Biomedical subjects

M Hoppe

Publications and source records attributed to M Hoppe.

At least 19 recordsLinked to original sources

PubMed2006

Aminoterminal B-type pro-natriuretic peptide as a marker of recovery after high-risk coronary artery bypass grafting in patients with ischemic heart disease and severe impaired left ventricular function.

BACKGROUND: Aminoterminal B-type pro-natriuretic peptide (NT-proBNP) is a reliable indicator of heart failure severity. Levels of NT-proBNP are markedly increased in patients with coronary artery disease (CAD) and severely impaired left ventricular (LV) function. The aim of our study was to assess the impact of NT-proBNP levels after high-risk coronary artery bypass grafting (CABG) with regard to recovery potential. METHODS: Between 1998 and 2004, 121 patients with CAD and severely impaired LV function, who were undergoing CABG, were investigated. Their mean age was 64 +/- 11 years. All patients were in New York Heart Association (NYHA) Class III/IV status; LV ejection fraction (EF) was 20 +/- 6%. All survivors underwent follow-up (59 +/- 34 months) spiroergometric, electrocardiographic (ECG) and echocardiographic assessment and were tested for routine blood controls and NT-proBNP levels (Roche, Mannheim, Germany). RESULTS: The survival rate after 8 years was 70%. All survivors received follow-up assessment. Among survivors the median NT-proBNP level at follow-up was 896 (521 to 1,687) pg/ml. The maximum oxygen uptake was 14.6 +/- 4.9 ml/min/kg, and EF increased to 42% at follow-up among all survivors. On dichotomizing survivors into two groups with NT-proBNP levels above and below the median, the post-operative body mass index was significantly higher in the high NT-proBNP group (p = 0.036). EF (p = 0.028) and NYHA classification (p < 0.05) improved significantly in both groups, with a tendency toward higher EF in the low NT-proBNP group. CONCLUSIONS: Patients undergoing a high-risk CABG procedure have a survival rate comparable to heart transplantation patients and show a potential for clinical and myocardial recovery. NT-proBNP use a useful marker for recovery after a high-risk CABG procedure, with significant correlation with clinical parameters.

Aged↗

PubMed2005

Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome.

Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the type of epilepsy most frequently operated on. The predictors for long-term seizure freedom after surgery of TLE-HS are unknown. In this study, we aimed to identify prognostic factors which predict the outcome 6 months and 2, 3 and 5 years after epilepsy surgery of TLE-HS. Our working hypothesis was that the prognostic value of potential predictors depended on the post-operative time interval for which the assessment was made. We included 171 patients (100 females and 71 males, aged 16-59 years) who had undergone presurgical evaluation, including video-EEG, who had had MRI-defined HS, and who had undergone temporal lobectomy. We found that secondarily generalized seizures (SGTCS) and ictal dystonia were associated with a worse 2-year outcome. Both these variables together with older age and longer epilepsy duration were also related to a worse 3-year outcome. Ictal limb dystonia, older age and longer epilepsy duration were associated with long-term surgical failure evaluated 5 years post-operatively. In order to determine the independent predictors of outcomes, we calculated multivariate analyses. The presence of SGTCS and ictal dystonia independently predicted the 2-year outcome. Longer epilepsy duration and ictal dystonia predicted the 3-year outcome. Longer epilepsy duration (P = 0.003) predicted a poor 5-year outcome. Conclusively, predictors for the long-term surgical results of TLE with HS are different from those variables that predict the short-term outcome. Epilepsy duration is the most important predictor for long-term surgical outcome. Our results strongly suggest that surgery for TLE-HS should be performed as early as possible.

Adolescent↗

PubMed2005

Vagus nerve stimulation: predictors of seizure freedom.

OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS implantation at one centre and had at least one year of follow up were studied. They underwent complete presurgical evaluation including detailed clinical history, magnetic resonance imaging, and long term video-EEG with ictal and interictal recordings. After implantation, adjustment of stimulation parameters and concomitant antiepileptic drugs were at the discretion of the treating physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7 to 53). Six patients (13%) became seizure-free after the VNS implantation. Only two variables showed a significant association with the seizure-free outcome: absence of bilateral interictal epileptiform discharges (IED) and presence of malformation of cortical development (MCD). Epilepsy duration showed a non-significant trend towards a negative association with outcome. By logistic regression analysis, only absence of bilateral IED correlated independently with successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4 to 353)). Bilateral IED (independent or bilateral synchronous) was found in one of six seizure-free patients and in 33 of 41 non-seizure-free patients. When bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83 (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS: Bilateral IED was independently associated with the outcome of VNS. These results are preliminary because they were based on a small patient population. They may facilitate prospective VNS studies enrolling larger numbers of patients to confirm the results.

