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Monoclonal antibodies in nuclear medicine.

Monoclonal antibodies have been a part of biomedical research for nearly a decade, yet a comparable period of time may be required before radiolabeled monoclonal antibodies come into standard practice in the diagnosis and therapy of human disease. Difficulties in identifying appropriate antigens, developing the optimal antibody species, attaching the most effective radiolabel and choosing the best method of administration all confound present investigations. The problems confronting therapeutic applications are, for the most part, an extension of those associated with diagnostic techniques. Still, there is much well-deserved optimism, and progress in all areas of investigation will ultimately come together to resolve most if not all of these problems. It is inevitable that monoclonal antibodies will have significant impact on the practice of nuclear medicine, and presented here is a review of the basic knowledge as well as an update on the current status of radiolabeled monoclonal antibodies in medicine.

Animals↗

Interest of a prescreening questionnaire to reduce the cost of bone densitometry.

Bone mineral density (BMD) measurement is widely recognized as the best single tool to identify patients with a high lifetime risk of developing an osteoporosis-related fracture. However, the cost/benefit value of screening the whole population has been repeatedly challenged and demonstrated to be rather poor. In many countries, BMD scan is not or no longer reimbursed because of lack of validated criteria to identify patients who should benefit from this procedure. Based on the proposals of a nationwide expert panel, a simple questionnaire identifying historical, clinical and behavioral risk factors for osteoporosis was developed. The aim of this study was to assess the diagnostic accuracy of the proposed criteria; to determine the extent to which this questionnaire could be useful for optimizing the use of densitometry tests; and, more specifically, to estimate the diagnostic costs per osteoporotic or osteopenic patient detected. For this purpose, we applied the questionnaire to 3998 consecutive individuals at least 20 years old, of both genders, either consulting spontaneously or referred for a BMD measurement to an outpatient osteoporosis center. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip (both total hip and femoral neck). Diagnostic accuracies were evaluated through measures of sensitivity, specificity, and positive and negative predictive values. After determining a benchmark value for age, different strategies were compared in order to identify the most cost-effective one in terms of cost per patient detected. According to the WHO operational definition of osteoporosis (T-score <-2.5), 31% of the subjects were classified as osteoporotic at one or more of the measured sites. If only patients with at least one of the proposed risk factors had been referred for scans, 33.3% of the BMD measurements would have been avoided. Among those, less than 5% were missclassified as they did have osteoporosis at the total hip and up to 23% at one or more of the considered sites. On the other hand, of the subjects who would be recommended for a densitometry test, only a small fraction were identified correctly (the positive predictive values varied from 11.3% at the total hip to 34.8% at any site). In this first setting, the suggested criteria seem useful chiefly for excluding subjects who do not need a DXA scan rather than selecting osteoporotic patients. When applied only to patients aged 61 years or more, the positive predictive values rose to 15.1% (total hip) and 42.9% (any site), whereas the corresponding negative predictive values were set at 93% and 68.6%. In comparison, with a mass screening scenario the estimated diagnostic costs (costs associated with the DXA procedure) per osteoporotic patient detected at any of the considered sites would be reduced by more than 9% (59.4 instead of 65.3 Euros) if the suggested indications are taken into account for prescreening patients. And when the questionnaire is applied only to women over the age of 60 years these costs would be further reduced to 50.6 Euros, representing a 23% decrease. Then, a prescreening strategy based on these indications concomitantly with an age-selective criterion could represent a promising way toward a more rational use of BMD measurement.

Absorptiometry, Photon↗

MR imaging of the adult elbow.

Magnetic resonance (MR) imaging can provide important diagnostic information in the evaluation of the adult elbow. Optimal imaging technique should include the use of proper positioning, surface coils, and appropriate sequences and imaging planes as indicated by the suspected abnormalities. A familiarity with the anatomy of the normal elbow is crucial to identifying pathologic entities correctly and avoiding diagnostic pitfalls. Disruption of the collateral ligaments can best be demonstrated with thin-section coronal gradient-echo MR images. Injuries to the flexor and extensor muscle groups, biceps muscles, and triceps muscles require T2-weighted or short-inversion-time inversion recovery (STIR) MR images in the long and short axes of the affected muscle. The evaluation of osteochondral lesions and intraarticular bodies is optimized with T1-weighted and STIR MR images. Synovial processes usually necessitate the intravenous administration of gadopentetate dimeglumine to distinguish joint fluid from pannus. The contents of the cubital tunnel are best visualized on axial T1-weighted and STIR MR images. Masses arising in or near the elbow should be imaged with multiple sequences in at least two planes, and involvement of adjacent vital structures should be carefully evaluated.

