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Neurocognitive correlates of therapeutic alliance in schizophrenia.

Although therapeutic alliance in schizophrenia has been linked with treatment adherence and outcome, less is known about its clinical correlates. This study explored neurocognition as a possible predictor of perceived therapeutic alliance among people with schizophrenia in cognitive behavior therapy. Twenty-four participants with schizophrenia spectrum disorders and their therapists were administered the Working Alliance Inventory, Short Form after 3 months of therapy. Totals for clients and therapists were correlated with measures of verbal memory, premorbid intelligence, visual spatial reasoning, executive function, and attention, all obtained before beginning therapy. Poorer performance on verbal memory was significantly related to client report of stronger alliance, whereas better performance on visual spatial reasoning was significantly related to therapist report of stronger alliance. Client and therapist ratings of therapeutic alliance were significantly and positively related. Clients' abilities may differentially affect therapist and client perception of therapeutic alliance in schizophrenia.

Attitude of Health Personnel↗

Human endotoxemia: a model for mechanistic insight and therapeutic targeting.

The diversity of phenotypic manifestations, comorbidities, and therapeutic algorithms in patients with severe inflammation have confounded efforts to translate mechanistic insights from the bench top to the bedside. This dilemma has negatively impacted upon many therapeutic interventions that exhibited seemingly well-reasoned preclinical portfolios. Prudence urges the assessment of potent immunoregulatory therapies, wherever possible, in models that replicate the clinical phenotype absent overt manifestations of genetically or environmentally modified processes. The healthy human model of endotoxin administration (systemic or endobronchial) provides such an opportunity and has been used to great advantage for gaining insight into mechanisms of disease and for determination of therapeutic signal strength. When thoughtfully interpreted, the model may provide proof of principle as well as lessen the unpredictability of clinical responses. Although the broad characteristics of this model are well described in the literature, it is recognized that this model does not fully replicate the magnitude of initial inflammatory stress nor the latent spectrum of inflammation/sepsis-inducible organ system pathologies. Nevertheless, the similarities between the early, transient clinical phenotype, inducible physiochemical change, and biochemical pathway activation of this model to the early hyperdynamic phase of resuscitated injury and infection are striking. Rational testing of a therapeutic mechanism requires a quantifiable and reproducibly altered marker of the hypothetical mechanism. Given the modest nature of endotoxin induced insult, interventions that demonstrate target specific efficacy in conjunction with attenuated phenotype responses are more likely to exhibit efficacy within lower risk patient populations. By contrast, the model cannot predict clinical efficacy among higher risk patients nor in those who have endured extended periods of inflammatory stress.

Endotoxemia↗

Exploring the therapeutic targets and signaling mechanisms of quercetin activity against radiation skin ulcer based on the observational research of network pharmacology.

Radiation skin ulcer is a common adverse complication after radiotherapy. Currently, there is no efficient therapy for this complication. In this study, we searched for the potential pathological targets of radiation skin ulcer and the potential pharmacological targets of quercetin, respectively, and obtained the potential therapeutic targets after intersection. Subsequently, an array of bioinformatics assessments on possible therapeutic targets was conducted, encompassing functional enrichment studies, analysis of protein interaction networks, identification of key targets, and validation through molecular docking. The enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways shows that the therapeutic effect of quercetin on radiation skin ulcer may be through targeting aging cells. In addition, we identified 5 core targets, including AKT1, EGFR, MAPK3, SRC, and TP53. They are significantly enriched in EGFR tyrosine kinase inhibitors (SRC, AKT1, EGFR, and MAPK3) and epidermal growth factor receptor signaling pathways (SRC, EGFR, and AKT1), indicating the importance of EGFR signaling. Quercetin may have a therapeutic effect on radiation skin ulcer by targeting aging cells. Specifically, it may act through 4 core targets, including AKT1, EGFR, SRC, and TP53.

Quercetin↗

Small-molecule therapeutics for the treatment of glycolipid lysosomal storage disorders.

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease-related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed 'substrate deprivation' or 'substrate reduction therapy' (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N-alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide-specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N-alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro, in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

Animals↗

The therapeutic window after spinal cord injury can accommodate T cell-based vaccination and methylprednisolone in rats.

