Enhanced growth factor expression in chronic diabetic wounds treated by cold atmospheric plasma.

AIMS: Cold atmospheric plasma (CAP) has been proven to enhance wound healing in superficial, chronically infected, diabetic foot ulcers. We aimed to investigate the molecular drivers responsible for this macroscopically observed improvement in diabetic wound healing. METHODS: Wound exudate was available from each change of dressing within a prospective, randomised, patient-blinded clinical trial. Specific protein level analyses were conducted via multiplex ELISA for wound samples of a representative subcohort (placebo: n = 13; CAP: n = 14). Expression of fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor A (VEGF-A), cytokines and matrix metalloproteinases (MMPs) were evaluated over a treatment period of about 14 days. RESULTS: Analysis revealed increased levels of the growth factors FGF-2 (placebo: median 46.9 range [32.0-168.6] AU vs. CAP: 113.7[55.8-208.1] AU) and VEGF-A (placebo: 79.7 [52.4-162.7] AU vs. CAP: 120.8 [51.1-198.1] AU) throughout the treatment period and in head-to-head comparison in a daily assessment. CAP-treated wounds showed increased levels of tumour necrosis factor-alpha, interleukins 1α and 8. However, the total protein amounts were not significantly elevated. The total protein amounts of MMPs were not altered by CAP. CONCLUSIONS: Induction of crucial growth factors, like FGF-2 and VEGF-A, and interleukins appears to be an important component of CAP-mediated promotion of granulation, vascularisation and reepithelialisation in the diabetic foot. These findings demonstrate for the first time that CAP-mediated growth factor induction also occurs in persons with diabetes, as previously described only in several in vitro and rodent experiments. Clinical Trial registration KPWTRIAL: NCT04205942, ClinicalTrials.gov.

[Flexible and integrative treatment in psychiatry: implementation of specific care components at model and standard care clinics in Germany (PsychCare study)]. / Settingübergreifende Behandlung in der Psychiatrie: Umsetzung spezifischer Versorgungsmerkmale an Kliniken der Modell- und Regelversorgung (PsychCare-Studie).

BACKGROUND: Since 2003 a new remuneration and care model has been implemented in currently 22 psychiatric clinics in Germany, which provides flexible and integrative treatment (FIT) across different settings of treatment, including assertive outreach care. The FIT is based on a global treatment budget covering costs for all psychiatric hospital services and is related to the number of patients treated per year. Previous research identified 11 program components that describe treatment structures and processes of FIT. The present analysis quantitatively compared FIT with standard care, aiming to validate these components. METHODS: As part of the PsychCare study, grading according to FIT-specific components was carried out and comparatively analyzed in nine hospitals that used FIT and seven hospitals of standard care. The FIT models were examined in depth in subgroups, which were divided according to the share of the FIT model in the total hospital budget. RESULTS: Of the 11 FIT program components 7 (flexible care management across settings, therapeutic group sessions across all settings, outreach home care, involvement of informal caregivers, accessibility of services, cooperation across sectors and expansion of professional expertise) showed a high statistical differentiation. These differences were even stronger in the subgroup of those hospitals that had a model contract with all health insurers. CONCLUSION: Specific components of FIT are suitable for evaluating the quality of implementation of intersectoral, flexible and outreach psychiatric care.

Implementation, efficacy, costs and processes of inpatient equivalent home-treatment in German mental health care (AKtiV): protocol of a mixed-method, participatory, quasi-experimental trial.