Adolescent↗

PubMed2005

Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy.

OBJECTIVES: We wanted to investigate factors that are associated with frequency of interictal epileptiform discharges by investigating 303 patients with temporal lobe epilepsy (TLE). METHODS: We included all patients who consecutively underwent the adult presurgical evaluation program at our center and who had intractable, medial TLE with complex partial seizures due to unilateral medial temporal lobe lesions. The interictal EEG samples were automatically recorded and stored on computer. The location and frequency of interictal epileptiform discharges were assessed by visual analysis of interictal EEG samples of 2-minute duration every hour. RESULTS: There were 303 patients (aged 16-63) who met the inclusion criteria. The median interictal epileptiform discharge frequency was 15 IED/h, the median seizure frequency was 4 seizures/month. According to univariate analyses, we found that age at monitoring, epilepsy duration, and higher seizure frequency were associated with higher interictal epileptiform discharge frequency. In the logistic regression analysis, we found that higher seizure frequency (p < 0.001) and longer epilepsy duration (p = 0.007) were independently associated with higher spike frequency, while the age at monitoring was not. CONCLUSIONS: Seizure frequency and epilepsy duration (years of patient's life with seizure activity) were independently associated with IED frequency, suggesting that IED are modulated by seizures.

Adolescent↗

PubMed2004

Intentional seizure interruption may decrease the seizure frequency in drug-resistant temporal lobe epilepsy.

We investigated the nature of preictal subjective phenomena and whether they had any effect on the seizure frequency in 95 adult patients with medial temporal lobe epilepsy. Seventy-three (77%) patients indicated that they experienced seizure-provoking factors. Ten patients (11%) had prodromas independent of auras, while auras occurred in 89%. Forty-four patients (46%) reported that that they had tried to stop their seizures in the presence of prodroma or aura and this action had resulted in success at least once. Twenty-one patients (22%) regularly tried to stop their seizures because this effort was often successful according to their interpretation. Patients who reported that they could frequently inhibit their seizures had 1.8 +/- 1.6 seizures/month, a significantly lower mean seizure frequency than those 74 patients who did not do it regularly (4.6 +/- 4.8 seizures/month, P<0.001). Patients who reported regular experience in inhibiting intentionally their seizures more often had affective (P=0.05) and vertiginous auras (P<0.01) as well as isolated auras (P<0.05). Patients who experienced provoking factors showed the same seizure frequency as those who did not. Our results suggest that intentional seizure inhibition had an impact on the severity of drug-resistant epilepsy.

Adolescent↗

PubMed2004

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry.

OBJECTIVE: Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. MATERIAL AND METHODS: Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. RESULTS: Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). CONCLUSION: Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome.

Action Potentials↗

PubMed2004

Tetrodotoxin-induced conduction blockade is prolonged by hyaluronic acid with and without bupivacaine.

BACKGROUND: In isolated nerves, tetrodotoxin (TTX) blocks nerve conduction longer than bupivacaine. In vivo, however, both substances block nerve conduction to an equal duration, presumably because the hydrophilic TTX binds only weakly to the perineural tissue. High molecular weight hyaluronic acid (HA) prolongs the action of local anaesthetics several-fold. We tested whether admixture of HA enhances the binding of TTX to the perineural tissue and thus induces an ultra-long conduction block after a single application. METHODS: In 12 anaesthetized rabbits, the minimal blocking concentrations of TTX, TTX and HA (TTX/HA) and bupivacaine with HA (bupivacaine/HA) were determined by blocking the natural spike activity of the aortic nerve. In 18 other animals, equipotent concentrations of either TTX, TTX/HA or TTX/bupivacaine/HA were applied topically to the aortic nerve. After disappearance of the spike activity, the wound was closed to simulate the clinical situation of a single shot nerve block. The time until recovery of spike activity was determined. The nerves were examined for signs of neurotoxicity 24 h after the application of the drugs. Data are presented as means +/- SD and compared by ANOVA and Student's t-test for unpaired data. RESULTS: The conduction block by TTX/bupivacaine/HA (10.1 +/- 1.9 h) or TTX/HA (9.3 +/- 1.0 h) was significantly longer than that of plain TTX (7.9 +/- 1.0 h). Neurotoxicity was not observed. CONCLUSIONS: Both HA and HA/bupivacaine prolong the TTX-induced conduction blockade of the aortic nerve of rabbits in vivo. No signs of neurotoxicity were observed.

Anesthetics, Local↗

PubMed2004

Tetrodotoxin-induced conduction blockade is prolonged by hyaluronic acid with and without bupivacaine.

