Influence of Diabetes Mellitus on Glaucoma-Relevant Examination Results in Primary Open-Angle Glaucoma. / Einflussnahme des Diabetes mellitus auf glaukomrelevante Untersuchungsergebnisse beim primären Offenwinkelglaukom.

Primary open-angle glaucoma (POAG) is no longer considered an isolated eye pressure-dependent optic neuropathy, but a neurodegenerative disease in which oxidative stress and neuroinflammation are prominent. These processes may be exacerbated by additional systemic diseases. The most common are arterial hypertension, dyslipidemia, and diabetes mellitus. Using diabetes mellitus as an example, it will be shown how far-reaching the influence of such a systemic disease can be on both the functional and the structural diagnostic methods for POAG. This knowledge is essential, since these interferences can lead to misinterpretations of POAG, which can also affect therapeutic decisions.

Neuroprotective Effects of Anti-diabetic Drugs in the Treatment of Patients with Diabetes and Glaucoma or at High Risk for Glaucoma. / Neuroprotektive Wirkungen von Antidiabetika in der Therapie von Patienten mit Diabetes und Glaukom oder hohem Glaukomrisiko.

There is an association between glaucoma and several risk factors and metabolic diseases, such as type 2 diabetes mellitus. Diabetes mellitus leads to neurodegenerative changes, both peripherally and in the brain. This might be a shared pathophysiology and etiology for both glaucoma and diabetes. It is interesting that drugs for the treatment of diabetes seem to have neuroprotective properties independent of their blood sugar reduction. Although prospective, randomized, clinical studies are still missing, particularly metformin and glucagon-like peptide receptor agonists (GLP 1 RA) seem to have neuroprotective effects. Sulphonylureas (e.g., glibenclamide, glimepiride) are still used. They frequently potently reduce blood pressure but may be less neuroprotective. In the present review, the evidence for neuroprotective effects of the different antidiabetic drugs is presented and a possible differential therapy for patients with diabetes and glaucoma, or at high risk of glaucoma, will be discussed.

Exercise Training for Patients With Peripheral Arterial Occlusive Disease.

BACKGROUND: One-third of all persons with peripheral arterial occlusive disease (PAOD) suffer from intermittent claudication. Exercise training under appropriate supervision is recommended in the pertinent guidelines, but physicians order it too rarely, and so-called vascular exercise groups are not available everywhere. This situation needs improvement in view of the impor - tance of walking ability and cardiorespiratory fitness for patients' quality of life and long-term disease outcome. METHODS: We review the scientific evidence on exercise training and on ways to lower barriers to the ordering of exercise training and to patient participation, on the basis of pertinent articles retrieved by a search of PubMed and in specialized sports science journals. RESULTS: 10 meta-analyses, 12 randomized controlled trials (RCTs), and 7 cohort studies were considered for this review. Largescale cohort studies have shown that exercise is associated with a lower risk of death (relative risk 0.65-0.78 after 12 months of exercise training, compared to an inactive lifestyle). Exercise training also improves the maximal walking distance by a mean of 136 m (training at home) or 180-310 m (supervised training). An additional improvement by a mean of 282 m can be expected from a combination of exercise training and endovascular revascularization. Further behavior-modifying interventions, such as goal-setting, planning, and feedback, increase both the maximum walking distance and the weekly duration of exercise. CONCLUSION: Exercise improves walking ability and lowers mortality. To attract patients with intermittent claudication to exercise training, a broad assortment of analog, digital and telemetric tools and a dense network of vascular exercise groups should be made available, along with regular contact between physicians and patients.

Improved Persistence to Medication, Decreased Cardiovascular Events and Reduced All-Cause Mortality in Hypertensive Patients With Use of Single-Pill Combinations: Results From the START-Study.

