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Digital technologies for type 2 diabetes mellitus (T2DM) care hold great potential to improve patients' health in the long term. Only a subset of telemedicine offerings are digital interventions that meet the criteria for prescribable digitale Gesundheitsanwendung (digital health apps; DiGAs) in Germany. Digital treatments further provide vast amounts of patient data that are important to generate evidence. This systematic review aims to analyze the efficacy of multimodal digital therapies that mainly meet the DiGA criteria for patients with T2DM and to elicit the potential of such therapies. This includes evidence from randomized controlled trials (RCTs) as well as from real-world data. The outcome of interest was a reduction in glycated hemoglobin (hemoglobin A [HbA ]; long-term blood glucose measurements). A systematic literature search was conducted in the literature bases PubMed, LIVIVO, and Cochrane, based on the predefined PICO (Population; Intervention; Control; Outcome) scheme. Identified studies were assessed for risk of bias, pragmatism, and overall quality of evidence. Meta-analyses were conducted for between group differences using RCTs only, and for within-group differences using RCTs and non-RCTs, to examine the effect of the interventions on HbA . In total, 795 records were identified, of which 24 were eligible for this systematic review and 23 studies were eligible for the meta-analysis. The results of the meta-analyses showed significant and clinically relevant reductions in HbA in patients with T2DM. Regarding the between-group difference for HbA reduction, the pooled effect of the RCTs showed a reduction of -0.36% (95% CI -0.59% to -0.14%; P<.001), favoring app-based interventions. The average mean within-group reduction in HbA was -0.79 (95% CI -1.02 to -0.55), with no significant difference between RCTs (-0.69, 95% CI -1.13 to -0.24) and non-RCTs (-0.87, 95% CI -1.16 to -0.57; P<.01, differences between RCTs and RCTs P=.44). A pragmatism rating showed that both study types were on average (very) pragmatic, that is, close to usual care. However, the overall quality of evidence was low to very low. This systematic review shows that digital therapies that mainly meet the DiGA criteria can effectively improve HbA in patients with T2DM. The integration of digital health care into usual care holds great potential and should be considered as a complementary option to usual care in the future. PROSPERO CRD42023440203; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=440203.

Digital health interventions, such as mobile diabetes apps, are aimed at supporting glycemic control. Real-world data (RWD) provide valuable insights into their long-term effectiveness beyond the controlled conditions of randomized trials. This study evaluates the effectiveness of the mobile diabetes app ESYSTA in improving glycemic control using real-world evidence. A retrospective analysis of 475 users was conducted to assess HbA1c changes after 6 months of usage and also long-term usage (12 and 15 months). A linear mixed model was used to adjust for confounding factors. After 6 months, ESYSTA users achieved a significant HbA1c reduction of -0.59 (-0.70; -0.48) percentage points compared to baseline, which was maintained for up to 15 months. Users with higher baseline HbA1c showed greater reductions. Seventy-five percent of users tracked their blood glucose values consistently during the whole observation period. These real-world evidence findings demonstrate the effectiveness of a mobile diabetes app in improving glycemic control over an extended period. While statistical adjustments addressed potential biases, missing data remain a challenge. Further research, including controlled studies, is needed to confirm these real-world results and further explore the underlying mechanisms of sustained HbA1c improvement.

Based on pharmacological studies, corticotropin-releasing hormone (CRH) and its receptors play a leading role in the inhibition of the hypothalamic-pituitary-gonadal (HPG) axis during acute stress. To further study the effects of CRH receptor signaling on the HPG axis, we generated and/or employed male mice lacking CRH receptor type 1 (CRHR1) or type 2 (CRHR2) in gonadotropin-releasing hormone neurons, GABAergic neurons, or in all central neurons and glia. The deletion of CRHRs revealed a preserved decrease of plasma luteinizing hormone (LH) in response to either psychophysical or immunological stress. However, under basal conditions, central infusion of CRH into mice lacking CRHR1 in all central neurons and glia, or application of CRH to pituitary cultures from mice lacking CRHR2, failed to suppress LH release, unlike in controls. Our results, taken together with those of the earlier pharmacological studies, suggest that inhibition of the male HPG axis during acute stress is mediated by other factors along with CRH, and that CRH suppresses the HPG axis at the central and pituitary levels via CRHR1 and CRHR2, respectively.