BACKGROUND: Over the last decades, many high-income countries have successfully implemented assertive outreach mental health services for acute care. Despite evidence that these services entail several benefits for service users, Germany has lagged behind and has been slow in implementing outreach services. In 2018, a new law enabled national mental health care providers to implement team-based crisis intervention services on a regular basis, allowing for different forms of Inpatient Equivalent Home Treatment (IEHT). IEHT is similar to the internationally known Home Treatment or Crisis Resolution Teams. It provides acute psychiatric treatment at the user's home, similar to inpatient hospital treatment in terms of content, flexibility, and complexity. METHODS/DESIGN: The presented naturalistic, quasi-experimental cohort study will evaluate IEHT in ten hospitals running IEHT services in different German regions. Within a multi-method research approach, it will evaluate stakeholders' experiences of care, service use, efficacy, costs, treatment processes and implementation processes of IEHT from different perspectives. Quantitative surveys will be used to recruit 360 service users. Subsequently, 180 service users receiving IEHT will be compared with 180 matched statistical 'twins' receiving standard inpatient treatment. Assessments will take place at baseline as well as after 6 and 12 months. The primary outcome is the hospital re-admission rate within 12 months. Secondary outcomes include the combined readmission rate, total number of inpatient hospital days, treatment discontinuation rate, quality of life, psycho-social functioning, job integration, recovery, satisfaction with care, shared decision-making, and treatment costs. Additionally, the study will assess the burden of care and satisfaction with care among relatives or informal caregivers. A collaborative research team made up of researchers with and without lived experience of mental distress will conduct qualitative investigations with service users, caregivers and IEHT staff teams to explore critical ingredients and interactions between implementation processes, treatment processes, and outcomes from a stakeholder perspective. DISCUSSION: By integrating outcome, process and implementation research as well as different stakeholder perspectives and experiences in one study, this trial captures the various facets of IEHT as a special form of home treatment. Therefore, it allows for an adequate, comprehensive evaluation on different levels of this complex intervention. TRIAL REGISTRATION: Trial registrations: 1) German Clinical Trials Register (DRKS), DRKS000224769. Registered December 3rd 2020, https://www.drks.de/drks_web/setLocale_EN.do ; 2) ClinicalTrials.gov, Identifier: NCT0474550 . Registered February 9th 2021.

[Implementation of New Flexible and Integrative Psychiatric Care Models (According to §64b SGB V) in Rural Northern Germany in Comparison to Federal Territory]. / Analyse von Implementierungsmerkmalen psychiatrischer Modellvorhaben (nach §64b SGB V) in Schleswig-Holstein im Vergleich zum Bundesgebiet.

AIM: New treatment models (according to §64b German Social Code) have been introduced in Germany to improve flexible and integrated forms of psychiatric care. The aim of this study was to analyse the specific conditions under which many of these models have been implemented in the federal state of Schleswig-Holstein (SH) in comparison to other federal regions. METHODS: A standardized survey reached 383 patients in seven psychiatric departments, among them three departments in SH. In addition, routine data and data evaluating the grade of implementation in these departments were analysed. RESULTS: Departments in SH showed more developed implementation processes, compared with departments in other regions. Implemented changes were perceived and evaluated as being better by patients in SH. CONCLUSIONS: Implementation processes of flexible and integrated forms of care according to §64b were particularly successful in SH. Extensive political support is discussed as a major reason, among others, for this development.

[Implementation and Stakeholders' Experiences with Home Treatment in Germany's Integrative and Flexible Psychiatric Care Models - A Mixed-Methods Study]. / Implementierungsstand und Erfahrungen der Stakeholder mit der Zuhause-Behandlung in psychiatrischen Modellvorhaben (nach §64b SGB V) ­ Eine Mixed-Methods Untersuchung.

OBJECTIVE: This paper seeks to illustrate current implementation of and the stakeholders' experiences with Home Treatment (=HT) according to §64b of the German Social Code Book V (=SGB V). METHODS: 381 Patients from 8 hospitals were questioned about their experiences and evaluation of HT using a standardized questionnaire (SEPICC-Scale). Further interviews and focus groups with 37 participants (including users, carers and employees) were thematically analysed. In addition, structural and performance data were collected from participating hospitals and HT teams. RESULTS: HT according to §64b SGB V is implemented quite heterogeneously, especially between rural and urban catchment areas. It provides a long-term, cross-sectoral care, which seems to strengthen the integration of patients' everyday life, treatment flexibility and continuity of care. After having experienced HT once, it is generally rated better. CONCLUSION: An important strength of HT (§64b SGB V) is its adaption to the users' needs and to regional distinctions. Implications for the implementation of outreach services on a larger scale in Germany can be drawn.

Dopamine D2 Receptor Occupancy Estimated From Plasma Concentrations of Four Different Antipsychotics and the Subjective Experience of Physical and Mental Well-Being in Schizophrenia: Results From the Randomized NeSSy Trial.