BACKGROUND: Single-pill combination improves adherence and persistence to medication in hypertension. It remains unclear whether this also reduces cardiovascular outcomes and all-cause mortality. We analyzed whether single-pill combinations are superior to identical multiple pills on persistence to medication, cardiovascular outcomes, and all-cause mortality. METHODS: This was a retrospective claims data (German AOK PLUS) analysis. Data from hypertensive patients ≥18 years treated with renin-angiotensin system combinations given as single pill or identical multipills covering the years 2012 to 2018 were analyzed and followed up to at least 1 year. After 1:1 propensity score matching, persistence to medication, cardiovascular events, and all-cause mortality were compared using non-parametric tests. Results were reported as incidence rate ratios and hazard ratios. RESULTS: After propensity score matching data from 57 998 patients were analyzed: 10 801 patients received valsartan/amlodipine, 1026 candesartan/amlodipine, 15 349 ramipril/amlodipine, and 1823 amlodipine/valsartan/hydrochlorothiazide as single pill or identical multipill. No relevant differences in patient characteristics were observed within the 4 groups. In all groups, a significant lower all-cause mortality, a significant a higher persistence to medication, a significant lower event rate in 15 out of 20 comparisons, and a tendency in the remaining 5 comparisons was observed under single pills compared with multipill combinations. CONCLUSIONS: Antihypertensive combination therapy reduces all-cause mortality and cardiovascular events when provided as single pill compared to identical drugs as multipills. This strongly supports the European Society of Cardiology/European Society of Hypertension and International Society of Hypertension guidelines recommending the use of a single-pill combination and thus should be more rigorously implemented into daily clinical practice.

CORE-CERT Items as a Minimal Requirement for Replicability of Exercise Interventions: Results From Application to Exercise Studies for Breast Cancer Patients.

ABSTRACT: Hacke, C, Knuth, J, Bucher, M, Weisser, B, and Schmidt, T. CORE-CERT items as a minimal requirement for replicability of exercise interventions: results from application to exercise studies for breast cancer patients. J Strength Cond Res 37(5): e346-e360, 2023-Exercise interventions have been demonstrated to be useful in the prevention and therapy for multiple different diseases. The Consensus on Exercise Reporting Template (CERT) has been developed as the reporting guideline for exercise studies. The main goals of CERT are to ensure completeness of reporting, to enable interpretation of exercise programs, and to allow extraction of data for meta-analyses and the development of guidelines. However, for clinicians, the most important aspect of good reporting might be the replicability of protocols for their patients. This study was designed to determine the core components of exercise interventions for breast cancer, which are considered as minimal requirement for replicability in practice. The original items of CERT were specified, subdivided, or extended by additional key items to develop a "CORE-CERT checklist." The original CERT and our CORE-CERT were then applied to 29 exercise RCTs for breast cancer obtained from the most frequently cited and most recent meta-analyses in current guidelines. The reporting quality using both templates were examined. Mean original CERT score was 11 of 19 (59%) of completed items and 13 of 19 (68%) of reporting completeness for CORE-CERT. Reporting quality using CORE-CERT items was approximately 8% higher, indicating a more precise description of items in CORE-CERT. Differences concerned exercise dosage, nonexercise components, supervision, and description of each exercise. We propose a novel CORE-CERT guideline necessary for the replicability of exercise interventions in clinical practice. The application of CORE-CERT demonstrated a slightly better but still insufficient reporting quality of exercise interventions for breast cancer.

Interval Training in Sports Medicine: Current Thoughts on an Old Idea.

In light of the global physical inactivity pandemic, the increasing prevalence of non-committable diseases, and mounting healthcare costs, effective and feasible prevention and treatment approaches are urgently needed [...].

Diving ergospirometry with suspended weights: breathing- and fin-swimming style matter.

PURPOSE: Scuba diving is a complex condition including elevated ambient pressure, limited air supply, increased breathing work, and unfamiliar fin-swimming. Earlier approaches to assess diving specific data did not comprehensively address these aspects. We first present an underwater ergospirometry system and then test the hypothesis that both breathing characteristics and fin-swimming style affect the air consumption. METHODS/PARTICIPANTS: A suspended-weights ergospirometry system was mounted inside a hyperbaric chamber. Ergo group: 25 divers (24.6 ± 4.1 years); three set-ups: dry normobaric cycling (75-225 W), dry cycling at 20 m simulated depth (75-225 W), fin-swimming at 20 m (5-8 kg suspended weights). Style group: 20 other divers (24.6 ± 4.1 years): fin-swimming at 20 m (5-8 kg) with regard to ventilation ([Formula: see text]E) and fin-swimming style. RESULTS: Ergo group: linear heart rate and oxygen uptake ([Formula: see text]O2) increases with both 50 W-bicycle steps and suspended-weights ergometry (r = 0.97). During hyperbaric conditions, [Formula: see text]E was less increased versus normobaric conditions. Style group: the more efficient hip/thigh-oriented style shifted towards the knee/calf-oriented style. [Formula: see text]E and [Formula: see text]O2 were higher in beginners (< 100 dives) versus advanced divers (≥ 100 dives). Significant differences on the 5 kg-step: [Formula: see text]E: 31.5 ± 7.1 l/min vs. 23.7 ± 5.9 l/min and [Formula: see text]O2: 1.6 ± 0.3 l/min vs. 1.2 ± 0.3 l/min. A comparison is presented, in addition to illustrate the impact of differences in breathing characteristics and fin-swimming style. CONCLUSIONS: Diving ergospirometry with suspended weights in a hyperbaric chamber allows for comprehensive studies. Little diving experience in terms of breathing characteristics and fin-swimming style significantly increases [Formula: see text]E thereby increasing the risk of running-out-of-air.

