Telephone Health Coaching and Remote Exercise Monitoring (TeGeCoach) in Peripheral Arterial Occlusive Disease.

BACKGROUND: Supervised exercise programs are used to treat intermittent claudication (IC). Home-based exercise programs have been developed to lower barriers to participation. We studied the effects of one such exercise program (TeGeCoach) on self-reported walking ability in patients with IC. METHODS: In a pragmatic multicenter randomized controlled trial (registration number NCT03496948), 1982 patients with symp - tomatic IC insured by one of three German statutory health insurance funds received either telephone health coaching with remote exercise monitoring (TeGeCoach; n = 994) or routine care (n = 988). The primary outcome was the change in Walking Impairment Questionnaire (WIQ) scores after 12 and 24 months in the intention-to-treat population. The secondary outcomes were healthrelated quality of life, symptoms of depression or anxiety, health competence, patient activation, alcohol use, and nicotine depen - dence. RESULTS: There was a significant group difference in WIQ score in favor of TeGeCoach (p < 0.0001), amounting to 6.30 points at 12 months (Bonferroni-corrected 95% CI [4.02; 8.59], Cohen's d = 0.26) and 4.55 points at 24 months ([2.20; 6.91], d = 0.19). Some of the secondary outcomes also showed positive results in favor of TeGeCoach at 12 months with small effect sizes (d ≥ 0.20), including physical health-related quality of life and patient activation. The average daily step count was not higher in the TeGeCoach group. CONCLUSION: Significant improvements regarding symptom burden demonstrate the benefit of a home-based exercise program and thus expand the opportunities for guideline-oriented treatment of IC. Future studies should additionally address the effect of home-based exercise programs on clinical variables by means of, for example, the 6-minute walk test.

TIMP-2 and IGFBP7 in human kidney biopsies in renal disease.

Background: Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are markers of tubular stress and urinary [TIMP-2]*[IGFBP7] is an established biomarker for risk assessment of acute kidney injury. There are no studies of expression profiles or localization of these markers in human renal tissue with confirmed renal disease. Methods: We analysed 37 kidney biopsies of patients with renal disease and 10 non-diseased control biopsies for TIMP-2 and IGFBP7 expression using immunohistochemistry. Changes in glomerular morphology were evaluated by a semi-quantitative glomerulosclerosis score (GSI) and tubular interstitial changes were graded by the tubular injury score (TSI) using periodic acid-Schiff-stained paraffin sections. Interstitial fibrosis and tubular atrophy (IF/TA) were graded according to the Banff classification. Urinary [TIMP-2]*[IGFBP7] was collected at the time of biopsy. Results: TIMP-2 and IGFBP7 had significantly greater expression in kidney biopsies from patients with renal disease compared with control tissue, especially in the tubular compartment. Here, IGFBP7 was detected in proximal and distal tubules while TIMP-2 was predominantly localized in the collecting ducts. Renal injury significantly correlated with staining intensity for TIMP-2 and IGFBP7: GSI weakly correlated with glomerular TIMP-2 (r = 0.36) and IGFBP7 (r = 0.35) and TSI correlated with tubular TIMP-2 (r = 0.41) and IGFBP7 (r = 0.43). Urinary [TIMP-2]*[IGFBP7] correlated weakly with the histopathological damage score but not with glomerular and tubular expression. Conclusion: Our findings underline the role of TIMP-2/IGFBP7 as an unspecific marker of renal injury that is already in use for early detection of acute kidney injury.

The effect of telephone health coaching and remote exercise monitoring for peripheral artery disease (TeGeCoach) on health care cost and utilization: results of a randomized controlled trial.