Anesthetics, Local↗

PubMed2003

Spikes on the postoperative EEG are related to preoperative spike frequency and postoperative seizures.

PURPOSE: To investigate the factors which influence the persistence of interictal epileptiform discharges (IED) after epilepsy surgery. METHODS: In this retrospective study we included patients with intractable medial temporal lobe epilepsy (MTLE) who underwent presurgical evaluation including high-resolution MRI and video-EEG monitoring with seizure registration prior to an anterior temporal lobe resection. The postsurgical outcome was assessed by our team 6 months and 2 years after the surgery. RESULTS: One hundred and forty-seven patients fulfilled the inclusion criteria. The mean age of the patients was 31.8 (range 16-59 years). In 22 patients (15%) interictal epileptiform discharges were present on the postoperative routine EEG. We found that both the preoperative spike frequency ( P < 0.001 ) and postoperative seizures ( P = 0.04 ) were independently associated with the presence of IED on the postoperative routine EEG. The preoperative spike frequency was not associated with the postoperative outcome. The extent of resection showed no influence on the presence of postoperative IED. CONCLUSION: We hypothesize that two factors independently influence the presence of postoperative spikes: chronic interictal disturbance (represented as preoperative spike frequency) and the acute (postoperative) seizures. Our study confirmed that persistent postoperative IED had a prognostic value regarding the outcome of the epilepsy surgery.

Action Potentials↗

PubMed2003

Clinical differences in patients with unilateral hippocampal sclerosis and unitemporal or bitemporal epileptiform discharges.

PURPOSE: To investigate factors determining the presence of bilateral interictal epileptiform discharges (IEDs) in temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS). METHODS: We analysed data of 243 TLE patients with unilateral HS who had long-term video-EEG. Eighty-one patients (33%) had bitemporal IEDs. RESULTS: We categorised patients into a unilateral group (UG), a bilateral group (BG) according to presence of bitemporal IEDs. We found no difference between UG and BG regarding epilepsy duration, secondarily generalised seizures, and history of febrile seizures. Mean seizure frequency was significantly higher in the BG (UG: 7.7+/-14.7 seizures/month; BG: 13+/-35 seizures/month, P=0.01). We found a significant correlation between late epilepsy onset and the presence of bitemporal IEDs. The mean age at epilepsy onset in UG was 10.1+/-7.9 years, while in BG it was 13+/-9.2 years (P=0.02). CONCLUSIONS: The traditional concept of the evolution of mirror focus cannot apply for humans because the duration of epilepsy does not influence the evolution of bitemporal IEDs. Other factors, i.e. age at onset and seizure frequency may play a role in this process. The association between the higher seizure frequency and mirror foci indicates that the development of mirror focus depends on seizures and not on a progressive 'interictal' epileptogenesis.

Adolescent↗

PubMed2003

Serum iron concentration as a tool to measure relative iron absorption from elemental iron powders in man.

OBJECTIVE: To present a new method for measuring the relative bioavailability (RBV) of commercial elemental iron powders by investigating induced changes of serum iron concentration (S-Fe) in relation to ferrous sulphate (FeSO4). Earlier studies have shown that in a group of subjects there is good agreement between the increase in S-Fe and the amount of iron absorbed from a simple iron salt as FeSO4. METHODS: The study included two groups of male blood donors (n=2 x 16 subjects) who were served three meals with an interval of approximately nine weeks between each one. In one group the meal was fortified with reduced iron, ferrous sulphate or no iron at all. In the other group the meal was fortified with electrolytic iron, ferrous sulphate or no iron. The S-Fe increase was followed for 6 h. Studying the non-iron meals was necessary so that the basal diurnal variation in the S-Fe during the six hours could be measured and subtracted. RESULTS: The mean S-Fe increase calculated as the area under the curve (AUC) from the reduced iron (RBV=0.43) and the electrolytic iron (RBV=0.73) differed significantly from the AUC following FeSO4 (p=0.002 and p=0.021, respectively). The difference between the reduced and the electrolytic iron was also statistically significant (p=0.036). CONCLUSION: Measuring increases in S-Fe could be a reliable and simple method to determine the RBV in comparative studies of elemental iron powders in relation to FeSO4.

Adult↗

PubMed2002

Does the application of gadolinium-DTPA have an impact on magnetic resonance phase contrast velocity measurements? Results from an in vitro study.