Effects of Single Pill Combinations Compared to Identical Multi Pill Therapy on Outcomes in Hypertension, Dyslipidemia and Secondary Cardiovascular Prevention: The START-Study.

AIM: Current guidelines for the treatment of arterial hypertension (AH) or cardiovascular (CV) prevention recommend combination drug treatments with single pill combinations (SPC) to improve adherence to treatment. We aimed to assess whether the SPC concept is clinically superior to multi pill combination (MPC) with identical drugs. METHODS AND RESULTS: In an explorative study, we analyzed anonymized claims data sets of patients treated with CV drugs for hypertension and/or CV disorders who were insured by the German AOK PLUS statutory health fund covering 01/07/2012-30/06/2018. Patients at age ≥18 years who received either a SPC or MPC with identical drugs were followed for up to one year. A one to one propensity score matching (PSM) was applied within patient groups who started identical drug combinations, and results were reported as incidence rate ratios (IRRs) as well as hazard ratios (HRs). After PSM, data from 59,336 patients were analyzed. In 30 out of 56 IRR analyses, superiority of SPC over MPC was shown. In 5 out of 7 comparisons, the HR for the composite outcome of all-cause death and all-cause hospitalizations was in favor of the SPC regimen (SPC versus MPC): valsartan/amlodipine: HR=0.87 (95% CI: 0.84-0.91, p ≤ 0.001); candesartan/amlodipine: 0.77 (95% CI: 0.65-0.90, p = 0.001); valsartan/amlodipine/hydrochlorothiazide: HR=0.68 (95% CI: 0.61-0.74, p ≤ 0.001); ramipril/amlodipine: HR=0.80 (95% CI: 0.77-0.83, p ≤ 0.001); acetylsalicylic acid (ASA)/atorvastatin/ramipril: HR=0.64 (95% CI: 0.47-0.88, p = 0.005). CONCLUSION: SPC regimens are associated with a lower incidence of CV events and lower all-cause mortality in clinical practice. SPC regimens should generally be preferred to improve patient's prognosis.

Effects of cardiovascular single pill combinations compared with identical multi-pill therapies on healthcare cost and utilization in Germany.

Aim: This study assessed whether a single pill combination (SPC) is associated with lower direct healthcare costs. Materials & methods: Anonymized claims data of patients ≥18 years treated with drugs for cardiovascular (CV)-related diseases either as a single pill combination or multi-pill combination (follow-up to 1 year) were evaluated. After propensity score matching, 59,336 out of 1,369,840 patients were analyzed. Results: In all cohorts, patients receiving a single pill combination had a lower frequency of general practitioner and specialist visits. The patients also had a significantly lower ratio of all-cause hospitalization days and number of CV-related prescriptions as well as all-cause prescriptions (with one exception) compared with those receiving a multi-pill combination. Conclusion: Direct CV-related costs were significantly lower in four out of seven comparisons, with a trend toward lower costs in the other three comparisons.

Application of the Templates TIDieR and CERT Reveal Incomplete Reporting and Poor Replicability of Exercise Interventions for Type 2 Diabetes Mellitus.