Adult↗

Detection of classical swine fever virus in archival formalin-fixed tissues by reverse transcription-polymerase chain reaction.

Classical swine fever (CSF) is an economically important Office International des Epizooties list A disease of swine. Inadequate diagnostic infrastructure in developing countries may sometimes make the conduit of viable samples to diagnostic laboratories difficult and at times formalin-fixed tissues may be the only morbid materials available which are not amenable to most laboratory tests. The potential diagnostic abilities in such situations would be enhanced if a highly sensitive and specific method as reverse transcription-polymerase chain reaction (RT-PCR) could be applied to such samples. In the present study, archival formalin-fixed CSF samples were subjected to successful RT-PCR amplification of a 172-bp fragment from E2/NS2 region of CSFV genome. The fidelity of amplification was established by a dot-blot hybridization assay employing a homologous biotinylated cDNA probe. The optimized procedure may be resorted to as a diagnostic tool if viable samples are unavailable and may have the potential to facilitate retrospective studies on archival samples.

Animals↗

Competing practice guidelines: using cost-effectiveness analysis to make optimal decisions.

In this paper, cost and effectiveness data for six clinical interventions are applied simultaneously to a hypothetical population of 100,000 patients to show how selecting guidelines to maximize overall population benefit compares with selecting the best guidelines for individual patients. By entering effectiveness (added survival) and cost information from recent prevention, screening, diagnostic, and therapeutic guidelines into a computer-based optimization model, the options that maximized overall population effectiveness while keeping additional cost within varying specified constraints were identified. In 57% of selection opportunities, the clusters of guidelines that yielded maximum population benefit differed from those that maximized benefit for individual patients. Some choices were more stable than others over ranges of cost constraints. Clinical practice guidelines chosen to maximize cost-effectiveness for individual patients often do not maximize cost-effectiveness for populations of patients. To allocate resources as efficiently as possible, decision makers should consider other sources of information in addition to the recommendations of specific practice guidelines. "Robust" guidelines that simultaneously address both individual and societal health benefit should be sought.

Cost-Benefit Analysis↗

Artificial intelligence-assisted clinical exome sequencing: Insights and outcomes from 822 pediatric diagnoses.

PURPOSE: This retrospective study examined the clinical and genetic characteristics of pediatric patients undergoing clinical exome sequencing (ES) and evaluated the performance of a commercially available artificial intelligence (AI) platform that was integrated into our analysis pipeline. METHODS: ES was performed in 822 consecutive patients at a single clinical laboratory. AI-based tools were used to jointly assess genetic information and the proband's Human Phenotype Ontology terms to support variant prioritization during the initial case review. RESULTS: A definitive molecular diagnosis was established in 22% (181 of 822) of index cases, while 40% (325 of 822) had variants of uncertain significance. Among those with a definitive diagnosis, 93% (168 of 181) had a single finding and 7% (13 of 181) had multiple findings. Of the 152 reported pathogenic/likely pathogenic variants in the fully resolved cases, 98.7% were successfully flagged by AI, and 75.0% ranked among the top 10 "most likely" variants. CONCLUSION: Clinical ES provides a substantial diagnostic yield in complex pediatric disorders. Integration of AI-powered platforms can accelerate phenotype-driven variant prioritization and facilitate rare disease diagnostics, but underscores the need for careful validation and optimization in clinical workflows.

Artificial intelligence↗

A complete substitutional analysis of VIP for better tumor imaging properties.

Since numerous tumor cells overexpress the vasoactive intestinal peptide (VIP) receptor subtype 1 (VPAC(1)), VIP-dye conjugates would be useful as contrast agents for in vivo imaging. However, proteolytic degradation of VIP in vivo limits their diagnostic use and highlights the need for structurally optimized VIP derivatives with improved pharmacokinetics. Here, we applied parallel nano-synthesis of cleavable peptides on cellulose membranes to perform a complete VIP substitutional analysis. The resulting 504 different VIP-dye analogs were tested for cell binding by flow cytometry. They provided a detailed analysis of amino acid positions essential for binding to VPAC(1) overexpressing cells. A generalized VIP-dye binding motif derived from the substitutional analysis results served as a reference point for further optimization. An [Arg8]-VIP-dye analog showed increased stability towards proteolytic degradation, good tumor-to-tissue contrast in mice and a longer half-life in vivo.