INTRODUCTION/OBJECTIVE: To evaluate the potential influence of various concentrations of gadolinium (Gd)-DTPA on magnetic resonance phase contrast (MR PC) velocimetry. MATERIAL AND METHODS: Imaging was done with a 1.0 T scanner using a standard Flash 2D sequence and a circular polarized extremity coil. In a validated flow phantom with a defined 75% area stenosis different concentrations of Gd-DTPA, diluted in a 10:1 water-yogurt mixture, MR PC measurements were correlated with a Doppler guide wire as gold standard. RESULTS: MR PC measurements correlated well with the Doppler derived data (r=0.99; P<0.01; maximum pre-stenotic velocity: 21.6+/-0.5 cm/s; maximum intra-stenotic velocity: 81.7+/-0.6 cm/s). Following Gd-DTPA administration no significant (P>0.05; Student's t-test) flow measurement changes were noted (maximum pre-stenotic velocity: 21.3+/-1.3 cm/s; maximum intra-stenotic velocity: 84.0+/-3.6 cm/s). However, delineation of the perfused lumen was enhanced after the application of Gd-DTPA. DISCUSSIONS AND CONCLUSION: The application of Gd-DTPA does not affect MR PC velocimetry. However, the application of contrast media allowed a more accurate vessel segmentation. MR PC measurements can be reliably carried out after application of Gd-DTPA.

Blood Flow Velocity↗

PubMed2002

Magnetic resonance phase contrast velocity measurement for non-invasive follow up after percutaneous transluminal angioplasty.

BACKGROUND: The aim of this study was to evaluate magnetic resonance phase contrast velocimetry (MRVL) as a non-invasive follow up tool to assess restenosis after percutaneous transluminal angioplasty (PTA). PATIENTS AND METHODS: We prospectively investigated 51 consecutive patients who underwent PTA of the femoropopliteal region. MRVL was conducted prior, one day, six weeks, twelve weeks and 24 weeks after PTA using a circular polarized extremity coil and a gradient echo sequence (TR/TE 600/6 ms, flip angel 30 degrees, slice thickness 10 mm). Hemodynamic data, derived from the MR phase contrast sequence, allowed to calculate the degree of area stenosis of the lesion treated with PTA. These data were correlated with clinical hemodynamic parameters (ankle-brachial index and walking distance). RESULTS: The mean grade of area stenosis was 69% +/- 27% before PTA, 30% +/- 20% one day, 29% +/- 23% six weeks, 39% +/- 17% twelve weeks and 42% +/- 18% 24 weeks after PTA and correlated well with clinical data and the post angioplasty clinical course of the patients. CONCLUSIONS: Follow up measurements using MRVL are suitable to assess restenosis after PTA and allow quantifying the grade of recurrent stenosis as well as the hemodynamic consequences.

Aged↗

PubMed2001

Lack of aura experience correlates with bitemporal dysfunction in mesial temporal lobe epilepsy.

UNLABELLED: The diagnostic value of lack of aura experience in patients with temporal lobe epilepsy (TLE) is unclear. PURPOSE: To evaluate possible factors of bitemporal dysfunction in patients with mesial TLE who did not experience an aura in electroencephalography EEG/video monitoring for epilepsy surgery. METHODS: Ictal scalp EEG propagation patterns of 347 seizures of 58 patients with mesial temporal lobe sclerosis or non-lesional mesial TLE, interictal epileptiform discharges (IED), presence of unilateral mesial temporal lobe sclerosis in visual magnetic resonance imaging (MRI) analysis, prose memory performance, history or not of an aura, and postictal memory or absence of an aura were analyzed. The ictal EEG was categorized as follows. EEG seizure: (a) remaining regionalized, (b) non-lateralized, (c) showing later switch of lateralization or bitemporal asynchronous ictal patterns. RESULTS: Absent aura in monitoring was significantly correlated with absence of unitemporal MRI sclerosis (P=0.004), bitemporal IED (P=0.008), and propagation of the ictal EEG to the contralateral temporal lobe (P=0.001). Other historical data and interictal prose memory performance were not significantly correlated with absent aura. Ten of 11 patients without aura in monitoring also had absent or rare auras in their history. CONCLUSIONS: Lack of aura experience strongly correlates with indicators of bitemporal dysfunction such as bitemporal interictal sharp waves and bitemporal ictal propagation in scalp EEG, and absence of lateralized MRI sclerosis in patients with mesial TLE. The fact that absent auras are not correlated with episodic memory suggests a transient memory deficit, probably because of rapid propagation to the contralateral mesial temporal lobe.

Adolescent↗

PubMed2001

Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy.

