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W Kissling

Publications and source records attributed to W Kissling.

At least 19 recordsLinked to original sources
PubMed2006

Antidepressants for the negative symptoms of schizophrenia.

BACKGROUND: Negative symptoms are common in people with schizophrenia and are often difficult to treat with antipsychotic drugs. Treatment often involves the use of various add-on medications such as antidepressants. OBJECTIVES: To review the effects of the combination of antipsychotic and antidepressant drug treatment for management of negative symptoms in schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (January 2004). We also contacted authors of included studies in order to identify further trials. SELECTION CRITERIA: We included all randomised controlled trials comparing antipsychotic and antidepressant combinations with antipsychotics alone for the treatment of prominent negative symptoms in schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated the relative risk RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). MAIN RESULTS: We included five studies (all short-term, total N=190). We found no significant difference for 'leaving the study early for any reason' between the antipsychotic plus antidepressant combination and the control group (n=90, 3 RCTs, RR 3.0 CI 0.35 to 26.04). Leaving early due to adverse events (n=64, 2 RCTs, RR 5.0 CI 0.26 to 97.0) and leaving the study early due to inefficacy (n=34, 1 RCT, RR 3.0 CI 0.13 to 68.84) also showed no significant difference between the two treatment groups. In terms of clinical response, participants treated with the antipsychotic plus antidepressant medications showed a statistically significant greater improvement (n=30, 1 RCT, WMD -1.0 CI -1.61 to -0.39) and showed a significantly lower severity at endpoint (n=30, 1 RCT, WMD -0.9 CI -1.55 to -0.25) on the Clinical Global Impression Scale than those treated with antipsychotics alone. More people allocated to combination therapy had a clinically significant improvement in negative symptoms compared with those given antipsychotics and placebo (n=60, 2 RCTs, RR 0.56 CI 0.32 to 0.97, NNT 3 CI 3 to 34). Significant differences in favour of the combination therapy were seen in different aspects of negative symptoms: 'affective flattening' (n=30, 1 RCT, WMD -7.0 CI -10.37 to -3.63), 'alogia' (n=26, 1 RCT, WMD -3.00 CI -5.14 to -0.86) and 'avolition' (n=30, 1 RCT, WMD -3.0 CI -5.04 to -0.96). No statistically significant difference was found between treatment groups in regards to the outcome 'at least one adverse event' (n=84, 2 RCTs, RR 1.80 CI 0.66 to 4.90). For movement disorders and other adverse effects, no statistically significant differences were found in any of the studies that provided usable data on these outcomes. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, recurrence of negative symptoms, rehospitalisation or quality of life. There are no medium or long term data. AUTHORS' CONCLUSIONS: The combination of antipsychotics and antidepressants may be effective in treating negative symptoms of schizophrenia, but the amount of information is currently too limited to allow any firm conclusions. Large, pragmatic, well-designed and reported long term trials are justified.

Antidepressive Agents↗
PubMed2006

[Effects of a shared decision making model in psychiatric and neurologic practice].

Involving patients in medical decisions is increasingly being advocated in medical fields other than psychiatry and neurology. A model of shared decision making might prove to be an ideal way of bridging the gap between patient-centred and evidence-based medicine. This report provides a survey of this shared decision making model and a discussion of its implications in the fields of mental health and neurology.

Adaptation, Psychological↗
PubMed2006

Shared decision making for in-patients with schizophrenia.

OBJECTIVE: Patients' participation in treatment planning is being increasingly advocated in mental health. The model of "Shared Decision Making" (SDM) is proposed as a promising method of engaging patients in medical decisions and improving health-related outcomes. In the present study, the feasibility and effects of SDM for in-patients with schizophrenia should be evaluated. METHOD: Randomized controlled trial comparing a SDM program with routine care (n = 107). RESULTS: The intervention studied was feasible for most of the patients and did not take up more of the doctors' time. Patients in the intervention group had a better knowledge about their disease (P = 0.01) and a higher perceived involvement in medical decisions (P = 0.03). The intervention increased the uptake of psychoeducation (P = 0.003). CONCLUSION: Sharing medical decisions with acutely ill in-patients with schizophrenia is in many cases possible and improves important treatment patterns. This might help in destigmatizing this group of patients and improving schizophrenia-related health outcomes.