Immune system activity has traditionally been considered harmful for recovery after spinal cord injury (SCI). Recent evidence suggests, however, that immune activity--and specifically autoimmune activity--is evoked by the insult, is beneficial if properly regulated and is amenable to boosting. Thus, for example, vaccination with an altered peptide ligand derived from myelin basic protein reduces the progressive degeneration of neurons that escaped the initial insult, thereby promoting recovery after SCI. As the steroid drug methylprednisolone (MP) is currently the only treatment available for patients with SCI, our purpose in the present study was to examine the mutual compatibility of the two treatments within the post-traumatic therapeutic window. We show, using rats of two different strains, that if MP is injected concomitantly with the therapeutic vaccination, the beneficial effect of the vaccination is diminished. However, if MP is given immediately after the insult and the vaccination 48 h later, MP does not detract from the beneficial effect of the vaccination. These results demonstrate that the therapeutic window after SCI can accommodate immediate administration of MP plus a delayed therapeutic vaccination.

Analysis of Variance↗

The role of the therapeutic alliance in the treatment of substance misuse: a critical review of the literature.

BACKGROUND: In the past two decades, a number of studies investigating the role of the therapeutic alliance in drug treatment have been published and it is timely that their findings are brought together in a comprehensive review. AIMS: This paper has two principal aims: (1) to assess the degree to which the relationship between drug user and counsellor predicts treatment outcome and (2) to examine critically the evidence on determinants of the quality of the alliance. METHODS: Peer-reviewed research located through the literature databases Medline, PsycInfo and Ovid Full Text Mental Health Journals using predefined search-terms and published in the past 20 years is considered. Further papers were identified from the bibliographies of relevant publications. FINDINGS: A key finding is that the early therapeutic alliance appears to be a consistent predictor of engagement and retention in drug treatment. With regard to other treatment outcomes, the early alliance appears to influence early improvements during treatment, but it is an inconsistent predictor of post-treatment outcomes. There is relatively little research on the determinants of the alliance. In studies that are available, clients' demographic or diagnostic pre-treatment characteristics did not appear to predict the therapeutic alliance, whereas modest but consistent relationships were reported for motivation, treatment readiness and positive previous treatment experiences. CONCLUSIONS: The therapeutic alliance plays an important role in predicting drug treatment process outcomes, but too little is known about what determines the quality of the relationship between drug users and counsellors.

Humans↗

The anti-CD20 antibody rituximab augments the immunospecific therapeutic effectiveness of an anti-CD19 immunotoxin directed against human B-cell lymphoma.

The chimaeric anti-CD20 antibody rituximab (Rituxan) sensitises lymphoma cells to small molecule cytotoxic drugs and to protein toxins. We have explored the augmentive effect of rituximab on the anti-CD19 immunotoxin BU12-SAPORIN in a model of human lymphoma. Intact rituximab and its F(ab)2 derivative both augmented the immunospecific protein synthesis inhibitory effects of BU12-SAPORIN in a complement-independent manner. A combination of rituximab + BU12-SAPORIN completely abolished the proliferation of Ramos cells in vitro and also induced a significantly greater degree of apoptosis in these cells. Treatment with rituximab, BU12-SAPORIN or a combination of both induced poly(ADPribose) polymerase and caspase 3 cleavage, although this was always consistently greater in combination-treated cells. zVAD almost completely inhibited apoptosis in rituximab- or BU12-SAPORIN-treated cells but only partially in combination-treated cells. In severe combined immunodeficient (SCID)-Ramos mice the combination of rituximab + BU12-SAPORIN was significantly better therapeutically than either single agent. The immunological fidelity of the therapeutic effect because of combination treatment was demonstrated through the failure of rituximab to augment an irrelevant anti-CD7 immunotoxin. The therapeutic efficacy of rituximab and combination treatment was reduced in SCID-Ramos mice depleted of serum complement while natural killer cell depletion failed to show any convincing role for antibody-dependent cellular cytotoxicity. This study shows a clear therapeutic advantage from using rituximab to immunospecifically augment immunotoxin cytotoxicity warranting further investigation.

Animals↗

An audit of therapeutic drug monitoring procedures--use of theophylline assay services.

Monitoring therapy involving drugs exhibiting high intersubject variation and/or narrow therapeutic index has become more generally accepted in hospitals. This paper describes an audit conducted jointly by clinical pharmacists and clinical biochemists into the use and therapeutic value of a drug monitoring service in a general hospital using theophylline as a model. Assay values were categorized as 'subtherapeutic', 'therapeutic' or 'potentially toxic'. The reporting procedures involving the two departments were evaluated along with action taken by the requesting clinicians. The study showed that 60% of the theophylline assay results fell within the therapeutic range at the time of sampling. However only 38% of samples were considered to have been taken under steady state conditions. There was a significant delay in relaying the results to the clinicians. Procedural changes involving sampling times, analytical techniques, recording and conveying results to clinicians and co-operative policies between the departments of pharmacy and clinical chemistry have been implemented as a result of this study.