BACKGROUND: Exercise is strongly recommended for the management of type 2 diabetes mellitus (T2DM). However, incomplete intervention reporting in clinical trials limits the replication of exercise protocols. As previously demonstrated by us for exercise and hypertension, the reporting quality might also be insufficient in studies with respect to T2DM and exercise. OBJECTIVE: The aim of the study was to assess the completeness of exercise intervention reporting in randomized controlled trials (RCTs) for T2DM. METHODS: Two independent reviewers applied the Consensus on Exercise Reporting Template (CERT) and the template for intervention description and replication (TIDieR) to 23 exercise trials obtained from the most recent and frequently cited meta-analysis in current guidelines. The completeness of reporting was evaluated, focusing on the F.I.T.T. components (frequency, intensity, time, type). Interrater agreement and associations with publication year and journal impact factor were examined. RESULTS: Mean CERT score was 11/19 (range 5-17), and 8/12 (range 4-12) for TIDieR. F.I.T.T. components were almost completely described, whereas overall completeness of exercise reporting was 60% and 68% (CERT and TIDieR). Replication of each exercise of the respective program was not possible in 52% of interventions. The majority of items had shown excellent agreement. No associations with publication year or impact factor were found. CONCLUSION: Exercise interventions were not found to be sufficiently reported in RCTs that currently guide clinical practice in T2DM. Replication in further studies or clinical practice is limited due to poor exercise description. We suggest the use of more specific CERT for reporting results of exercise interventions. Further refinement for internal diseases is needed to better describe exercise interventions.

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study.

BACKGROUND: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements. RESULTS: Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis. CONCLUSIONS: We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology. TRIAL REGISTRATION: DRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered.

How many gait initiation trials are necessary to reliably detect anticipatory postural adjustments and first step characteristics in healthy elderly and people with Parkinson's disease?

BACKGROUND: The gait initiation (GI) process can be characterized by anticipatory postural adjustments (APAs) and first step characteristics. However, even within a constrained environment, it is unclear how many trials are necessary to obtain a reliable measurement of the GI process within one assessment. RESEARCH QUESTION: How many gait initiation trials are necessary to reliably detect APAs and first step characteristics in healthy elderly (HC) and people with Parkinson's disease with Freezing of Gait (PD + FOG) under single (ST) and dual task (DT) conditions and are there any potential systematic errors? METHODS: Thirty-eight PD + FOG (ON-medication) and 30 HC performed 5 trials of GI under ST and DT (auditory stroop test). APAs and first-step-outcomes were captured with IMUs placed on the lower back and on each foot. Intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM) were computed to investigate reliability and mixed model analysis to find potential systematic errors. Additionally, we computed an estimation for the number of necessary trials to reach acceptable reliability (ICC = 0.75) for each outcome. RESULTS: ICCs varied from low reliability to excellent reliability across outcomes in PD + FOG and HC. ICCs were comparable under ST and DT for most outcomes. SEM results confirmed the ICC results. A systematic error was found for the first trial in first step ROM. Number of necessary trials varied largely across outcomes. SIGNIFICANCE: Within-session reliability varied across outcomes but was similar for PD + FOG and HC, and ST and DT. ML size of APA and first step ROM were most reliable, whereas APA duration and latency were least reliable. Depending on the outcome of interest, future studies should conduct multiple trials of GI to increase reliability.

Monitoring of Treatment for Arterial Hypertension­The Role of Office, Home, and 24 h Ambulatory Blood Pressure Measurement.

BACKGROUND: The treatment of arterial hypertension can be monitored by office blood pressure (office BP), home blood pressure (home BP), or 24 hours ambulatory blood pressure (ABPM). In this review, we present current recommendations from Germany and from international guidelines as well as the findings of the main studies on the use of these methods to guide treatment. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed up to and including March 2020. Special attention was paid to guidelines and position papers. RESULTS: The guidelines offer heterogeneous recommendations for treatment monitoring. Home BP is the most reproducible method, with test-retest correlation coefficients of 0.91/0.86 (systolic/diastolic), in comparison to office BP (0.77/0.76). Two meta-analyses revealed better blood pressure control with home measurement than with usual care (systolic, -3.2 to -8.9 mmHg). A meta-analysis of randomized controlled trials also suggests that home measurement promotes adherence. In the randomized and controlled TASMINH4 trial, the home BP group with telemetric surveillance achieved better blood pressure control than the group with treatment titration based on office BP (systolic -4.7 [CI: -7; -2.4] mmHg, diastolic -1.3 [-2.5; 0.02] mmHg). With ABPM, patients frequently reported moderate to severe discomfort, limiting its practical applicability. CONCLUSION: Blood pressure measurement at home is recommended for treatment monitoring, using validated, automatic upper arm devices with data storage and trend analysis. Changes of treatment should be based on average values (28 home measurements) from seven days (two morning and two evening measurements per day). Office BP is mainly used for for screening purposes. There have not yet been any randomized trials comparing the three measuring methods in terms of hard cardiovascular endpoints.