Acute Disease↗
PubMed2005

European psychiatric treatment guidelines: is the glass half full or half empty?

PURPOSE: We assessed the quality of European treatment guidelines in the field of mental health that have been produced by national psychiatric associations. The main focus was the question of whether the development process of the guidelines followed basic principles of evidence-based medicine. METHODS: Sixty-one European clinical practice guidelines from 14 countries, published between 1998 and 2003, were assessed using the 'Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument'. The domain score was calculated for each of the six domains of the AGREE instrument. The seven items of the domain "rigor of development" and one additional item concerning national particularities were assessed in detail. RESULTS: The mean scores in the six domains were rather low, although the quality varied among the different guidelines. The highest mean score was obtained in the domain clarity and presentation (70.8% S.D. 23.5), the lowest on editorial independence (19.7% S.D. 29.3). The recommendations of about half of the assessed guidelines could be considered to be evidence-based. CONCLUSION: The assessed guidelines showed a broad range of quality: some producers attached importance to an evidence-based development process; but in spite of this, a large number of guidelines were only of middling quality. As national particularities are only rarely mentioned and the development process of guidelines is complex, an international collaboration that aims toward the production of shareable guidelines might be promising.

Europe↗
PubMed2005

Direct transition to long-acting risperidone--analysis of long-term efficacy.

This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as < or =3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group.715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9+/-22.7. This was significantly reduced after 1 month (67.7 +/-22.3, p< or =0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7+/-21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for < or = 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.

Adult↗
PubMed2004

Language bias in neuroscience--is the Tower of Babel located in Germany?

In internal medicine German authors tend to publish randomized controlled trials (RCTs) with non-significant findings in German journals, RCTs with significant findings in international journals. In the neurosciences a similar trend was seen but the findings were not statistically significant. The reason for this inconclusive finding might be the low number of RCTs published in German.

Germany↗
PubMed2003

Lithium for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium. OBJECTIVES: To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data. SELECTION CRITERIA: All randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Continuous data were analysed using weighted mean differences (WMD). MAIN RESULTS: The review currently includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data, because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events. REVIEWER'S CONCLUSIONS: There is no randomised trial based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but it justifies further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.

Antipsychotic Agents↗
PubMed2003

New generation antipsychotics for first episode schizophrenia.

BACKGROUND: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. OBJECTIVES: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question.

Antipsychotic Agents↗
PubMed2003

Shared decision making in psychiatry.

OBJECTIVE: In other medical fields, 'shared decision making' (a strategy for including patients in therapeutic decision processes) has been studied for several years now. This survey presents the potential of shared decision making for psychiatry. METHOD: Literature search. RESULTS: Research in other medical fields shows that shared decision making positively influences patients' satisfaction as well as health outcomes. The application of shared decision making to psychiatry is still in the initial stage. CONCLUSION: Evidence that shared decision making can be successfully practiced in psychiatry would contribute to an improved inclusion of psychiatric patients in therapeutic decisions and thereby help to implement basic rights of a group of patients who have not sufficiently benefited from consumer empowerment in other medical fields.

Antipsychotic Agents↗
PubMed2003

Are the second-generation antipsychotics cost-effective? A critical review on the background of different health systems.

BACKGROUND: Despite clinical advantages over conventional compounds, second-generation antipsychotics are prescribed less frequently in some European countries than in the United States because of their higher acquisition price and the current cost-containment strategies of many European health systems. This has been criticized on the grounds that the higher acquisition costs of the new antipsychotics might be more than outweighed by savings in other fields, e. g., through a reduction in rehospitalizations or indirect costs. METHOD: In order to create an empirical basis for this discussion, a review of the results of pharmacoeconomic studies (mostly cost-effectiveness studies) comparing second-generation with conventional antipsychotics was undertaken. RESULTS: Of the 35 studies identified, most report at least cost-neutrality of the new antipsychotics (in many cases clozapine) that is due to reductions in hospitalization costs. These results cannot be generalized, however, because of methodological shortcomings such as small patient samples and study designs with low validity, and especially because of a lack of studies performed outside the U.S. It is shown that results from studies in the U.S. cannot be generalized to other health systems in Europe or in developing countries. Furthermore, only a few findings on newer second-generation antipsychotics other than clozapine are reported, and no study investigated indirect costs, which play a major role because of the early onset and chronicity of schizophrenia. CONCLUSION: Until now, there has been no sufficient evidence for the superior cost-effectiveness of atypical antipsychotics in European countries. Considering the importance of this topic for health politics, more cost-effectiveness studies in European countries are urgently needed. But even if economic superiority of the second-generation antipsychotics cannot be demonstrated in such studies, their use is nevertheless indicated with respect to patient's well-being.