Adult↗

Functional assessment of therapeutic anti-D immunoglobulin using Fc-mediated assays.

Therapeutic anti-D immunoglobulin preparations issued by the Scottish National Blood Transfusion Service, between 1980 and 1986, were evaluated using in-vitro Fc-mediated functional tests that reflect potential in-vivo mechanisms of specific red cell destruction and clearance. All batches tested were found to: (a) contain anti-D of mainly IgG1 subclass and lesser amounts of IgG3; (b) mediate lymphocyte and monocyte rosetting; and (c) produce lytic activity in both K cell and monocyte ADCC. The functional activity of the therapeutic immunoglobulin preparations over this period of production had not altered despite increased plasma contributions latterly to the pool from deliberately immunized male donors. This is the first in-vitro study of the Fc-mediated function of therapeutic polyclonal anti-D preparations. As these preparations were clinically effective in the prophylactic anti-D programme, such bioassays of FcRI/II and FcRIII activity are justified for the future evaluation of immune plasma before blending for fractionation and production of therapeutic anti-D immunoglobulin.

Antibody-Dependent Cell Cytotoxicity↗

[Therapeutic itinerary of poor patients in Benin (poverty and health care)].

OBJECTIVE: There is great risk of excluding the poor in a system where patients are charged for medical care. Our objective was to identify the stages of the therapeutic itinerary of poor and nonpoor patients in case of illness. METHOD: Prospective study over 12 months, in 16 sites selected randomly after dividing the territory of Benin into four strata. The sample included 1312 households (668 poor and 644 nonpoor) and 9554 people. Those who were ill during the study period were interviewed on the therapeutic itinerary chosen. RESULTS: A total of 1959 (20.5%, of whom 1091 were poor) of the 9554 people in our sample experienced at least one episode of illness. The nonpoor chose the health centres in the first instance more frequently than the poor (26.3%vs. 20%; P < 0.001); but the first choice of most patients (66.4% of poor and 63.9% of the nonpoor patients) was modern or traditional self-medication. Within the strata (regions), indigents and nonpoor in the urban region and the north chose different treatments in the first instance (P < 0.001). Apart from the first treatment chosen, no significant difference was observed between the therapeutic satisfaction of both groups. Patients unsatisfied with the first step of treatment were essentially those who used traditional or modern self-medication. Despite this, modern and traditional self-medication remain the most frequent second step choice for both poor and nonpoor patients. CONCLUSION: The main difference between poor and nonpoor people's therapeutic itinerary is that nonpoor people more often use state health facilities first than the poor.

Benin↗

How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis.

BACKGROUND: It is difficult to demonstrate Mycobacterium tuberculosis in smears or biopsies and to grow it in culture in cutaneous tuberculosis because most cases are paucibacillary. A therapeutic trial of antitubercular drugs is frequently used to confirm the diagnosis in difficult cases. Information is lacking on the response to antitubercular therapy in cutaneous tuberculosis; consequently there are no clear guidelines on when to expect a response and also when to abandon a therapeutic trial. METHODS: We studied the records of 60 patients treated for cutaneous tuberculosis at our hospital to study the time course of the therapeutic response. All patients were treated with a short-course antitubercular regimen consisting of isoniazid 300 mg daily, rifampicin 450 mg daily, ethambutol 800 mg daily and pyrazinamide 1500 mg daily for 2 months followed by isoniazid and rifampicin in the same doses for 4 months. At follow-up visits, each patient was assessed by a dermatologist who recorded the presence or absence of clinical improvement in the skin lesions. RESULTS: Of the 60 patients seen, eight patients did not follow up after the initial consultation, 48 patients improved with treatment and four patients were classified as treatment failures. The timing of the first visit varied from 3 days to 15 months (median 27.5 days, mean 58.96 +/- 94.50) after initiation of treatment. Twenty-one patients were recorded to have improved within the first month of therapy. Twenty-seven patients who first reported more than 30 days after initiation of treatment were found to have improved. Four patients failed to respond during follow up ranging from 3 to 17 months. CONCLUSION: When a therapeutic trial is undertaken in cutaneous tuberculosis, 6 weeks of therapy with four drugs appears adequate to prove (or disprove) the diagnosis.

Adolescent↗

Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock.