BACKGROUND: Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). METHODS: An innovative double randomization process was used for allocation of patients to the specific treatment groups. Plasma drug concentrations were measured after 6 and 24 weeks of treatment to obtain the estimated D2-RO (eD2-RO) relative to literature values. We made an exploratory analysis of associations between eD2-RO and subjective well-being scores. One hundred two blood samples from 69 patients were available for the analysis. Because of the lack of a satisfactory occupancy model for quetiapine, only haloperidol, flupentixol, and olanzapine treatment groups were pooled, whereas aripiprazole data were analyzed separately, because of its partial agonistic properties. RESULTS: In the pooled antagonist group, eD2-RO correlated negatively with the summarized well-being score. In a more detailed analysis, this association could be confirmed for all first-generation antipsychotic-treated patients, but not for the separate second-generation antipsychotic groups. In the aripiprazole group, higher eD2-RO was associated with impaired physical well-being, but had no association with mental well-being. CONCLUSIONS: Our results suggest that high plasma levels and consequently high occupancy at D2 receptors are disadvantageous for subjective well-being, as distinct from the objective extrapyramidal side effects. To minimize patients' malaise, which disfavors adherence, implementation of therapeutic drug monitoring in the clinical routine may be useful.

Effectiveness and cost-effectiveness of an integrated care program for schizophrenia: an analysis of routine data.

In Germany, a regional social health insurance fund provides an integrated care program for patients with schizophrenia (IVS). Based on routine data of the social health insurance, this evaluation examined the effectiveness and cost-effectiveness of the IVS compared to the standard care (control group, CG). The primary outcome was the reduction of psychiatric inpatient treatment (days in hospital), and secondary outcomes were schizophrenia-related inpatient treatment, readmission rates, and costs. To reduce selection bias, a propensity score matching was performed. The matched sample included 752 patients. Mean number of psychiatric and schizophrenia-related hospital days of patients receiving IVS (2.3 ± 6.5, 1.7 ± 5.0) per quarter was reduced, but did not differ statistically significantly from CG (2.7 ± 7.6, 1.9 ± 6.2; p = 0.772, p = 0.352). Statistically significant between-group differences were found in costs per quarter per person caused by outpatient treatment by office-based psychiatrists (IVS: €74.18 ± 42.30, CG: €53.20 ± 47.96; p < 0.001), by psychiatric institutional outpatient departments (IVS: €4.83 ± 29.57, CG: €27.35 ± 76.48; p < 0.001), by medication (IVS: €471.75 ± 493.09, CG: €429.45 ± 532.73; p = 0.015), and by psychiatric outpatient nursing (IVS: €3.52 ± 23.83, CG: €12.67 ± 57.86, p = 0.045). Mean total psychiatric costs per quarter per person in IVS (€1117.49 ± 1662.73) were not significantly lower than in CG (€1180.09 ± 1948.24; p = 0.150). No statistically significant differences in total schizophrenia-related costs per quarter per person were detected between IVS (€979.46 ± 1358.79) and CG (€989.45 ± 1611.47; p = 0.084). The cost-effectiveness analysis showed cost savings of €148.59 per reduced psychiatric and €305.40 per reduced schizophrenia-related hospital day. However, limitations, especially non-inclusion of costs related to management of the IVS and additional home treatment within the IVS, restrict the interpretation of the results. Therefore, the long-term impact of this IVS deserves further evaluation.

Evaluation of new flexible and integrative psychiatric treatment models in Germany- assessment and preliminary validation of specific program components.

BACKGROUND: Flexible and integrative treatment (FIT) models are rather novel in German mental health care. This study aimed at identifying and evaluating empirically based, practicable, and quantifiable program components that describe the specific treatment structures and processes of German FIT models. METHODS: A multi-step, iterative research process, based on Grounded Theory Methodology (GTM), was used to identify and operationalise components. A complex algorithm and expert-interviews were applied to quantify the relative weight of each component and to develop a sum score. Face and content validity were examined and internal consistency was tested by Cronbach's α coefficient. RESULTS: Ten of eleven FIT components could be operationalised, quantified and united in the total score. All operationalised components showed sufficient face and content validity and eight components had a good reliability. CONCLUSIONS: The components are a first step in the process of operationally defining German FIT models. They considerably overlap with various critical ingredients of international FIT models and may serve as a theoretical basis for constructing fidelity tools and research guides to enable process and outcome evaluation of German FIT models.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

BACKGROUND: The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. METHODS: The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. RESULTS: In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. CONCLUSION: The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful.

[Inpatient Equivalent Home Treatment (IEHT) compared to inpatient psychiatric treatment: 12-month follow-up results of a retrospectively matched cohort study using propensity score]. / Stationsäquivalente Behandlung (StäB) im Vergleich mit vollstationärer Behandlung: 12-Monats-Follow-up Ergebnisse einer mittels Propensity-Score gematchten retrospektiven Kohortenstudie.