Amino Acid Sequence↗

[The diagnostic approach in hepatic lesions--the role and place of laparoscopy with laparoscopic echography].

The study is designed to cases the potentials of laparoscopy with laparoscopic echography, and the role they play in the diagnostic algorithm, with the purpose to develop an optimal therapeutic approach to hepatic lesions. Laparoscope R. Wolf and 7.5 MHz linear transducer, obtained from the Aloka Company are employed in work. A total of 303 patients presenting primary and metastatic carcinoma of liver (58 and 145, respectively), cholangiocarcinoma (11), hemangioma(28), adenomatous hyperplasia (38) and other lesions (23) are studied. Morphologic verification of the diagnosis is done in over one third of cases. In 30 to 40 per cent of the series reviewed laparoscopic echography supplements the laparoscopic finding depending on the type of lesion. Without pretending to create a diagnostic algorithm in individual hepatic lesions, abiding to the following diagnostic approach is strongly recommended: stage one--echography (a noninvasive, not irradiating, cheap, readily accessible and often resolving method), stage two--noninvasive, stage three--invasive, stage four--preoperative or final (laparoscopy plus laparoscopic echography). In the event of properly established indications, the invasive methods of study (thin-needle biopsy under ultrasonographic control plus laparoscopy) may be considered as a second stage, without any need to apply the complete spectrum of examination accessible. Not infrequently, laparoscopy with laparoscopic ultrasonography play a crucial role in diagnosing liver lesions, exact determination of the stage and resectability of the neoplastic process, planning and shortening the duration of operation with simultaneous identification of intractable patients.

Algorithms↗

Effectiveness of current technology in the diagnosis and management of lower gastrointestinal hemorrhage.

Lower gastrointestinal hemorrhage is a common clinical problem for which multiple diagnostic tests and therapeutic interventions have been developed but no optimal approach has been established. We reviewed 107 consecutive patients admitted to the Massachusetts General Hospital for management of acute lower gastrointestinal hemorrhage to determine the effectiveness of diagnostic and management technologies, with particular attention to urgent colonoscopy. Colonoscopy yielded a diagnosis in 90% of patients, provided the opportunity for successful therapy in 9 of 13 patients (69%), and shortened hospital stay. Angiography performed after a scan positive for bleeding was often diagnostic, and angiography provided the means for successful therapy in 5 of 10 patients (50%). Barium enema and sigmoidoscopy had lower clinical yields. Although roles exist for other technologies, colonoscopy is the most convenient and effective first test in the evaluation of patients with significant lower gastrointestinal hemorrhage. Diagnostic yield, therapeutic opportunity, and cost effectiveness are maximized in early studies.

Acute Disease↗

Diagnostic properties of nerve conduction tests in population-based carpal tunnel syndrome.

