Corrigendum: Integration of digital health applications into the German healthcare system: development of "The DiGA-Care Path".

[This corrects the article DOI: 10.3389/frhs.2024.1372522.].

Integration of digital health applications into the German healthcare system: development of "The DiGA-Care Path".

Introduction: Since 2019 people who have insured in the German statutory health insurance are entitled to use certified apps called the Digitale Gesundheitsanwendungen [Digital Health Applications (DiGAs)]. The prerequisite for this is that an app certified as DiGA and suitable for their diagnosis exists. The DiGA can then either be prescribed by a physician or psychotherapist or requested by the patient from the statutory health insurance fund. Given the novelty of this type of healthcare, the implementation of a DiGA should be closely monitored to identify potential weaknesses and achieve quality improvements. To enable an analysis of the supply of DiGAs step-by-step, we aimed to create the DiGA-Care Path. Methods: We conducted three steps to create the DiGA-Care Path. First, a knowledge base was created based on a structured literature research matched with knowledge gathered from the superordinate research project "QuaSiApps" funded by the German Federal Joint Committee. Second, we aimed to create an "ideal-typical" DiGA-Care Path using a flowchart. Third, based on the first path, a final path was developed using the graphical modeling language "Event-Driven Process Chain." Results: The DiGA-Care Path was developed to depict the supply of DiGAs in Germany. The final path is constituted by a "main path" as well as a corresponding "sub-path". While the "main path" focuses more on the supply environment in which a DiGA is used, the "sub-path" depicts the supply delivered by the DiGA itself. Besides the process itself, the paths include relevant actors to indicate responsibilities for individual process steps. Discussion: The DiGA-Care Path helps to analyze the current supply of DiGAs step-by-step. Thereby, each step can be investigated in detail to identify problems and to detect further steps where quality improvements can be enabled. Depending on the perspective, focused either on the supply environment, or the supply delivered by the DiGA itself, the "main path" or the "sub-path" can be used, respectively. Besides the potential of the DiGA-Care Path to improve the current supply of DiGAs, it can help as an orientation for international policymakers or further stakeholders either to develop their own integration of apps into healthcare systems or for international manufacturers to consider entering the German market.

Assessment of innovative living and care arrangements for persons with dementia: a systematic review.

BACKGROUND: Alternative forms of housing for persons with dementia have been developed in recent decades. These concepts offer small groups of residents familiar settings combined with efforts to provide normal daily life. The aim of this systematic review is to collate and analyze these more innovative forms of housing regarding residents' quality of life, behavioral aspects, as well as functional, cognitive and emotional aspects. METHODS: Searches were conducted in PubMed, EMBASE and PsycInfo in November 2020. Studies comparing traditional and more innovative living environments for persons with dementia were eligible. Concepts are described based on the results of additional searches. Risk of bias of included studies was assessed using checklists from the Joanna Briggs Institute. RESULTS: A total of 21 studies corresponding to 11 different concepts were included, namely Green Houses (USA), Group Living (Sweden), Cantou (France), Group Homes (Japan), Small-scale Group Living (Austria), Special Care Facilities (Canada), Shared-housing Arrangements (Germany), Residential Groups (Germany), Residential Care Centers / Woodside Places (USA/Canada), Small-scale Living (Netherlands/ Belgium), and Green Care Farms (Netherlands). The concepts are broadly similar in terms of care concepts, but partly differ in group sizes, staff qualifications and responsibilities. Several studies indicate that innovative forms of housing may encourage social behavior, preserve activity performance and/or positively influence emotional status compared to more traditional settings, while other studies fail to demonstrate these effects. Some studies also show increased behavioral and psychological symptoms of dementia (BPSD) in residents who live in more innovative housing concepts. The effect on cognition remains indistinct. DISCUSSION: The positive effects may be attributable to the inherent characteristics, including small group sizes, a stimulating design, and altered staff roles and responsibilities. Arguably, some of these characteristics might also be the reason for increased BPSD. Studies had variable methodological quality and results have to be considered with caution. Future research should examine these effects more closely and should investigate populations' preferences with regards to housing in the event of dementia.

A glycopyrronium bromide 1% cream for topical treatment of primary axillary hyperhidrosis: efficacy and safety results from a phase IIIa randomized controlled trial.