BACKGROUND: Peripheral artery disease (PAD) is the third most prevalent atherosclerotic cardiovascular disease. In 2016, costs per patient associated with PAD exceeded even the health-economic burden of coronary heart disease. Although affecting over 200 million people worldwide, a clear consensus on the most beneficial components to be included in home-based exercise programs for patients with peripheral artery disease is lacking. The aim of the study was to examine the health care use and costs caused by the 12-month patient-centered 'Telephone Health Coaching and Remote Exercise Monitoring for Peripheral Artery Disease' (TeGeCoach) program in a randomized controlled trial. METHODS: This is a two-arm, parallel-group, open-label, pragmatic, randomized, controlled clinical trial (TeGeCoach) at three German statutory health insurance funds with follow-up assessments after 12 and 24-months. Study outcomes were medication use (daily defined doses), days in hospital, sick pay days and health care costs, from the health insurers' perspective. Claims data from the participating health insurers were used for analyses. The main analytic approach was an intention-to-treat (ITT) analysis. Other approaches (modified ITT, per protocol, and as treated) were executed additionally as sensitivity analysis. Random-effects regression models were calculated to determine difference-in-difference (DD) estimators for the first- and the second year of follow-up. Additionally, existing differences at baseline between both groups were treated with entropy balancing to check for the stability of the calculated estimators. RESULTS: One thousand six hundred eighty-five patients (Intervention group (IG) = 806; Control group (CG) = 879) were finally included in ITT analyses. The analyses showed non-significant effects of the intervention on savings (first year: - 352€; second year: - 215€). Sensitivity analyses confirmed primary results and showed even larger savings. CONCLUSION: Based on health insurance claims data, a significant reduction due to the home-based TeGeCoach program could not be found for health care use and costs in patients with PAD. Nevertheless, in all sensitivity analysis a tendency became apparent for a non-significant cost reducing effect. TRIAL REGISTRATION: NCT03496948 (www. CLINICALTRIALS: gov), initial release on 23 March 2018.

Algorithm-based detection of acute kidney injury according to full KDIGO criteria including urine output following cardiac surgery: a descriptive analysis.

BACKGROUND: Automated data analysis and processing has the potential to assist, improve and guide decision making in medical practice. However, by now it has not yet been fully integrated in a clinical setting. Herein we present the first results of applying algorithm-based detection to the diagnosis of postoperative acute kidney injury (AKI) comprising patient data from a cardiac surgical intensive care unit (ICU). METHODS: First, we generated a well-defined study population of cardiac surgical ICU patients by implementing an application programming interface (API) to extract, clean and select relevant data from the archived digital patient management system. Health records of N = 21,045 adult patients admitted to the ICU following cardiac surgery between 2012 and 2022 were analyzed. Secondly, we developed a software functionality to detect the incidence of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, including urine output. Incidence, severity, and temporal evolution of AKI were assessed. RESULTS: With the use of our automated data analyzing model the overall incidence of postoperative AKI was 65.4% (N = 13,755). Divided by stages, AKI 2 was the most frequent maximum disease stage with 30.5% of patients (stage 1 in 17.6%, stage 3 in 17.2%). We observed considerable temporal divergence between first detections and maximum AKI stages: 51% of patients developed AKI stage 2 or 3 after a previously identified lower stage. Length of ICU stay was significantly prolonged in AKI patients (8.8 vs. 6.6 days, p <  0.001) and increased for higher AKI stages up to 10.1 days on average. In terms of AKI criteria, urine output proved to be most relevant, contributing to detection in 87.3% (N = 12,004) of cases. CONCLUSION: The incidence of postoperative AKI following cardiac surgery is strikingly high with 65.4% when using full KDIGO-criteria including urine output. Automated data analysis demonstrated reliable early detection of AKI with progressive deterioration of renal function in the majority of patients, therefore allowing for potential earlier therapeutic intervention for preventing or lessening disease progression, reducing the length of ICU stay, and ultimately improving overall patient outcomes.

Enhanced Oxidative DNA-Damage in Peritoneal Dialysis Patients via the TXNIP/TRX Axis.