BACKGROUND: Numerous nerve conduction tests are used for the electrodiagnosis of carpal tunnel syndrome (CTS), with a wide range of sensitivity and specificity reported for each test in clinical studies. The tests have not been assessed in population-based studies. Such information would be important when using electrodiagnosis in epidemiologic research. The purpose of this study was to compare the diagnostic accuracy of various nerve conduction tests in population-based CTS and determine the properties of the most accurate test. METHODS: In a population-based study a questionnaire was mailed to a random sample of 3,000 persons. Of 2,466 responders, 262 symptomatic (numbness/tingling in the radial fingers) and 125 randomly selected asymptomatic responders underwent clinical and electrophysiologic examinations. A standardized hand diagram was administered to the symptomatic persons. At the clinical examination, the examining surgeon identified 94 symptomatic persons as having clinically certain CTS. Nerve conduction tests were then performed on the symptomatic and the asymptomatic persons by blinded examiners. Analysis with receiver operating characteristic (ROC) curves was used to compare the diagnostic accuracy of the nerve conduction tests in distinguishing the persons with clinically certain CTS from the asymptomatic persons. RESULTS: No difference was shown in the diagnostic accuracy of median nerve distal motor latency, digit-wrist sensory latency, wrist-palm sensory conduction velocity, and wrist-palm/forearm sensory conduction velocity ratio (area under curve, 0.75-0.76). Median-ulnar digit-wrist sensory latency difference had a significantly higher diagnostic accuracy (area under curve, 0.80). Using the optimal cutoff value of 0.8 ms for abnormal sensory latency difference shown on the ROC curve the sensitivity was 70%, specificity 82%, positive predictive value 19% and negative predictive value 98%. Based on the clinical diagnosis among the symptomatic persons, the hand diagram (classified as classic/probable or possible/unlikely CTS) had high sensitivity but poor specificity. CONCLUSIONS: Using the clinical diagnosis of CTS as the criterion standard, nerve conduction tests had moderate sensitivity and specificity and a low positive predictive value in population-based CTS. Measurement of median-ulnar sensory latency difference had the highest diagnostic accuracy. The performance of nerve conduction tests in population-based CTS does not necessarily apply to their performance in clinical settings.

Adult↗

[The influence of conductive hearing loss on DPOAE-threshold. The effect of an individually optimized stimulation].

BACKGROUND: The DPOAE-threshold, estimated from extrapolated I/O functions, allows an objective assessment of the mechanical sensitivity of the inner ear. In children, the specificity of this diagnostic tool is impaired by conductive hearing loss. METHODS: In this study, we propose an individual optimization of the primary tone level ratio. This procedure allows the detection of a conductive hearing loss that can be accounted for when estimating the DPOAE-threshold. By means of a simulation using DPOAE-data from 22 normally hearing subjects, the effects of this procedure on the estimation of the DPOAE-threshold are examined. RESULTS: An individually optimized DPOAE stimulation distinctly improves the signal-to-noise ratio of the DPOAE which enables an estimation of the DPOAE-threshold for sound conductive losses up to 15 dB. The DPOAE-threshold only worsens in individual cases. CONCLUSIONS: An individually optimized stimulation paradigm may improve the specificity of inner ear diagnostics with the DPOAE-threshold. A clinical evaluation of the method in children, however, is necessary.

Acoustic Stimulation↗

Optimization of radiographic parameters for paediatric cardiac angiography.

In the paediatric cardiac catheterization laboratory the reduction of the radiation dose of diagnostic and interventional procedures is of high priority. Therefore, we performed an experimental study for optimizing the automatic exposure control (AEC) for cardiac angiography. With a Philips Integris BH 5000 system, six AEC programs were configured to acquire X-ray images of 8 cm to 18.5 cm thick PMMA phantoms at tube voltages between 50 kV and 90 kV, with 0.2 mm or 0.4 mm Cu filters and with or without an anti-scatter grid. At constant detector dose, entrance dose (ED) and image quality were evaluated as functions of the voltage. Changes in image quality were determined by the differential signal-to-noise ratio measured within regions of low (SNRb) and high (SNRd) attenuation. At equal voltages, ED saving was approximately 29% with the 0.4 mm Cu beam filtering as compared with 0.2 mm Cu, largely independent of object thickness. SNRb and SNRd were only dependent on the voltage. While SNRb was high at low voltages, SNRd showed a maximum at approximately 79 kV. Using a grid, ED increased with increasing object thickness by a factor of 1.9 to 3.5. At equal voltages, the grid led to significant image improvements, with SNRb and SNRd increasing by 27% and 11%, respectively. SNRb and SNRd are useful descriptors of the image quality in cardiac angiography. Highest image quality was found with tube voltages between 55 kV and 77 kV, independently of object thickness. To minimize dose, the thickness of the copper filter should be chosen to be as large as possible provided the tube's power limit allows keeping the voltage below the upper limit. In view of the substantial image improvement, the use of a grid is recommended for all patients, even for newborns.

Angiocardiography↗

[Potentialities of enhancing the diagnostic efficiency in registering the electrophoretic mobility of erythrocytes].