BACKGROUND: Effective topical treatment options for patients with primary axillary hyperhidrosis (PAHH) are limited. A phase I trial showed promising results regarding the efficacy and safety of a topical cream containing glycopyrronium bromide (GPB). OBJECTIVES: To assess the efficacy, safety and tolerability of a 4-week topical treatment of GPB 1% cream in patients with PAHH vs. placebo. METHODS: In total, 171 patients (84 receiving placebo; 87 receiving GPB 1%) with PAHH were included in the 4-week, multicentre, randomized, double-blind, placebo-controlled phase IIIa part of the pivotal study. Sweat production was measured by gravimetry. Patients rated the impact of disease with the Hyperhidrosis Disease Severity Scale (HDSS) and Hyperhidrosis Quality of Life Index (HidroQoL© ). RESULTS: Absolute change in sweat production from baseline to day 29 in logarithmic values was significantly larger in the GPB 1% group compared with the placebo group (P = 0·004). The improvement in HidroQoL exceeded the minimal clinically important difference of 4. The proportion of responders was twofold higher for sweat reduction (-197·08 mg GPB 1% vs. -83·49 mg placebo), HDSS (23% GPB 1% vs. 12% placebo) and HidroQoL (60% GPB 1% vs. 26% placebo). Treatment was safe: most treatment-emergent adverse effects were mild or moderate, and transient. Local tolerability was very good, with 9% of patients having only mild or moderate application-site reactions. The most reported adverse drug reaction was dry mouth (16%), an expected anticholinergic effect of the treatment. CONCLUSIONS: GPB 1% cream may provide an effective new treatment option exhibiting a good safety profile for patients with PAHH. The long-term open-label part (phase IIIb) is ongoing.

Hyperhidrosis Quality of Life Index (HidroQoL©): further validation and clinical application in patients with axillary hyperhidrosis using data from a phase III randomized controlled trial.

BACKGROUND: The Hyperhidrosis Quality of Life Index (HidroQoL©) is a validated patient-reported outcome measure capturing the quality of life of people affected by hyperhidrosis. OBJECTIVES: We aimed to extend the validity evidence to physician-confirmed diagnosis of primary axillary hyperhidrosis. METHODS: Data from a phase III randomized placebo-controlled clinical trial were used (n = 171). Confirmatory factor analysis was carried out to confirm the a priori two-factor structure of the HidroQoL. Internal consistency was assessed using Cronbach's α. Intraclass correlation coefficients (ICCs) were calculated to evaluate test-retest reliability after days -7 to -4. Convergent validity was assessed using correlations with the Dermatology Life Quality Index (DLQI), the Hyperhidrosis Disease Severity Scale (HDSS) and gravimetric sweat production. Known groups were analysed to evaluate discriminative validity. Responsiveness after 29 days was assessed and minimal important difference (MID) values were calculated using both anchor- and distribution-based approaches. All analyses were carried out for total HidroQoL and its two domains. RESULTS: The two-factor structure of the HidroQoL was confirmed. Internal consistency and test-retest reliability were strong (Cronbach's α 0·81-0·90; ICCs 0·89-0·93). Correlations with other outcome measures were in line with a priori hypotheses. The HidroQoL discriminated between different severity groups (P ≤ 0·001) and showed sensitivity to change towards improvement (P < 0·001). An MID value of 4 is proposed for the total scale. CONCLUSIONS: This study supports excellent measurement properties including clinical applicability of the HidroQoL in primary axillary hyperhidrosis and suggests a MID of 4 be applied to clinical trial data.

Double blinded, vehicle controlled, crossover study on the efficacy of a topical endocannabinoid membrane transporter inhibitor in atopic Beagles.

The endocannabinoid system is important for skin homeostasis and alterations are linked to inflammatory diseases like atopic dermatitis (AD). Importantly, activation of cannabinoid receptor CB2 decreases pruritus and inflammation in mouse models. Reduction of inactivation of endogenous cannabinoids could, therefore, be a therapeutic option for AD. Dogs spontaneously develop AD, which closely mimics the human disease making them suitable to test new therapies. Our study aimed to test the effects of a topical endocannabinoid membrane transporter inhibitor (WOL067-531, 1% gel) on pruritus and dermatitis in a canine model of AD. Nineteen Beagles allergic to dust mites (DM) were randomized to receive either active ingredient or vehicle on inguinal area while challenged epicutaneously with DM twice weekly for 28 days. Treatment was administered twice daily and started after three challenges (day 8). Dermatitis and pruritus were scored weekly by personnel blinded to treatment allocation. Dermatitis was scored using a validated scoring system and pruritus was scored using camera recordings. After a 4-week washout, dogs were crossed over and the study was repeated. On days 15 and 22, dermatitis scores were significantly increased after DM challenge in the vehicle group (16.34, p = 0.0089 and 7.42, p = 0.04845, respectively) but not in the active ingredient group (p = 0.3177 and p = 0.3190, respectively). Significant decrease on pruritus both on inguinal area and overall (p = 0.048 and p = 0.032, respectively) occurred in the active ingredient group. No adverse effects were noted. In conclusion, the newly developed topical endocannabinoid membrane transporter inhibitor (WOL067-531) minimized allergic flares and pruritus in a canine model of AD.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water-in-oil emulsion in aged skin.