Peritoneal dialysis (PD) is an effective method of renal replacement therapy, providing a high level of patient autonomy. Nevertheless, the long-term use of PD is limited due to deleterious effects of PD fluids to the structure and function of the peritoneal membrane leading to loss of dialysis efficacy. PD patients show excessive oxidative stress compared to controls or chronic kidney disease (CKD) patients not on dialysis. Therefore, defense systems against detrimental events play a pivotal role in the integrity of the peritoneal membrane. The thioredoxin-interacting-protein (TXNIP)/thioredoxin (TRX) system also plays a major role in maintaining the redox homeostasis. We hypothesized that the upregulation of TXNIP negatively influences TRX activity, resulting in enhanced oxidative DNA-damage in PD patients. Therefore, we collected plasma samples and human peritoneal biopsies of healthy controls and PD patients as well. Using ELISA-analysis and immunohistochemistry, we showed that PD patients had elevated TXNIP levels compared to healthy controls. Furthermore, we demonstrated that PD patients had a reduced TRX activity, thereby leading to increased oxidative DNA-damage. Hence, targeting the TXNIP/TRX system as well as the use of oxidative stress scavengers could become promising therapeutic approaches potentially applicable in clinical practice in order to sustain and improve peritoneal membrane function.

Under-recognition of Acute Kidney Injury after Cardiac Surgery in the ICU Impedes Early Detection and Prevention.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality; therefore, prevention is important. The aim of this study was to systematically assess AKI incidence after cardiac surgery as documented in clinical routine compared to the real incidence because AKI may be under-recognized in clinical practice. Further, its postoperative management was compared to Kidney Disease: Improving Global Outcomes (KDIGO) recommendations because recognition and adequate treatment represent the fundamental cornerstone in the prevention and management of AKI. METHODS: This retrospective single-center study included n = 100 patients who underwent cardiac surgery with cardiopulmonary bypass. The coded incidence of postoperative AKI during intensive care unit stay after surgery was compared to the real AKI incidence. Furthermore, conformity of postoperative parameters with KDIGO recommendations for AKI prevention and management was reviewed. RESULTS: We found a considerable discrepancy between coded and real incidence, and conformity with KDIGO recommendations was found to be relatively low. The coded incidence was significantly lower (n = 12 vs. n = 52, p < 0.05), representing a coding rate of 23.1%. Regarding postoperative management, 90% of all patients had at least 1 episode with mean arterial pressure <65 mm Hg within the first 72 h. Furthermore, regarding other preventive parameters (avoiding hyperglycemia, stopping angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, avoiding contrast media, and nephrotoxic drugs), only 10 patients (20.8%) in the non-AKI group and in 5 (9.6%) subjects in the AKI group had none of all the above potential AKI-promoting factors. CONCLUSIONS: AKI recognition in everyday clinical routine seems to be low, especially in lower AKI stages, and the current postoperative management still offers potential for optimization. Possibly, higher AKI awareness and stricter postoperative management could already achieve significant effects in prevention and treatment of AKI.

Peritoneal Expression of SGLT-2, GLUT1, and GLUT3 in Peritoneal Dialysis Patients.

INTRODUCTION: In peritoneal dialysis (PD) patients, the peritoneal membrane is affected by glucose-based solutions used as peritoneal dialysate fluids. This exposure leads to changes of the membrane which may eventually culminate in fibrosis and method failure. In vitro or animal studies demonstrated that glucose transporters are upregulated upon exposure to these solutions. Expression studies of glucose transporters in human peritoneum have not been reported yet. METHODS: Expression of SGLT-2, GLUT1, and GLUT3 in human peritoneal biopsies was analyzed by real-time polymerase chain reaction and Western blot analysis. The localization of these glucose transporters in the peritoneum was evaluated by immunohistochemistry using a Histo-Score. RESULTS: Peritoneal biopsies of patients (healthy controls, uremic, PD, and encapsulating peritoneal sclerosis [EPS]) were analyzed. We found evidence of SGLT-2, GLUT1, and GLUT3 expression in the peritoneal membrane. Protein expression of SGLT-2 increases with PD duration and is significantly enhanced in EPS patients. All transporters were predominantly, but not exclusively, located adjacent to the vessel walls of the peritoneal membrane. CONCLUSION: Our study showed that SGLT-2, GLUT1, and GLUT3 were regularly expressed in the human peritoneum. SGLT-2 was particularly upregulated in PD patients with EPS, suggesting that this upregulation may be associated with pathological changes in the peritoneal membrane in this syndrome. Since preclinical studies in mice show that SGLT-2 inhibitors or downregulation of SGLT-2 ameliorated pathological changes in the peritoneum, SGLT-2 inhibitors may be potentially promising agents for therapy in PD patients that could reduce glucose absorption and delay functional deterioration of the peritoneal membrane in the long term.