[Sport and exercise in prevention and therapy of cardiovascular diseases]. / Sport und Bewegung in Prävention und Therapie kardiovaskulärer Erkrankungen.

Sport and exercise improve physical performance, quality of life and prognosis in virtually all cardiovascular risk factors and diseases. Not only moderate endurance exercise but also specific strength training programs are recommended. However, research and practice are also focusing on more intense, interval exercise and targeted interventions to improve performance. In the primary and secondary prevention of cardiovascular diseases, adapted strength training without press breathing is also suitable.In addition to moderate endurance training, higher-intensity, interval-type exercise is now recommended for individual patients. An individually adapted load control is important after exhaustion in the load ECG. Rules of thumb should not be applied. With the exception of nicotine cessation, an improvement in physical performance is the most effective measure in terms of prognosis. Increased daily activity measured by a daily step count of more than 7500, optimally more than 10 000, also has a positive effect.

Validation of the German Version of the New Freezing of Gait Questionnaire for People with Parkinson's Disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is a highly disabling symptom which impacts quality of life. The New FOG Questionnaire (NFOG-Q) is the most commonly used tool worldwide to characterize FOG severity in PD. This study aims to provide a German translation of the NFOG-Q and to assess its validity in people with PD. The questionnaire was translated using forward-backward translation. Validity was tested in 57 PD patients with FOG via Cronbach's alpha for internal consistency and Spearman correlations with several clinical measures to quantify disease severity, mobility, fall risk, and cognitive state for convergent and divergent validity. The German version of the NFOG-Q shows good internal consistency (Cα = 0.84). Furthermore, the NFOG-Q score was significantly correlated with the MDS-UPDRS III, H&Y stage, Timed Up and Go test, and the subjective fear of falling (FES-I). The lack of correlation with cognition (MoCA) points towards good divergent validity. This study provides a German version of the NFOG-Q which proved to be valid for the assessment of FOG severity in individuals with PD.

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.

Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents?

INTRODUCTION AND OBJECTIVES: To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril). METHODS: This was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg and atorvastatin 40mg on SBP and LDL-C. The coprimary endpoints were differences in the adjusted mean 24-hour SBP (using ambulatory BP measurement) and LDL-C during the study period estimated using an ANCOVA model. RESULTS: Of the 241 patients included in the per protocol population, 84 received the CNIC polypill (group A), 84 atorvastatin (group B), and 73 ramipril (group C). SBP decreased from 139.3±12.5 to 133.2±12.9mmHg in group A and from 138.1±11.9 to 134.0±12.8mmHg in group C (baseline adjusted mean difference for the decrease in SBP was 1.77mmHg (90%CI, -0.5 to 4.0) in favor of group A, without reaching statistical significance. LDL-C was reduced by 33.9±21.6 and 29.2±25.8mg/dL in groups A and B, respectively (baseline adjusted mean difference for the decrease in LDL-C was 7.0% (90%CI, 1.5-12.4), a significantly greater decrease with the polypill). The 3 treatments were well tolerated. CONCLUSIONS: The results of this study rule out a negative effect on blood pressure of the interaction between the components of the CNIC polypill. The reduction in LDL-C was greater in the CNIC polypill group, suggesting a synergistic effect of the components.