BACKGROUND: Increased skin-surface pH is an important host-related factor for deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether restoration of skin pH through topical application of a water-in-oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. METHODS: The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of barrier function in aged skin. The long-term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin-surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. RESULTS: The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin-surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. CONCLUSIONS: Exogenous acidification through topical application of a water-in-oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.

A bio-inspired real-time capable artificial lateral line system for freestream flow measurements.

To enhance today's artificial flow sensing capabilities in aerial and underwater robotics, future robots could be equipped with a large number of miniaturized sensors distributed over the surface to provide high resolution measurement of the surrounding fluid flow. In this work we show a linear array of closely separated bio-inspired micro-electro-mechanical flow sensors whose sensing mechanism is based on a piezoresistive strain-gauge along a stress-driven cantilever beam, mimicking the biological superficial neuromasts found in the lateral line organ of fishes. Aiming to improve state-of-the-art flow sensing capability in autonomously flying and swimming robots, our artificial lateral line system was designed and developed to feature multi-parameter freestream flow measurements which provide information about (1) local flow velocities as measured by the signal amplitudes from the individual cantilevers as well as (2) propagation velocity, (3) linear forward/backward direction along the cantilever beam orientation and (4) periodicity of pulses or pulse trains determined by cross-correlating sensor signals. A real-time capable cross-correlation procedure was developed which makes it possible to extract freestream flow direction and velocity information from flow fluctuations. The computed flow velocities deviate from a commercial system by 0.09 m s(-1) at 0.5 m s(-1) and 0.15 m s(-1) at 1.0 m s(-1) flow velocity for a sampling rate of 240 Hz and a sensor distance of 38 mm. Although experiments were performed in air, the presented flow sensing system can be applied to underwater vehicles as well, once the sensors are embedded in a waterproof micro-electro-mechanical systems package.

The impact of 10% α-hydroxy acid emulsion on skin pH.

BACKGROUND/AIMS: The effects of a 10% α-hydroxy acid (AHA) oil/water (O/W) emulsion on the pH of human skin surface (pH(ss)) and stratum corneum (SC; pH(sc)) were evaluated in vivo. METHODS: The AHA O/W emulsion was applied to an area on the volar forearm of male volunteers (n = 12), and then wiped off after 10 min. Prior to application and over the following 3 h, the pH(ss) was measured. We used glass electrode measurements and time domain dual lifetime referencing (tdDLR) with luminescent sensor foils. In another experiment (n = 5), the impact of the AHA O/W emulsion on the pH(sc) gradient was measured by tape stripping of the SC of the volar forearm after application of the AHA O/W emulsion. RESULTS: Compared with pH(ss) values prior to treatment [5.2 ± 1.7 (tdDLR) or 4.8 ± 0.5 (electrode)], the pH(ss) was significantly reduced 10 min after application [4.0 ± 0.3 (tdDLR) or 4.1 ± 0.1 (electrode)] and the pH(ss) remained significantly reduced over the measurement period of 3 h [after 3 h: 4.4 ± 0.2 (tdDLR) or 4.5 ± 0.3 (electrode)]. The AHA O/W emulsion significantly reduced the pH(sc) even down to deep layers of the SC. CONCLUSION: After a 10-min application time, the 10% AHA O/W emulsion reduces the pH(ss) (for at least 3 h) and pH(sc) in deep layers of the SC.

Clinical safety and efficacy of a novel thermoreversible polyhexanide-preserved wound covering gel.