Gender-Specific Differences of Renal Heat Tolerance in Older Adults during Heat Waves.

BACKGROUND: Heat waves are known to cause increased morbidity and mortality in susceptible populations like old and functionally impaired people. The objective of the study was to assess renal tubular stress, a predictor for development of acute kidney injury, during heat waves in Central Europe. As a marker of renal tubular stress tissue inhibitor of metalloproteinases-2 [TIMP-2]·insulin-like growth factor binding protein-7 [IGFBP7], a new FDA-cleared renal tubular stress biomarker, was used. MATERIALS AND METHODS: 68 residents from facilities of sheltered housing with urine samples collected at heat waves in 2015 and at control visits were included. Urinary [TIMP-2]·[IGFBP7] was compared between the heat waves and the control visits. Multivariate linear models were adjusted for age, frailty index, and functional comorbidity index. RESULTS: The median age was 82.0 years, 82.3% were women. The percentage of elevated levels of urinary [TIMP-2]·[IGFBP7] (>0.3 [ng/mL]2/1,000) in the total study population was higher at the heat waves than at the control visits (25.0% vs. 17.7%). The effect of the heat waves on urinary [TIMP-2]·[IGFBP7] was stronger in men than in women: The percentage of elevated levels was 75.0% in men and 14.3% in women. In the multivariate analysis, the mean urinary [TIMP-2]·[IGFBP7] was 0.48 (95% CI 0.25; 0.70) (ng/mL)2/1,000 higher in men than in women. Except gender, a number of additional variables did not show an association with urinary [TIMP-2]·[IGFBP7] at the heat waves or the control visits. CONCLUSIONS: At heat waves, urinary [TIMP-2]·[IGFBP7] was elevated and higher in men than in women. This suggests gender-specific differences in renal heat tolerance in older people.

Physician-guided, hybrid genetic testing exerts promising effects on health-related behavior without compromising quality of life.

Genetic risk analysis is increasingly in demand by participants. Hybrid genetic testing has the advantage over direct to consumer testing by involving a physician who guides the process and offers counseling after receiving the results. The objective of this study was to determine whether a structured physician moderated primary preventive, hybrid genetic risk assessment enhanced counseling program leads to improvement in lifestyle and does not impair quality of life. Risk genes for malignant, cardiovascular, coagulation, storage diseases and pharmacogenetics (> 100 genes) were tested. Screening, consultation and genetic counseling embedded in a primary/secondary prevention check-up program for executives of surrounding companies took place in a single center in Germany. Follow-up included established questionnaires for quality of life, nutrition and physical activity. Analysis included n = 244 participants. Median age at baseline was 49 years (interquartile range: 44-55), 93% were male, 3% (n = 7 of 136 responses) were smoker. Mean body mass index was 25.2 kg/m2. Follow-up response rate was 74% (n = 180), mean follow-up time was 6.8 months (standard deviation = 2.1). In 91 participants (37.8%, 91/241) at least one pathogenic variant was found, 60 thereof were clinically relevant (24.9%, 60/241). 238 participants (98%, 238/241) had > 1 pharmacogenetic variant, only 2 (0.8%, 2/241) took a correspondingly affected drug (56 participants took ≥ 1 drug/day). The energy expenditure significantly increased by ≈ 35% [median multiple of energy expenditure of 1.34 (confidence interval = 1.15-1.57, p < 0.001)] metabolic equivalents of task (MET)-min/week; participants spent on average 41 min (p < 0.001) less in sedentary activities per day and spent more time for lunch (≈ 2 additional minutes/day; p = 0.031). Indicators of the consumption of red meat and sweet pastries significantly decreased (both adjusted p = 0.049). Neither quality of life in general nor subgroup analysis of participants with at least one conspicuous genetic risk differed significantly over follow-up. Hybrid genetic testing and counseling exerted positive effects on health-related behavior and was not associated with major psychological adverse effects in the short-term follow-up. The approach seems to be feasible for use in preventive health care.