BACKGROUND: Therapeutic hypothermia has been shown to increase survival after out-of-hospital cardiac arrest (OHCA). The trials documenting such benefit excluded patients with cardiogenic shock and only a few patients were treated with percutaneous coronary intervention prior to admission to an intensive care unit (ICU). We use therapeutic hypothermia whenever cardiac arrest patients do not wake up immediately after return of spontaneous circulation. METHODS: This paper reports the outcome of 50 OHCA patients with ventricular fibrillation admitted to a tertiary referral hospital for immediate coronary angiography and percutaneous coronary intervention when indicated. Patients were treated with intra-aortic balloon counterpulsation (IABP) (23 of 50 patients) if indicated. All patients who were still comatose were treated with therapeutic hypothermia at 32-34 degrees C for 24 h before rewarming. The end-points were survival and cerebral performance category (CPC: 1, best; 5, dead) after 6 months. RESULTS: Forty-one patients (82%) survived until 6 months. Thirty-four patients (68%) were in CPC 1 or 2, and seven (14%) were in CPC 3. Of the 23 patients treated with IABP, 14 (61%) survived with CPC 1 or 2. In patients not treated with IABP, 20 patients (74%) survived with CPC 1 or 2. Forty patients (80%) developed myocardial infarction. Percutaneous coronary intervention was performed in 36 patients (72%). CONCLUSION: In OHCA survivors who reached our hospital, the survival rate was high and the neurological outcome acceptable. Our results indicate that the use of therapeutic hypothermia is justified even in haemodynamically unstable patients and those treated with percutaneous coronary intervention.

Aged↗

Clinical research on the therapeutic effect of the electro-acupuncture treatment in patients with depression.

Electroacupuncture (EA) stimulation has been found to influence the brain (norepinephrine metabolism in experimental animals). Preliminary clinical research has shown that EA treatment is as effective as amitriptyline for patients with depression. In this study, two consecutive clinical studies on the treatment of depression with EA are conducted. The first study was double blind placebo controlled, in which 29 depressed inpatients were recruited. Patients were randomly divided into three groups: EA + placebo; amitriptyline; and EA + amitriptyline. They received EA and/or amitriptyline treatment for 6 weeks. The Hamilton Rating Scale for Depression, Clinical Global Impression and ASBERG scales for the side effect of antidepressants were used to evaluate the therapeutic efficacy and side effects. Based on the results and research protocol of the first study, a multi-centered collaborative study was conducted, in which 241 inpatients with depression were recruited. Patients were randomly divided into two treatment groups: the EA + placebo and the amitriptyline groups. The results from both studies showed that the therapeutic efficacy of EA was equal to that of amitriptyline for depressive disorders (P > 0.05). Electro-acupuncture had a better therapeutic effect for anxiety somatization and cognitive process disturbance of depressed patients than amitriptyline (P < 0.05). Moreover, the side effects of EA were much less than that of amitriptyline (P < 0.001). The article suggested that EA treatment was an effective therapeutic method for depressive disorders. Particularly, it was a treatment of choice for depressed patients who were unable to comply with the classic tricyclic antidepressants because of their anticholinergic side effects. The possible mechanism of EA treatment is discussed.

Adult↗

An investigation of professional advice advocating therapeutic sun exposure.

OBJECTIVE: To determine the prevalence of inappropriate professional advice advocating therapeutic sun exposure in infancy and the post-partum period. METHODS: Self-administered postal questionnaires were completed by doctors (n=130; 71% response) and nurses (n=285; 58.6% response) responsible for the care of post-parturient women in eight hospitals in metropolitan and regional Queensland (1999/2000). RESULTS: Both groups reported several risky beliefs about the therapeutic benefits of sun exposure including using sunlight to treat: cracked nipples (41.1% nurses, 46.2% doctors); neonatal jaundice (49.5%, 34.9%); nappy rash (23.3%, 19.5%); and acne (12.3%, 20.2%). Approximately 10% of nurses and doctors recommended sunlight to treat sore/cracked nipples from breastfeeding, while 42% recommended sun exposure to treat neonatal jaundice. Relatively few doctors and nurses who recommended therapeutic sun exposure stipulated sunning through a window. Subtropical residence was a significant predictor of recommending sunlight to treat cracked nipples (p=0.002) and nappy rash (p=0.0005) among nursing staff. Midwives were more likely to recommend sunlight for neonatal jaundice than other nurses (p=0.004). Obstetricians (p=0.046), older doctors (p=0.049) and those who qualified earlier (p=0.031) were more likely to recommend sunlight to treat nappy rash. Paediatricians and neonatologists were less likely to recommend sunlight to treat neonatal jaundice than obstetricians and other doctors (p=0.009). CONCLUSIONS AND IMPLICATIONS: An education program is needed to change the practices of health professionals who recommend therapeutic sun exposure and should coincide with a health promotion campaign aimed at reducing the prevalence of related risky beliefs among parents.