BACKGROUND: An ideal topical formulation for wound therapy does not exist. The aim of this study was to develop a novel improved therapeutic option for the treatment of acute and chronic wounds. METHODS: A transparent wound gel which is in a liquid state below and in a gel state at or above room temperature was developed. Forty-four patients were included in this open randomized controlled single-center study. Flammazine served as control in the treatment of skin graft donor sites. Wounds were assessed for time of dressing change and overall satisfaction of patients and health care providers. The data were analyzed using the nonparametric Mann-Whitney test. RESULTS: The wound gel proved to be superior in comparison with Flammazine with respect to wound assessment (p = 0.002), staining (p = 0.007), leaking (p = 0.032) and smell (p = 0.034). Flammazine showed favorable results regarding the parameters dehydration of the dressings (p = 0.012) and wound adherence (p = 0.005). The evaluation of the overall dressing change process showed no significant differences. CONCLUSION: The thermoreversible wound gel containing polyhexanide allows for good handling and wound assessment. This study demonstrated a high satisfaction level of patient and health care providers, and the wound gel proved an effective alternative to commonly used treatments.

Evaluation of a novel polihexanide-preserved wound covering gel on dermal wound healing.

OBJECTIVE: Daily wound assessment, including dressing changes and the removal of old ointments causes discomfort for the patient. We therefore developed a new thermoreversible and transparent gel formulation that allows for filling wounds of different shapes and depths. The aim of the study was to investigate the effect of a wound covering gel on wound healing and the skin's microcirculation. MATERIALS AND METHODS: Investigations were carried out in a standardized and reproducible wound model (hairless mice SKH1/hr, n = 30). Three groups were studied by intravital fluorescence microscopy: treatment with polihexanide-preserved wound covering gel, a formulation containing 3% povidone (PVP)-iodine, and physiological saline for control. Microcirculatory standard parameters were analysed. RESULTS: The non-perfused area vanished within 14 days due to angiogenesis. The venular diameter, oedema formation and functional capillary density showed no significant differences between the three groups. CONCLUSION: The use of the newly developed wound covering gel has no toxic effects on microcirculation and angiogenesis and reveals no significant differences in the overall assessment of microcirculation compared to the control group and the well-established PVP-iodine. The transparent antibacterial wound covering gel allows for direct wound assessment. Due to its thermoreversible gel formulation it enables good wound contact and easy handling.

The alpha-melanocyte stimulating hormone-related tripeptide K(D)PT stimulates human hair follicle pigmentation in situ under proinflammatory conditions.

BACKGROUND: Alpha-melanocyte stimulating hormone (alpha-MSH) is a well-tolerated immunomodulator with cytoprotective and anti-inflammatory effects that is known to stimulate melanogenesis and proliferation of follicular melanocytes. As human hair follicles (HFs) locally synthesize alpha-MSH, pharmacologically more easily handled alpha-MSH-related tripeptides, such as K(D)PT, may imitate this endogenous regulation, and may show a favourable side-effect profile on clinical use. OBJECTIVES: To investigate the effect of the synthetic, alpha-MSH-related peptide K(D)PT [which is identical to interleukin (IL)-1beta(193-195)] on melanogenesis in human anagen HFs, under normal and proinflammatory growth conditions. METHODS: Normal human anagen VI scalp HFs were microdissected and organ cultured with different concentrations of K(D)PT with or without coadministration of a proinflammatory, catagen-inducing stimulus, interferon (INF)-gamma. Masson-Fontana histochemistry and NKI/beteb immunohistochemistry were employed to assess changes in the degree of human HF pigmentation and melanocyte dendricity. RESULTS: As confirmed by quantitative (immuno-)histomorphometry, compared with controls, K(D)PT alone did not affect human HF pigmentation in organ culture. However, in the presence of a strong, prototypic proinflammatory stimulus (IFN-gamma), K(D)PT significantly stimulated HF melanin content and melanocyte dendrite formation in situ. CONCLUSIONS: The IL-1beta- and alpha-MSH-related tripeptide, K(D)PT, displays interesting hair pigmentation-stimulatory activities under proinflammatory conditions. These might become exploitable for innovative antigreying strategies, notably in postinflammatory poliosis (regrowth of white hair, e.g. during recovery from alopecia areata), where no effective clinical therapy is yet available.

Intravaginally applied metronidazole is as effective as orally applied in the treatment of bacterial vaginosis, but exhibits significantly less side effects.