PURPOSE: To analyze the spatio-temporal relationship between seizure propagation and interictal epileptiform discharges (IEDs) in patients with bitemporal epilepsy. METHODS: We investigated 18 adult patients with intractable temporal lobe epilepsy (TLE) who had undergone continuous video-EEG monitoring during presurgical evaluation. Only those patients were selected who had independent IEDs over both temporal lobes. Two authors evaluated the ictal and interictal EEG data independently. RESULTS: We analyzed 52 lateralized seizures of 18 patients. Thirty-one seizures showed ipsilateral seizure spread exclusively, whereas in 21 seizures the contralateral hemisphere was also involved. In lateralized seizures without contralateral propagation, we found that spikes ipsilateral to the seizure onset occurred postictally in a greater ratio than preictally (P<0.001). In lateralized seizures with contralateral propagation, we found no significant changes in the postictal spike distribution. CONCLUSIONS: Our findings showed that the lateralization of IEDs may depend on the brain areas involved by the preceding seizures, suggesting that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity.

Electroencephalography↗

PubMed2001

Prospective comparison of MR phase-contrast velocimetry with intravascular doppler US during infrainguinal artery angioplasty.

PURPOSE: To evaluate the accuracy of magnetic resonance (MR) velocimetry for quantitative assessment of stenosis in patients undergoing percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: Thirty patients underwent PTA of the infrainguinal region. To assess hemodynamic parameters of lesions, MR phase-contrast velocimetry with a circular-polarized extremity receiver coil and a cardiac gated gradient echo sequence was conducted before and 1 day after PTA. Additionally, all lesions were examined by means of intravascular Doppler flow measurements (0.018-inch wire, 12 MHz). From these data, the degree of stenosis was calculated and a comparison of MR velocimetry with intravascular Doppler US was undertaken. RESULTS: Correlation between calculated grade of stenosis for MR velocimetry and intravascular Doppler US was good and significant (r = 0.74; P <.001). Calculated luminal stenosis grade were similar for both methods before PTA (intravascular Doppler US: 0.62 +/- 0.18, MR velocimetry: 0.54 +/- 0.19; P =.17 with paired Student t-test) and after PTA (0.25 +/- 0.23 and 0.3 +/- 0.2, respectively; P =.56). CONCLUSION: MR velocimetry results in reliable noninvasive in vivo flow measurements and allows accurate assessment of stenosis in a clinical setting.

Aged↗

PubMed2001

Differences by gender and sexual experience in adolescent sexual behavior: implications for education and HIV prevention.

Researchers examined individual characteristics and peer influences related to adolescents' sexual behavior, taking gender and sexual experience into account. As part of a larger, longitudinal study investigating youth health awareness, 8th, 9th, and 10th graders reported their intentions to engage in sexual activity and use condoms in the next year, the amount of pressure they felt to engage in sexual activity, and their perceptions about the number of their peers engaging in sexual activity. Findings suggest intentions to engage in sexual behavior and use condoms, feelings of pressure to have sex, and perceptions about the number of friends engaging in sexual intercourse differ by gender and sexual experience status. Implications of these findings for health and sexuality education, as well as HIV prevention programs targeted at adolescents, are discussed.

Adolescent↗

PubMed2001

Transient lesion in the splenium of the corpus callosum: three further cases in epileptic patients and a pathophysiological hypothesis.

OBJECTIVE: Focal lesions limited to the splenium of the corpus callosum (SCC) are rare and little is known about their aetiology. Three patients were examined for presurgical evaluation in epilepsy with a transient lesion in the SCC and a pathophysiological hypothesis is presented. METHODS: Three patients were identified with a circumscribed lesion in the centre of the corpus callosum. Follow up MRI was performed, the medical records examined retrospectively, and the literature reviewed. RESULTS: The patients showed identical lesions in the SCC with reduced T1 and increased T2 signal intensity and an unaffected marginal hemline of a few mm. Patients were asymptomatic and control MRIs showed complete normalisation within 2 months. Patients had been treated with antiepileptic drugs (AEDs) without signs of toxicity. In all patients AEDs were rapidly reduced for diagnostic purposes, but only one had psychomotor seizures, 5 days before imaging. CONCLUSIONS: A transient lesion in the SCC has so far only been described in 13 patients with epilepsy and has been interpreted either as reversible demyelination due to AED toxicity or transient oedema after secondary generalised seizures. The data confirm neither of these hypotheses. A transient lesion in the SCC seems to be a non-specific end point of different disease processes leading to a vasogenic oedema. This suggests, in these patients, a multifactorial pathology triggered by transient effects of AEDs on arginine vasopressin and its function in fluid balance systems in a condition of vitamin deficiency. The complete and rapid reversibility in all cases without specific intervention is emphasised and any invasive diagnostic or therapeutic approach is discouraged.

Adult↗