The potentialities of optimizing the clinical use of electric surface properties of erythrocyte blood samples were investigated. The ordinarily used parameter of the eletrokinetic erythrocyte potential based on the mean value of electrophoretic mobility was shown to be inaccurate and low informative. Asymmetry factor and erythrogram excess (distribution parameters) are recommended for use to enhance the adequate evaluation of changes in the above parameter and to make it diagnostically more effective. Principles of interpretation of changes' results are described.

Cell Movement↗

Image quality and dose in computed tomography.

Radiation exposure to the patient during CT is relatively high, and it is therefore important to optimize the dose so that it is as low as possible but still consistent with required diagnostic image quality. There is no established method for measuring diagnostic image quality; therefore, a set of image quality criteria which must be fulfilled for optimal image quality was defined for the retroperitoneal space and the mediastinum. The use of these criteria for assessment of image quality was tested based on 113 retroperitoneal and 68 mediastinal examinations performed in seven different CT units. All the criteria, except one, were found to be usable for measuring diagnostic image quality. The fulfillment of criteria was related to the radiation dose given in the different departments. By examination of the retroperitoneal space the effective dose varied between 5.1 and 20.0 mSv (milli Sievert), and there was a slight correlation between dose and high percent of "yes" score for the image quality criteria. For examination of the mediastinum the dose range was 4.4-26.5 mSv, and there was no significant increment of image quality at high doses. The great variation of dose at different CT units was due partly to differences regarding the examination procedure, especially the number of slices and the mAs (milli ampere second), but inherent dose variation between different scanners also played a part.

Humans↗

Comparison of the BACTEC MYCO/F Lytic bottle to the isolator tube, BACTEC Plus Aerobic F/bottle, and BACTEC Anaerobic Lytic/10 bottle and comparison of the BACTEC Plus Aerobic F/bottle to the Isolator tube for recovery of bacteria, mycobacteria, and fungi from blood.

The BACTEC MYCO/F Lytic blood culture bottle (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is designed to optimize the recovery of fungi and mycobacteria; however, this bottle also supports the growth of most aerobic bacteria. We compared the MYCO/F Lytic bottle with two other BACTEC bottles and the Isolator system for the recovery of bacteria as well as fungi and mycobacteria from blood. A total of 6,108 blood culture sets were inoculated with blood obtained from adult patients. Twenty-five to 28 ml of blood collected by a phlebotomy team for each blood culture set was randomly distributed into each of four blood culture receptacles: the Isolator tube (Wampole Laboratories, Cranbury, N.J.) and three BACTEC bottles: the MYCO/F Lytic bottle, the BACTEC Plus Aerobic/F bottle, and the BACTEC Anaerobic Lytic/10 bottle. The sediment from the Isolator tube was inoculated onto chocolate agar (CA), brain heart infusion agar (BHI), and Sabouraud dextrose agar (SDA) and into a BACTEC 13A bottle. Incubation durations were as follows: MYCO/F Lytic bottle, 42 days; Plus Aerobic/F bottle, 5 days; Anaerobic Lytic/10 bottle, 5 days; sediment from Isolator tube on CA, 3 days; sediment from Isolator tube on BHI, 30 days; sediment from Isolator tube on SDA, 30 days; and sediment from Isolator tube in a BACTEC 13A bottle, 42 days. Two isolates of Histoplasma capsulatum were recovered from the Isolator tube only. Three isolates of Mycobacterium tuberculosis complex were recovered: two isolates from the MYCO/F Lytic bottle only and one isolate from the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle) only. Two isolates of Cryptococcus neoformans were recovered: one from the MYCO/F Lytic bottle only and the other from the MYCO/F Lytic bottle and the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle). For potential pathogens overall, there was a statistical difference in recovery that favored the Isolator system over the MYCO/F Lytic bottle (P = 0.0015), including statistically significant differences for Staphylococcus aureus (P = 0.0001) and Streptococcus pneumoniae (P = 0.0313). However, there was no statistically significant difference between the two blood culture systems when detection of bloodstream infection was considered. The time to detection for all potential pathogens combined was less for the MYCO/F Lytic bottle than for the Isolator system (P = 0.0004). Overall, the potential pathogen recovery was greater for the BACTEC Plus Aerobic/F bottle than for either the Isolator system (P = 0.0003) or the MYCO/F Lytic bottle (P = 0.0001). However, the BACTEC Plus Aerobic/F bottle did not recover M. tuberculosis, H. capsulatum, or C. neoformans isolates. The combination of the Isolator system and MYCO/F Lytic bottle may be useful as a selective blood culture method to optimize the recovery of fungi and mycobacteria from blood. Compared with the manual Isolator system, the MYCO/F Lytic system has the advantage of less preanalytic processing and continuous automated monitoring of bottles for growth by the BACTEC 9240 instrument.