Adult↗

The therapeutic alliance--a conceptual analysis.

The role and function of the therapeutic alliance in psychotherapy has increasingly been the focus of clinicians' and researchers' interests over the last decade. Alliance concepts have, however, been criticized for lack of conceptual clarity. The paper presents a generic model as a heuristic means for clarifying the conceptual meaning of the therapeutic alliance. The model distinguishes between the personal relationship aspect, and the collaborative, task-related aspect of the alliance, with therapist, patient, and common contributions to each of these aspects. The model is compared to other alliance conceptualizations, and its implications for alliance theory and research are discussed. A content analysis of four widely used alliance scales in relation to the model shows the scales to represent conceptually different, yet overlapping constructs. It is argued that the componential nature of the therapeutic alliance will render difficult any interpretation of findings regarding the relationship between alliance and outcome in traditional process-outcome research. More complex research strategies guided by theory are called for, if the therapeutic alliance should remain a vital field of research.

Empathy↗

Child-therapist and parent-therapist alliance and therapeutic change in the treatment of children referred for oppositional, aggressive, and antisocial behavior.

BACKGROUND: We examined the therapeutic alliance in evidence-based treatment for children (N = 77, 19 girls, 58 boys, ages 6-14) referred clinically for oppositional, aggressive, and antisocial behavior. METHOD: Different alliances (child-therapist, parent-therapist) were assessed from each participant's perspective at two points over the course of treatment. Both the quality of the child-therapist and the parent-therapist alliance predicted therapeutic changes in the children; the parent-therapist alliance also predicted improvements in parenting practices in the home. RESULTS: The findings could not easily be attributed to the influence of other domains (socioeconomic disadvantage, parent psychopathology and stress, and severity of child dysfunction) known to predict therapeutic change or to rater effects (common rater variance) in the predictors and criteria. CONCLUSION: The therapeutic alliance warrants increased attention to understand the precise role in treatment and whether or how the alliance can be mobilized to enhance change.

Adolescent↗

Annotation: the therapeutic alliance--a significant but neglected variable in child mental health treatment studies.

BACKGROUND: There has been relatively little research into therapeutic alliance in child and adolescent mental health and virtually no incorporation of alliance measures as a variable in treatment trials in Child and Adolescent Mental Health Services (CAMHS). METHOD: A selective literature review on studies in therapeutic alliance in adulthood and childhood along with a theoretical formulation of possible mechanisms of alliance. RESULTS: Therapeutic alliance is reliably measurable both by observation and questionnaire methods at all points in the treatment cycle. In both adult and child studies it shows a consistent, albeit modest, association with treatment outcome. In specific adult studies it has shown a high predictive validity in relation to outcome compared to other variables. In child studies alliance is particularly salient in externalising disorder and predicts outcome of inpatient treatment. Child alliance and parental alliance are independent factors. Theoretical models of alliance outlined in this paper suggest testable hypotheses regarding predictors for positive and negative alliance. CONCLUSIONS: Therapeutic alliance in CAMHS is measurable and worth measuring. It is likely to be an important variable for treatment outcome studies and should be included in future trial designs.

Adolescent↗

Usefulness of contrast-enhanced ultrasonography with abdominal virtual ultrasonography in assessing therapeutic response in hepatocellular carcinoma treated with radiofrequency ablation.

OBJECTIVE: Contrast-enhanced computed tomography (CECT) is regarded as the gold standard for assessing the efficacy of radiofrequency ablation (RFA) against hepatocellular carcinoma (HCC). We evaluated the efficacy of virtual ultrasonography (VUS) with contrast-enhanced ultrasonography (CEUS) vs. CECT for assessing the response to RFA. MATERIALS AND METHODS: Study 1: The therapeutic responses in 22 patients with 26 HCC nodules were assessed by CEUS with VUS as well as by CECT. The efficacy of treatment was based on whether the safety margin was greater than 5 mm after RFA. Study 2: In seven patients with seven HCC nodules, the nodules were treated by RFA and the therapeutic efficacy was assessed by CEUS with VUS. The number of RFA sessions was assessed. RESULTS: Compared with CECT, CEUS with VUS had a specificity of 77%, a sensitivity of 91.6%, and an accuracy of 84%. When the therapeutic response to RFA was analyzed by CECT only, 1.86 +/- 0.69 assessments (mean) were required, while when response was assessed by CEUS with VUS, 1.14 +/- 0.38 CECT assessments were required (P = 0.03). CONCLUSION: CEUS with VUS is effective in assessing the therapeutic response to RFA of HCC. Moreover, the number of CECT scans required is reduced by this approach.

Abdomen↗