Antipsychotic Agents↗
PubMed2003

Are patients with schizophrenia under-treated with second-generation antipsychotics? A pilot study of the prescription practices of German psychiatrists.

INTRODUCTION: Patients' and relatives' associations, psychiatrists, and pharmaceutical companies are complaining about a deficiency in the care of psychiatric patients with innovative medications in Germany. They estimate that only about 10- 30 % of all patients with schizophrenia receive second-generation antipsychotics, a figure that lies significantly below the international average. METHODS: In order to determine the frequency of use of second-generation antipsychotics in the actual care of schizophrenic patients, we conducted the following investigations:--Discharge papers of schizophrenic inpatients from a university hospital and from a district hospital were studied with regard to the antipsychotic discharge medication.--Practicing psychiatrists were contacted and asked whether during the first 3 months after discharge they had continued the antipsychotic discharge medication that was proposed by the hospital. RESULTS: The investigation of a total of 200 discharge papers and the subsequent questioning of the psychiatrists who carried out the follow-up treatment showed that 166 patients (83 %) received a second-generation antipsychotic upon discharge. Only 5 % of these patients were switched to conventional antipsychotics in the outpatient treatment. Thus, contrary to our expectations, there was no noteworthy change from second-generation to classical antipsychotics. DISCUSSION: Therefore, in the sample analyzed the second-generation antipsychotics were far more frequently prescribed than would have been expected according to general estimates, and it was not possible to verify the often-heard complaints of an under-treatment with second generations in this study. Our findings suggest, however, that only 60 % of the patients still receive their discharge medication 3 months after discharge from the hospital. This raises the important question as to how continuity of the antipsychotic treatment could be better ensured.

Adult↗
PubMed2001

Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy.

Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Variability of this response is a major problem. Fatal adverse drug reactions have been reported to be the fourth leading cause of death in the US. In depression, 30-40% of all patients do not respond sufficiently to the initial treatment and it can take up to 6 weeks for them to be identified. Much knowledge has been gathered throughout the last 3 decades about the genetic basis of pharmacokinetic variability. Genetic tests suitable for the routine laboratory are now available for some important metabolizing enzymes (e.g., CYP2D6, CYP2C19) identifying those individuals who are slow or fast metabolizers of certain drugs, many of which are widely used in the treatment of depression (e.g., tricyclic antidepressants). The possible use of these tests in the clinical practice of monitoring antidepressant therapy is discussed in relation to older phenotyping methods and therapeutic drug monitoring.Less well studied than the genetics of pharmacokinetics is the genetic basis of pharmacodynamic variability. As selective serotonin reuptake inhibitors (SSRI) have a wide therapeutic index, pharmacokinetic variability usually does not explain insufficient response to therapy. Recently, some excitement was caused by reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy with SSRIs as this could provide an interesting diagnostic tool in assessing the chances of response to the most popular group of antidepressants at present. Current knowledge in this young field of research is summarized.

Antidepressive Agents↗
PubMed2001

The effect of family interventions on relapse and rehospitalization in schizophrenia--a meta-analysis.

Twenty-five intervention studies were meta-analytically examined regarding the effect of including relatives in schizophrenia treatment. The studies investigated family intervention programs to educate relatives and help them cope better with the patient's illness. The patient's relapse rate, measured by either a significant worsening of symptoms or rehospitalization in the first years after hospitalization, served as the main study criterion. The main result of the meta-analysis was that the relapse rate can be reduced by 20 percent if relatives of schizophrenia patients are included in the treatment. If family interventions continued for longer than 3 months, the effect was particularly marked. Furthermore, different types of comprehensive family interventions have similar results. The bifocal approach, which offers psychosocial support to relatives and schizophrenia patients in addition to medical treatment, was clearly superior to the medication-only standard treatment. The effects of family interventions and comprehensive patient interventions were comparable, but the combination did not yield significantly better results than did a treatment approach, which focused on either the patient or the family. This meta-analysis indicates that psychoeducational interventions are essential to schizophrenia treatment.