OBJECTIVE: Metronidazole is the drug of choice for the treatment of bacterial vaginosis (BV). However, so far the oral administration has not been clinically compared to the intravaginal application regarding efficacy, side effects and patient satisfaction in a scientific sound fashion. STUDY DESIGN: Therefore, this randomized, double-blind, placebo-controlled clinical trial was designed to demonstrate non-inferiority of short-term intravaginal (i.vag.) application of metronidazole (2x 1000 mg pessaries 24h apart) vs. a single oral dose (p.o.) of metronidazole (1 x 2000 mg tablets) in 263 patients with BV (double-dummy design). The follow-up period was 12 weeks. In addition, the number and the type of adverse events induced by the two regimens were compared, assuming better tolerability of the intravaginal application. RESULTS: Following the diagnosis of BV a total of 129 women (mean age 36.2 years) was orally treated with a single dose of 2g metronidazole whereas a total of 134 patients (mean age 35.5 years) was treated intravaginally with 1g metronidazole each day on two consecutive days and included in the per-protocol analysis. Non-inferiority of i.vag. application compared to p.o. administration was statistically significant regarding efficacy: Following intravaginal application the cure rate, assessed on day 8 after starting of the treatment, was 92.5% as compared to 89.9% after oral administration. Nausea was the most common adverse event reported in 10.2% i.vag. vs. 30.4% p.o. of all cases (p<0.001), abdominal pain in 16.8% i.vag. vs. 31.9% p.o. (p<0.01), a "metallic taste" in 8.8% i.vag. vs. 17.9% p.o. (p<0.05). Women treated i.vag. were highly satisfied with the treatment and more content as compared to the women treated p.o. with metronidazole (p<0.05, intent-to-treat analysis). CONCLUSION: In this clinical trial the intravaginal application was as effective as the oral administration of metronidazole in treating BV. However, significantly less adverse events were reported after short-term intravaginal as compared to oral application (p=0.023) and probably led to a better patient compliance.

Determination of the antibacterial efficacy of a new porphyrin-based photosensitizer against MRSA ex vivo.

Following extensive in vitro screening of new photosensitizers the purpose of the present study was to examine penetration as well as antibacterial efficacy of a lead photosensitizer against MRSA using an ex vivo porcine skin model. Two different applications were performed: (i) preincubation of bacteria in solution with a porphyrin-based photosensitizer XF73 and subsequent application on the ex vivo porcine skin; (ii) application of pure bacteria on the explants followed by an incubation with XF73 in a water-ethanol formulation for up to 60 min under occlusion. The localisation of XF73 was restricted to the stratum corneum. Different concentrations (0-10 microM) of XF73 and different incubation times (5-60 min) were used to determine phototoxicity against methicillin-resistant and methicillin-sensitive S. aureus, which was applied on the explants. Preincubation of S. aureus with 0.1 microM XF73 in solution prior to the application of these XF73-incubated bacteria on the skin demonstrates a higher efficacy (>3 log10) after irradiation. Antibacterial photodynamic inactivation resulted in a approximately 1 log10 (0.1 microM)-3.64+/-0.035 (10 microM) log10 growth reduction independently of the antibiotic resistance pattern of used S. aureus strains. Irradiation of applied bacteria without photosensitizer incubation did not show any marked decrease (<1 log10) of bacteria cell number, indicating a significant phototoxicity of the XF73. Histological evaluations of untreated and treated skin areas upon irradiation within 24 h showed no significant degree of necrosis or apoptosis determined by TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates that this XF73 porphyrin-based photosensitizer had concentration-dependent differences in killing efficacy of MRSA in comparison to skin cells using an ex vivo porcine skin model. The results described here imply that topical delivery of XF73 may be considered as a possible treatment in patients with superficial infections of the skin.

[Therapy of atopic dermatitis]. / Therapie des atopischen Ekzems.

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.

[Antibacterial photodynamic therapy. A new treatment for superficial bacterial infections?]. / Antibakterielle photodynamische Therapie. Ein neues Verfahren zur Behandlung von oberflächlichen bakteriellen Infektionen?

The basis of "antibacterial photodynamic therapy" involves the killing of bacteria by reactive oxygen species in the presence of a photosensitizer and light. Possible dermatologic indications include inactivation of bacteria in skin and wound infections and reduction in density of nosocomial multi-resistant infections. The chief advantage of antibacterial photodynamic therapy is that regardless of the resistance pattern of a bacteria, inactivation can be achieved, analogous to the use of antiseptics. The aim of the present review is to describe the physicochemical and biological mechanisms of antibacterial photodynamic therapy as well as possible clinical indications in dermatology.