AIM OF THE STUDY: Comparison of psychiatric services use in the 12-month follow-up period between Inpatient Equivalent Home Treatment (IEHT) and inpatient psychiatric treatment. METHODS: In a retrospective 12-month follow-up study, 223 patients from the Inpatient Equivalent Home Treatment (IEHT) intervention group (IG) were compared to a matched inpatient control group (CG) on their utilization of psychiatric services. RESULTS: The inpatient readmission rate in the IG was significantly 11% lower than in the CG. The number of treatment days in the IG was significantly lower than in the CG. In the IG, psychiatric services at the outpatient clinic were used significantly more often for the first time than in the CG. CONCLUSION: The present study suggests that IEHT is superior to inpatient treatment in terms of the risk of inpatient readmission and the duration of inpatient treatment days. An outpatient services use effect following IEHT is observed.

[IEHT or inpatient treatment? - First results of the multicenter AKtiV study on inpatient-equivalent home treatment regarding the study population and index treatment]. / StäB oder Station? ­ Erste Ergebnisse zur Studienpopulation und zur Behandlung im Rahmen der multizentrischen AKtiV-Studie zur stationsäquivalenten Behandlung.

AIM: The quasi-experimental AKtiV study investigates the effects inpatient-equivalent home treatment (IEHT). This paper describes the study population based on demographic and clinical parameters at baseline and compares the index treatment. METHODS: Over a period of 12 months 200 IEHT users were included in the intervention group (IG) and 200 inpatients were included in the control group (CG). The comparability of the two groups was ensured by propensity score matching (PSM). RESULTS: In addition to the PSM variables, IG and CG did not differ significantly from each other variables at study inclusion. The duration of the index treatment was significantly longer in the IG (M=37.2 days) compared to the CG (M=27.9 days; p<0.001). CONCLUSION: The similarity of the two groups enables comparisons over 12 months, investigating IEHT effects on long-term outcomes.

Premature termination, satisfaction with care, and shared decision-making during home treatment compared to inpatient treatment: A quasi-experimental trial.

BACKGROUND: Inpatient equivalent home treatment (IEHT), implemented in Germany since 2018, is a specific form of home treatment. Between 2021 and 2022, IEHT was compared to inpatient psychiatric treatment in a 12-months follow-up quasi-experimental study with two propensity score matched cohorts in 10 psychiatric centers in Germany. This article reports results on the treatment during the acute episode and focuses on involvement in decision-making, patient satisfaction, and drop-out rates. METHODS: A total of 200 service users receiving IEHT were compared with 200 matched statistical "twins" in standard inpatient treatment. Premature termination of treatment as well as reasons for this was assessed using routine data and a questionnaire. In addition, we measured patient satisfaction with care with a specific scale. For the evaluation of patient involvement in treatment decisions, we used the 9-item Shared Decision Making Questionnaire (SDM-Q-9). RESULTS: Patients were comparable in both groups with regard to sociodemographic and clinical characteristics. Mean length-of-stay was 37 days for IEHT and 28 days for inpatient treatment. In both groups, a similar proportion of participants stopped treatment prematurely. At the end of the acute episode, patient involvement in decision-making (SDM-Q-9) as well as treatment satisfaction scores were significantly higher for IEHT patients compared to inpatients. CONCLUSIONS: Compared to inpatient care, IEHT treatment for acute psychiatric episodes was associated with higher treatment satisfaction and more involvement in clinical decisions.

[Does Inpatient Equivalent Home Treatment lead to higher satisfaction? Results on satisfaction of persons involved in treatment within the Multi-center AKtiV Study]. / Stößt die Behandlung zu Hause auf größere Zufriedenheit? Ergebnisse zur Zufriedenheit der an der Behandlung beteiligten Personengruppen im Rahmen der multizentrischen AKtiV-Studie.

This part of the AKtiV Study focuses on treatment satisfaction of patients and their relatives within Inpatient Equivalent Home Treatment (IEHT) and regular treatment. Stress of relatives and job satisfaction and workload of employees in IEHT is also considered. Relevant Parameters were collected via established as well as newly adapted questionnaires at the end of treatment. Patients and relatives in IEHT are significantly more satisfied. The stress experienced by relatives is reduced in both forms of treatment. Employees in IEHT are generally very satisfied, although there is no correlation with the satisfaction of relatives and patients. Known limitations of satisfaction surveys must be taken into account. In general these results encourage the expansion and continuous development of this new form of treatment in Germany.

