lower limbs of atherosclerotic or diabetic origin. Fifty-two outpatients were admitted to the randomized, double-blind study and were given either an indobufen 200-mg tablet (28 subjects) or placebo (24) for six months. Painfree walking distance on a treadmill at a constant speed (4 km/h) and slope (10 degrees) was assessed before and after three and six months' treatment. The painfree walking distance before treatment with indobufen or placebo averaged 153 +/- 23.02 (mean +/- SE) and 199 +/- 30.58 (mean +/- SE) meters respectively. After six months' treatment with active drug or placebo, this parameter reached 610 +/- 115.36 (p less than 0.01) and 243 +/- 32.49 (p greater than 0.05) meters respectively. The difference between the two treatments was statistically significant in favor of indobufen (p less than 0.01 Dunn's test).

[Digital radiology in the study of the lacrimal ducts]. / La radiologia digitale nello studio delle vie lacrimali.

The authors emphasize the usefulness of digital dacryocystography (DCG), as compared with various current techniques. Utilizing a radiographic unit equipped with a video-fluoroscopic system and interfaced to a digital video-processor, several digitalized images are acquired before, during and after the injection of contrast medium. Final images are obtained by subtraction of suitable pairs of source frames. Twenty-six patients affected by epiphora have been examined so far. In 21 cases digital subtraction DCG allowed an accurate visualization of the lacrimal system; in the other five patients the amount of information was acceptable. This methodology allows the assessment of both the normal anatomy of the lacrimal passages and their pathological patterns, such as obstructions, stenoses, fistulas, chronic dacryocystitis, lacrimal stones. The examination is easy and quick to perform, with no discomfort for the patient. Digital subtraction DCG proves thus to be a very valuable technique thanks to its possible electronic elaboration--i.e. the subtraction and the magnification of images--to its better contrast resolution, and to the possibility it yields of dynamic studies under radioscopic control.