Digital applications have the potential to enhance diabetes management, particularly in patients treated with insulin. This study aims to evaluate the impact of a digital application on self-management (ESYSTA, Germany), expressed in a change in HbA1c levels, in people with diabetes treated with insulin. A randomized controlled, multicentric trial was conducted in 204 people with diabetes (60% type 2 diabetes) treated with insulin to assess the efficacy of ESYSTA. Participants were randomly assigned to either the intervention group (IG) using ESYSTA in addition to the German standard of Care (SoC) according to the German disease management programs (DMP) for 6 months or a control group (CG) receiving SoC only. The primary endpoint was the change in HbA1c levels. Secondary endpoints included well-being and diabetes-related distress. A clinically relevant reduction in HbA1c levels of on average -0.48% points (-0.66; -0.29) was observed in the IG after 6 months. Compared to the CG, this reduction was more pronounced, especially in the per-protocol sample [mean difference, -0.28% points; 95% CI (-0.54; -0.02)]. Improvements in the IG in further secondary endpoints, such as well-being or diabetes-related distress, indicate enhanced overall glycemic control and patient satisfaction in the IG. The use of ESYSTA improved HbA1c levels and other secondary outcomes in people with diabetes who are treated with insulin in comparison with German SoC in the context of DMP. These findings support the integration of digital tools in routine diabetes care to optimize patient outcomes. https://drks.de/search/de/trial/DRKS00025996, identifier DRKS00025996.

Background Nocturnal cough and wheeze are important symptoms when diagnosing any respiratory disease in a child, but objective measurements of these symptoms are not performed. Methods The aim of our study was to analyze the use of an automated detection system to assess breath sounds objectively in comparison to cough and wheeze questionnaires and to evaluate its feasibility in clinical practice. Results Forty-nine recordings of thirty-nine children were processed (asthma n  = 13; cystic fibrosis n  = 2; pneumonia n  = 5; suspicion of habit cough n  = 7; prolonged, recurrent or chronic cough n  = 13), and cough and asthma scores were compared to the objective nocturnal recordings. Time for audio-validation of recordings took between 2 and 40 min (mean: 14.22 min, (SD): 10.72). Accuracy of the automated measurement was higher for cough than for wheezing sounds. Nocturnal cough readings but not wheeze readings correlated with some of the corresponding scores. Conclusion To our knowledge this is the first study using a new device to assess nocturnal cough and obstructive breath sounds objectively in children with a wide variety of respiratory diseases. The assessment proved user friendly. We obtained additional information on nighttime symptoms, which would otherwise have remained obscure. Further studies to assess possible diagnostic and therapeutic benefits of this device are needed.

This multi-center, parallel-group randomized controlled trial evaluated the app-based intervention , developed by Vision2b GmbH in Germany, for people with type 2 diabetes compared to a placebo app. A total of 153 participants were randomized in a 1:1 ratio to either intervention or control group, with allocation concealment ensured by a minimization procedure. After six months, participants using achieved a statistically significant reduction in HbA1c levels by 0.82 percentage points (95% confidence interval: -1.20, -0.48,  = 0.003). This reduction was greater than in the control group (mean difference: 0.24 percentage points, 95% confidence interval: -0.44, 0.09). users further experienced greater weight loss, lower diabetes-related distress, and reduced depression severity. Adherence to the app was high, with more than 75% of participants using throughout the study period. These findings indicate that the digital approach can meaningfully improve both glycemic control and psychological well-being in people with type 2 diabetes, supporting its potential integration into routine care. https://www.evamebix.de, identifier DRKS00025719, DRKS00032395.

Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

Related Article Correction of: https://cardio.jmir.org/2024/1/e57960

Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 ( Aqp4 –/– ) or lacking the endfoot pool of AQP4 ( Snta1 –/– ). We confirm that Aqp4 –/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1 –/– mice have reduced clearance only for the 500 kDa [ 3 H]dextran, but not 0.18 kDa [ 3 H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [ 3 H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules.

Digital interventions are promising additions for both usual care and rehabilitation. Evidence and studies for the latter, however, are still rare. The aim of the study was to examine the app/web-based patient education program called \"mebix\" (previously called \"Vision 2 - Gesundes Herz\") regarding its effectiveness in relation to the parameters of disease-specific quality of life (HeartQoL), cardiovascular risk profile (Cardiovascular Risk Management [CARRISMA]), and prognostic estimation of early retirement (Screening instrument work and occupation [SIBAR]) in 190 participants from a cardiological rehabilitation clinic. To evaluate mebix, 354 patients from the Roderbirken Clinic of the German Pension Insurance Rhineland (Germany) with a coronary heart diesase were recruited and randomized either to the intervention group (using mebix postrehabiliation for up to 12 months) or the control group (receiving standard care). The data collection took place at the end of inpatient rehabilitation (t0), as well as 6 months (t1) and 12 months (t2) after the end of rehabilitation. Analyses of variance are used to assess the overall significance of difference in outcome parameters between groups and over time. The primary endpoint of disease-related quality of life shows a significant improvement of 7.35 points over the course of the intervention that is also more pronounced in the intervention group. Similarly, the 10-year risk of cardiovascular death and myocardial infarction showed significant improvements in the cardiovascular risk profile over time and between groups, indicating better results in the intervention group (ie, a reduction of -1.59 and -5.03, respectively). Secondary outcomes like the body weight and cholesterol levels were significantly reduced in the intervention group, also in comparison with the control group. In addition, the SIBAR was significantly lower/better at the end of the observation period than at the beginning of the observation for both groups. Overall, the digital training program represents an effective follow-up offer after rehabilitation that could be incorporated into standard care to further improve disease-related quality of life and cardiovascular risk profiles.