Adult↗

Non-microscopic method for malaria diagnosis using OptiMAL IT, a second-generation dipstick for malaria pLDH antigen detection.

Rapid diagnostic tests for malaria are now a commonly used procedure for malaria diagnosis. New or improved devices need to be evaluated against a recognised gold-standard procedure and subjected to conditions of temperature and humidity that may affect their performance. The OptiMAL 48 RDT has now been available commercially for several years and a second-generation OptiMAL IT test is now coming onto the market. In this study the problems associated with the routine use of OptiMAL 48 is investigated and its performance compared with a second-generation individual test, OptiMAL IT. Sensitivity and specificity for detection of all malaria species for both tests were comparable but loss of sensitivity of the test strips due to humidity or temperature found with the routine use of OptiMAL 48 was not seen with the individual OptiMAL IT. False-positive results for Plasmodium falciparum, seen in two negative blood samples, were attributed to the presence of high levels of heterophile antibodies.

Animals↗

The superiority of sequential over simultaneous testing.

Diagnostic tests are typically used to help the physician select among available management options. When two or more tests are available, using them sequentially is potentially more efficient than simultaneously performing multiple tests, in that the former approach may allow the physician to perform fewer tests. In particular, we demonstrate that if two common conditions are met, any simultaneous strategy involving at least as many tests as management options can be replaced by a sequential strategy with the same outcome and a smaller expected number of tests. It follows that, in many clinical situations in which the benefits of performing fewer tests outweigh the costs that may result from delaying diagnosis, simultaneous strategies cannot be optimal. This result can decrease the number of diagnostic strategies that the physician or decision analyst needs to consider.

Decision Making↗

[Screening for major dissociative disorders with the FDS, the German version of the Dissociative Experience Scale].

UNLABELLED: The prevalence of major dissociative disorders (dissociative identity disorder, DID and similar forms of dissociative disorder not otherwise specified, DDNOS) in clinical samples is about 5 %. Despite their frequency, major dissociative disorders are often overseen for a long time. Screening-scales have proved to be effective to support clinical diagnosis. The aim of this study was to test, whether the Fragebogen für dissoziative Symptome (FDS), the German version of the Dissociative Experiences Scale (DES), differentiates between patients with dissociative disorders, non-dissociative disorders and non-clinical controls. Additionally, an optimal FDS-cutoff for a more detailed differential-diagnostic evaluation of the dissociative symptomatology should be identified. 150 participants with DID (group DID: n = 44), DDNOS (DDNOS: n = 22), posttraumatic disorders (TRAUMA: n = 20), other non-dissociative disorders (non-TRAUMA: n = 34) and non-clinical controls (KG: n = 30) completed the FDS. In the five diagnostic groups, mean values were calculated and compared for the FDS, DES and FDS-20. Via receiver-operating-curves the cutoff-scores, which differentiated best between participants with and without major dissociative disorders, were identified. FDS, DES and FDS-20 differentiate significantly between patients with and without major dissociative disorders. For all scales, there were significant differences between the diagnostic groups, with mean-scores decreasing continuously from the groups DID to DDNOS and TRAUMA. Between the groups non-TRAUMA and KG tendencies were found in the predicted direction. The optimal cutoff-scores to differentiate between participants with and without major dissociative disorders were 13 (FDS/FDS-20) and 15 (DES). Using these cutoff-scores, at least 90 % of the patients with major dissociative disorders could be identified correctly (sensitivity). The specifity of the scales was 0.89 to 0.90. CONCLUSION: Screening for major dissociative disorders with the FDS, DES and FDS-20 allows to identify patients with or without major dissociative disorders correctly in about 90 % of the cases. Therefore, the FDS should be used routinely in psychiatric and psychotherapeutic clinics and practices to identify high risk patients. Such a procedure would be an important step towards an improvement of the diagnostic and therapeutic care of patients with major dissociative disorders, which is still often unsatisfactory at present.

Adolescent↗