[Diuretics as a problem-Pharmacokinetics, pharmacodynamics, use in edema or hypertension]. / Diuretika als Problem ­ Pharmakokinetik und -dynamik, Einsatz bei Ödemen oder Hypertonie.

BACKGROUND AND OBJECTIVE: Diuretics are key elements of the pharmacotherapy of diseases in internal medicine. Currently, they are particularly used in the treatment of edema and hypertension. For the treatment with diuretics some rules exist that help to improve the effectiveness and success. The article explains these rules, especially regarding combination treatment and meaningful dose escalation. Additionally, the side effects of treatment are critically discussed. RESULTS AND CONCLUSION: There is little evidence for the influence of diuretics in the treatment of edema on prognostic factors, such as mortality and comorbidities. For an improvement of the prognosis other substances are more important, e.g. angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers; however, diuretics in the treatment of hypertension show clear positive effects on the endpoints. In recent years a problem of side effects was demonstrated (skin cancer). Comparing the benefits regarding prognosis in the treatment of hypertension with the side effects, the administration but with appropriate protective measures seems to be warranted.

Telephone health coaching with exercise monitoring using wearable activity trackers (TeGeCoach) for improving walking impairment in peripheral artery disease: study protocol for a randomised controlled trial and economic evaluation.

INTRODUCTION: Peripheral artery disease (PAD) is the third most prevalent cardiovascular disease worldwide, with smoking and diabetes being the strongest risk factors. The most prominent symptom is leg pain while walking, known as intermittent claudication. To improve mobility, first-line treatment for intermittent claudication is supervised exercise programmes, but these remain largely unavailable and economically impractical, which has led to the development of structured home-based exercise programmes. This trial aims to determine the effectiveness and cost advantage of TeGeCoach, a 12-month long home-based exercise programme, compared with usual care of PAD. It is hypothesised that TeGeCoach improves walking impairment and lowers the need of health care resources that are spent on patients with PAD. METHODS AND ANALYSIS: The investigators conduct a prospective, pragmatic randomised controlled clinical trial in a health insurance setting. 1760 patients diagnosed with PAD at Fontaine stage II are randomly assigned to either TeGeCoach or care-as-usual. TeGeCoach consists of telemonitored intermittent walking exercise with medical supervision by a physician and telephone health coaching. Participants allocated to the usual care group receive information leaflets and can access supervised exercise programmes, physical therapy and a variety of programmes for promoting a healthy lifestyle. The primary outcome is patient reported walking ability based on the Walking Impairment Questionnaire. Secondary outcome measures include quality of life, health literacy and health behaviour. Claims data are used to collect total health care costs, healthcare resource use and (severe) adverse events. Outcomes are measured at baseline, 12 and 24 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Association Hamburg. Findings are disseminated through peer-reviewed journals, reports to the funding body, conference presentations and media press releases. Data from this trial are made available to the public and researchers upon reasonable request.NCT03496948 (www.clinicaltrials.gov), Pre-results.

Experience with telepathology in combination with diagnostic assistance systems in countries with restricted resources.

INTRODUCTION: We describe the use of telepathology in countries with restricted resources using two diagnosis assistance systems (Isabel and Memem7) in addition to the diagnoses made by experts in pathology via the iPath-Network. METHODS: A total of 156 cases, largely from Afghanistan, were analysed; 18 cases had to be excluded because of poor image quality. RESULTS: Of the remaining 138 cases (100%), a responsible physician provided a tentative diagnosis for 61.6% of them. With a diagnosis from a consultant pathologist, it was then possible to make a definite diagnosis in 84.8% of cases on the basis of images taken from hematoxylin and eosin staining sections alone. The use of the diagnosis assistance systems resulted in an ordered list of differential diagnoses in 82.6% (IsabelHealth) and in 74.6% (Memem7) of cases, respectively. Adding morphological terminology reduced the list of possible diagnoses to 52.2% (72 cases, Memem7), but improved their quality. DISCUSSION: In summary, diagnosis assistance systems are promising approaches to provide physicians in countries with restricted resources with lists of probable differential diagnoses, thus increasing the plausibility of the diagnosis of the consultant pathologist.