Adaptation, Psychological↗
PubMed2001

Doxepin plasma concentrations: is there really a therapeutic range?

Despite the introduction of numerous new agents, tricyclic antidepressants remain an important option for the treatment of depression. Doxepin is still in wide use, and determining its concentration is a standard procedure in many psychiatric clinics. Some widely cited reviews indicate a therapeutic range from 150 to 250 ng/mL (parent plus desmethyl metabolite). The vast majority of the authors' patients fell short of these concentrations under customary doses. To resolve this issue, the authors' serum-level databank was analyzed, a questionnaire was sent to U.S. and German psychiatric university departments and laboratories, and the literature was reviewed. The main results were the following: (1) Only 9% of all samples analyzed (N = 217) displayed plasma levels (high-performance liquid chromatography) between 150 and 250 ng/mL; 88% were subtherapeutic. The mean doxepin + desmethyldoxepin steady-state serum concentration was 89+/-75 ng/mL (N = 32, doxepin >3 weeks). The mean daily dose was 143+/-30 mg. There was no correlation between concentrations and improvement. (2) A wide variety of recommendations is given by the different university departments (10-1,000 ng/mL). (3) According to the studies published to date, there is not enough evidence for recommending a therapeutic range. The preliminary suggestions given in some influential reviews have been widely adopted without critical re-evaluation. Compared with the concentrations found in the original studies, the therapeutic ranges suggested are too high. A methodologically sound study to determine a therapeutic range is required for the rational monitoring of this drug. Meanwhile, a preliminary working range of 50 to 250 ng/mL is proposed on the basis of critical reassessment of published data.

Aged↗
PubMed2001

Who is interested in the quality of everyday psychiatric care?

In the past 50 years the treatment possibilities have drastically improved, but the treatment results achieved under everyday care conditions mainly lag far behind those that could actually be achieved. This efficacy-effectiveness gap is at present the main obstacle to achieving optimal outcome in psychiatry. In this editorial, several causative factors for this gap are named and suggestions are made as to what should be done to fulfill the outcome that is achievable according to today's state of knowledge. Estimates indicate that at least a 25% improvement of important outcome indicators (e.g. yearly relapse rates) could be achieved.

Forecasting↗
PubMed2001

Quality management in psychiatry.

Over the past 50 years, treatment possibilities in psychiatry have drastically improved, but the results we actually achieve under everyday treatment conditions fall far short of what could be accomplished. Quality management represents a suitable method of reducing this gap. Although it has been successfully practiced in other medical disciplines for a long time, its implementation in psychiatry has previously been restricted to pilot projects. Quality management programs in psychiatry have been slow to be accepted because, up to now, only a few mental health professionals have received training in quality management techniques. In order to compensate for this information deficit and to familiarize psychiatrists and other mental health care workers with this increasingly important topic, we will provide in this paper a brief survey of the most important principles and techniques of quality management. This information should encourage psychiatrists to apply this new method to their own areas of responsibility. The results of one of our own studies on schizophrenic outpatients, which are presented at the end of the paper, are intended to show that the outcome can be improved and costs reduced by implementing quality management programs in psychiatry.

Ambulatory Care↗
PubMed2000

[Prevention of relapse in schizophrenia is discontinued too soon. Many colleagues make this mistake!].

OBJECTIVE: The recommendations given by general practitioners in the treatment of schizophrenia were investigated empirically and compared with those given by psychiatrists as well as with the accepted standards for the prophylactic treatment of schizophrenic psychoses. METHOD: In an interview based on case reports, 64 randomly selected general practitioners in private practice were asked 6 questions on the treatment of schizophrenic psychoses. RESULTS: 75% of the general practitioners recommend a duration of prophylactic measures that is significantly shorter than that recommended by international standards, and also significantly shorter than that recommended by psychiatrists. This undertreatment correlates with an overestimation of the risk of side effects and--at least in first-time patients--an underestimation of the relapse risk. CONCLUSION: Despite a number of significant differences between general practitioners and psychiatrists, both groups fall far short of international treatment standards in terms of recommended duration of prophylaxis, both underestimate the relapse risk and overestimate the risk of side effects. Possible approaches to improving the quality of relapse prevention in schizophrenia are, for example, joint educational activities for family doctors and psychiatrists, and the establishment and implementation of joint treatment guidelines.

Adult↗