Pathway-controlled fast-track rehabilitation after total knee arthroplasty: a randomized prospective clinical study evaluating the recovery pattern, drug consumption, and length of stay.

PURPOSE: To investigate fast-track rehabilitation concept in terms of a measurable effect on the early recovery after total knee arthroplasty (TKA). METHODS: This was an open, randomized, prospective clinical study, comparing the fast-track rehabilitation--a pathway-controlled early recovery program (Joint Care(®))--with standard postoperative rehabilitation care, after TKA. Overall, 147 patients had TKA (N = 74 fast-track rehabilitation, N = 73 standard rehabilitation). The fast-track rehabilitation patients received a group therapy, early mobilization (same day as surgery) and 1:1 physiotherapy (2 h/day). Patient monitoring occurred over 3 months (1 pre- and 4 post-operative visits). The standard rehabilitation group received individual postoperative care according to the existing protocol, with 1:1 physiotherapy (1 h/day). The cumulative American Knee Society Score (AKSS) was the primary evaluation variable, used to detect changes in joint function and perception of pain. The secondary evaluation variables were WOMAC index score, analgesic drug consumption, length of stay (LOS), and safety. RESULTS: After TKA, patients in the fast-track rehabilitation group showed enhanced recovery compared with the standard rehabilitation group, as based on the differences between the groups for the cumulative AKSS (p = 0.0003), WOMAC index score (<0.0001), reduced intake of concomitant analgesic drugs, reduced LOS (6.75 vs. 13.20 days, p < 0001), and lower number of adverse events. CONCLUSION: For TKA, implementation of pathway-controlled fast-track rehabilitation is achievable and beneficial as based on the AKSS and WOMAC score, reduced intake of analgesic drugs, and reduced LOS.

Transcatheter mitral valve implantation versus conventional redo surgery for degenerated mitral valve prostheses and rings in a multicenter registry.

OBJECTIVES: Degeneration of mitral prostheses/rings may be treated by redo surgery, and, recently, by transcatheter valve-in-valve/ring implantation. This multicenter registry presents results of transcatheter valve-in-valve and repeat surgery for prostheses/rings degeneration. METHODS: Data provided by 10 German heart centers underwent propensity score-matched retrospective analysis. The primary endpoint was 30-day/midterm mortality. Perioperative outcome was assessed according to the Mitral Valve Academic Research Consortium criteria. Further, the influence of moderate or greater tricuspid regurgitation (TR) on 30-day/midterm mortality was analyzed. RESULTS: Between 2014 and 2019, 273 patients (79 transcatheter mitral valve-in-valve [TM-ViV] and 194 redo mitral valve replacement [Re-MVR]) underwent repeat procedure for mitral prosthesis/ring degeneration. Propensity score matching distinguished 79 patient pairs. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II-predicted risk was 15.7 ± 13.7% in the TM-ViV group and 15.0% ± 12.7% in the Re-MVR group (P = .5336). TM-ViV patients were older (74.73 vs 72.2 years; P = .0030) and had higher incidence of atrial fibrillation (54 vs 40 patients; P = .0233). Severe TR incidence was similar (17.95% in TM-ViV vs 14.10%; P = .1741). Sixty-eight TM-ViV patients previously underwent mitral valve replacement, whereas 41 Re-MVR patients underwent valve repair (P < .0001). Stenosis was the leading degeneration mechanism in 42 TM-ViV versus 22 Re-MVR patients (P < .0005). The 30-day/midterm mortality did not differ between groups. Moderate or greater TR was a predictor of total (odds ratio [OR], 4.36; P = .0011), 30-day (OR, 3.76; P = .0180), and midterm mortality (OR, 4.30; P = .0378), irrespective of group. CONCLUSIONS: In both groups, observed mortality was less than predicted. Redo surgery enabled treatment of concomitant conditions, such as atrial fibrillation or TR. TR was shown to be a predictor of total, 30-day, and midterm mortality in both groups.

A new outlier identification test for method comparison studies based on robust regression.