The Effect of One Session Split-Belt Treadmill Training on Gait Adaptation in People With Parkinson's Disease and Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with gait asymmetry and switching difficulty. A split-belt treadmill may potentially address those deficits. OBJECTIVE: To investigate the immediate and retention effects of one-session split-belt treadmill training (SBT) in contrast to regular tied-belt treadmill training (TBT) on gait asymmetry and adaptation in people with PD and FOG (PD + FOG) and healthy controls (HC). Additionally, to investigate differential effects of 3 SBT protocols and compare different gait adaptation outcomes. METHODS: PD + FOG (n = 45) and HC (n = 36) were randomized to 1 of 3 SBT groups (belt speeds' ratio 0.75:1; 0.5:1 or changing ratios) or TBT group. Participants were tested at Pre, Post, and Retention after one treadmill training session. Gait asymmetry was measured during a standardized adaptation test on the split-belt treadmill. RESULTS: SBT proved beneficial for gait adaptation in PD + FOG and HC (P < .0001); however, HC improved more. SBT with changing ratios demonstrated significant effects on gait adaptation from Pre to Post in PD + FOG, supported by strong effect sizes (d = 1.14) and improvements being retained for 24 hours. Mean step length asymmetry during initial exposure was lower in HC compared with PD + FOG (P = .035) and differentiated best between the groups. CONCLUSIONS: PD + FOG improved gait adaptation after a single SBT session although effects were smaller than in HC. SBT with changing ratios was the most effective to ameliorate gait adaptation in PD + FOG. These promising results warrant future study on whether long-term SBT strengthens adaptation in PD + FOG and has potential to induce a better resilience to FOG. Clinical trial ID: NCT03725215.

Single Pill Regimen Leads to Better Adherence and Clinical Outcome in Daily Practice in Patients Suffering from Hypertension and/or Dyslipidemia: Results of a Meta-Analysis.

INTRODUCTION: Cardiovascular diseases (CVD) represent the first cause of mortality in western countries. Hypertension and dyslipidemia are strong risk factors for CVD, and are prevalent either alone or in combination. Although effective substances for the treatment of both factors are available, there is space for optimization of treatment regimens due to poor patient's adherence to medication, which is usually a combination of several substances. Adherence decreases with the number of pills a patient needs to take. A combination of substances in one single-pill (single pill combination, SPC), might increase adherence, and lead to a better clinical outcome. AIM: We conducted a meta-analysis to compare the effect of SPC with that of free-combination treatment (FCT) in patients with either hypertension, dyslipidemia or the combination of both diseases under conditions of daily practice. METHODS: Studies were identified by searching in PubMed from November 2014 until February 2015. Search criteria focused on trials in identical hypertension and/or dyslipidemia treatment as FCT therapy or as SPC. Adherence and persistence outcome included proportion-of-days-covered (PDC), medication possession ratio (MPR), time-to treatment gap of 30 and 60 days and no treatment gap of 30 days (y/n). Clinical outcomes were all cause hospitalisation, hypertension-related hospitalisation, all cause emergency room visits, hypertension-related emergency room visits, outpatient visits, hypertension-related outpatient visits, and number of patients reaching blood pressure goal. Randomized clinical studies were excluded because they usually do not reflect daily practice. RESULTS: 11 out of 1.465 studies met the predefined inclusion criteria. PDC ≥ 80% showed an odds ratio (OR) of 1.78 (95% CI: 1.30-2.45; p = 0.004) after 6 months and an OR of 1.85 (95% CI: 1.71; 2.37; p < 0.001) after ≥ 12 months in favour to the SPC. MPR ≥ 80% after 12 months also was in favour to SPC (OR 2.13; 95% CI: 1.30; 3.47; p = 0.003). Persistence was positively affected by SPC after 6, 12, and 18 months. Time to treatment gap of 60 days resulted in a hazard ratio (HR) of 2.03 (95% CI: 1.77; 2.33, p < 0.001). The use of SPC was associated with a significant improvement in systolic blood pressure reduction, leading to a higher number of patients reaching individual blood pressure goals (FCT vs SPC results in OR = 0.77; 95% CI: 0.69; 0.85, p < 0.001). Outpatient visits, emergency room visits and hospitalisations, both overall and hypertension-related were reduced by SPC: all-cause hospitalisation (SPC vs FCT: 15.0% vs 18.2%, OR 0.79, 95% CI 0.67; 0.94, p = 0.009), all-cause emergency room visits (SPC vs FCT: 25.7% vs 31.4%, OR 0.75, 95% CI 0.65; 0.87, p = 0.001) and hypertension related emergency room visits (SPC vs FCT: 9.7% vs 14.1%, OR 0.65, 95% CI 0.54; 0.80, p < 0.001). CONCLUSIONS: SPC improved medication adherence and clinical outcome parameter in patients suffering from hypertension and/or dyslipidemia and led to a better clinical outcome compared to FCT under conditions of daily practice.