The identification of outliers in method comparison studies (MCS) is an important part of data analysis, as outliers can indicate serious errors in the measurement process. Common outlier tests proposed in the literature usually require a homogeneous sample distribution and homoscedastic random error variances. However, datasets in MCS usually do not meet these assumptions. In this work, a new outlier test based on robust linear regression is proposed to overcome these special problems. The LORELIA (local reliability) residual test is based on a local, robust residual variance estimator, given as a weighted sum of the observed residuals. The new test is compared to a standard test proposed in the literature by a Monte Carlo simulation. Its performance is illustrated in examples.

Flexible and Integrative Psychiatric Care Based on a Global Treatment Budget: Comparing the Implementation in Germany and Poland.

Background: The past decade has witnessed the establishment of flexible and integrative treatment (FIT) models in 55 German and Polish psychiatric catchment areas. FIT is based on a global treatment budget (GTB), which integrates funding of all acute psychiatric hospital services for a regional population. Prior research has identified 11 specific program components of FIT in Germany. In this paper we aim at assessing the applicability of these components to the Polish context and at comparatively analysing FIT implementation in Poland and Germany. Methods: Qualitative interviews about the applicability of the 11 FIT-specific components were conducted with the program managers of the Polish FIT models (n = 19). Semi-quantitative data on the FIT-specific components were then collected in 19 Polish and 10 German FIT models. We assessed the grading of each component, their overall degree of implementation and compared them between the two countries. In all study hospitals, structural and statistical parameters of service delivery were collected and compared. Results: The qualitative results showed that the German FIT-specific components are in principle applicable to the polish context. This allowed the comparative assessment of components grading and degree of implementation, which showed only subtle discrepancies between German and Polish FIT models. The little discrepancies point to specific aspects of care such as home treatment, peer support, and cooperation with non-clinical and social welfare institutions that should be further integrated in the components' definition. Conclusions: The specific program components of FIT as first defined from the German experience, serves as a powerful tool to measure, and evaluate implementation of integrated psychiatric care both within and between health systems.

Effect of Cold Atmospheric Plasma Therapy vs Standard Therapy Placebo on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.

Importance: Diabetic foot ulcers are a common complication of diabetes and require specialized treatment. Cold atmospheric plasma (CAP) has been associated with benefits in wound infection and healing in previous smaller series of case reports. Yet the effect of CAP compared with standard care therapy in wound healing in diabetic foot ulcers remains to be studied. Objective: To determine whether the application of CAP accelerates wound healing in diabetic foot ulcers compared with standard care therapy. Design, Setting, and Participants: A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted at 2 clinics with recruitment from August 17, 2016, to April 20, 2019. Patients were scheduled to remain in follow-up until April 30, 2024. Patients with diabetes and diabetic foot ulcers described using the combined Wagner-Armstrong classification of 1B or 2B (superficial or infected diabetic foot ulcers extending to tendon) were eligible. A patient could participate with 1 or more wounds in both groups in both intervention and control groups. Wounds were randomized separately, allowing a participant to be treated several times within the study following a 2 × 2 × 2 randomization strata considering sex, smoking status, and age (≤68 years and >68 years). Interventions: Standard care treatment with 8 applications of either CAP generated from argon gas in an atmospheric pressure plasma jet or 8 applications of placebo treatment in a patient-blinded manner. Main Outcomes and Measures: Primary end points were reduction in wound size, clinical infection, and microbial load compared with treatment start. Secondary end points were time to relevant wound reduction (>10%), reduction of infection, parameters of patient's well-being, and treatment-associated adverse events. Results: Of 65 diabetic foot ulcer wounds from 45 patients assessed for study, 33 wounds from 29 patients were randomized to CAP and 32 wounds from 28 to placebo, with 62 wounds from 43 patients (31 wounds per group) included for final evaluation (mean [SD] age, 68.5 [9.1] years for full sample). Four patients with 5 wounds of 31 (16.1%) wounds in the CAP group and 3 patients with 4 wounds of 31 (13%) wounds in the placebo group were active smokers. CAP therapy yielded a significant increase in wound healing, both in total mean (SD) area reduction (CAP vs placebo relative units, -26.31 [11.72]; P = .03) and mean (SD) time to relevant wound area reduction (CAP vs placebo relative units, 10% from baseline, 1.60 [0.58]; P = .009). Reduction of infection and microbial load was not significantly different between CAP and placebo. No therapy-related adverse events occurred during therapy; patient's perceptions during therapy were comparable. Conclusions and Relevance: In this randomized clinical trial, CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection. Trial Registration: ClinicalTrials.gov Identifier: NCT04205942.