Impairment of Inspiratory Muscle Function after COVID-19.

BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.

How to Implement Adherence-Promoting Programs in Clinical Practice? A Discrete Choice Experiment on Physicians' Preferences.

INTRODUCTION: The aim of this study was to examine physicians' preferences regarding adherence-promoting programs (APPs), and to investigate which APP characteristics influence the willingness of physicians to implement these in daily practice. MATERIALS AND METHODS: A discrete choice experiment was conducted among general practitioners, cardiologists, neurologists and ophthalmologists in Germany. The design considered five attributes with two or three attribute levels each: validation status of the APP; possibility for physicians to receive a certificate; type of intervention; time commitment per patient and quarter of the year to carry out the APP; reimbursement for APP participation, per included patient and quarter of the year.A multinomial logit model was run to estimate physicians' utility for each attribute and to evaluate the influence of different levels on the probability of choosing a specific APP. The relative importance of the attributes was compared between different pre-defined subgroups. RESULTS: In total, 222 physicians were included in the analysis. The most important characteristics of APPs were time commitment to carry out the program (34.8% importance), reimbursement (33.3%), and validation status of the program (23.7%). The remaining attributes (type of intervention: 3.6%; possibility to receive a certificate: 4.7%) were proven to be less important for a physician's decision to participate in an APP. Physicians on average preferred APP alternatives characterized by little time commitment (ß=1.456, p<0.001), high reimbursement for work (ß=1.392, p<0.001), "positive validation status" (ß=0.990, p<0.001), the "possibility to get a certificate" (ß=0.197, p<0.001), and the provision of "tools for both physicians and patients" (ß=0.150, p<0.001). CONCLUSION: For the majority of the physicians participating in this survey, the willingness to implement an APP is determined by the associated time commitment and reimbursement. Considering physicians' preferences regarding different APP features in the promoting process of these programs may enhance physicians' participation and engagement.

Incidental findings during computed tomographic angiography diagnostic work-up in patients with arteriogenic erectile dysfunction.

AIM: To analyse the incidental findings during computed tomographic angiography (CTA) diagnostic work-up in patients with arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS: The medical records of all patients with suspected arteriogenic ED were entered into a database. Risk factors and underlying comorbidities were also collected. Pathological CTA findings were extracted from the CT readings and entered into the database. Incidental findings on CTA were classified as those requiring immediate medical treatment, requiring deferred medical treatment or of no clinical importance. RESULTS: A total of 200 patients underwent CTA for suspected arteriogenic ED. Mean patient age was 59.6 ± 11.7 years. Of these, 181 patients (90.5%) had obstructions of erection-related arteries. In 168 patients (84.0%), CTA showed multiple incidental pathological findings. Eighty-five of 200 patients (42.5%) exhibited incidental findings requiring immediate further medical workup and/or treatment: coronary artery calcification was diagnosed in 75/200 (37.5%), aorto-iliac aneurysms in 8/200 (4%) of patients and incidentally detected embolism in 1/200 patient. Pancreatic and liver tumours were less frequent (incidence 1.5% and 1%, respectively). Incidental findings requiring deferred medical workup and/or treatment were detected in 175/200 patients (87.5%). The findings with the highest prevalence were liver steatosis followed by colon diverticulosis and prostate hyperplasia. Findings of little to no clinical importance were reported in 117 (58.5%) patients. These included uncomplicated renal cysts, spinal degeneration and renal vascular anomalies. Almost every second patient presenting with ED had an incidental finding which required immediate treatment. CONCLUSIONS: Incidental findings not directly related to ED were common among patients undergoing CTA scans for suspected arterial obstructions. Coronary artery calcification was the leading finding requiring further medical workup and/or treatment. Thus, the benefit of CTA investigations extends beyond the anatomic description of arterial obstructions of erection-related arteries.

Gamma-glutamyl transferase as a risk factor for mortality and cardiovascular events in older adults - results from a prospective cohort study in a primary care setting (getABI).

Background: In primary care, the gamma-glutamyl transferase (GGT) activity is used for assessing hepatobiliary dysfunction, but is also known to be associated with the risk of cardiovascular events as well as overall mortality. As this knowledge is mainly based on cohorts with middle-aged participants, we aim to assess these associations in elderly patients in a primary care setting. Patients and methods: 6,880 unselected primary care patients, aged 65 years or older, were enrolled by 344 general practitioners all over Germany (getABI study). During seven years of follow-up, coronary heart disease (CHD) events (myocardial infarction or coronary revascularization), cerebrovascular events (stroke or carotid revascularization) and deaths were recorded. Event rates were calculated and Cox regression analysis with adjustment for age, gender, GGT, classical and other risk factors (e.g. education, homocysteine, C-reactive protein, vitamin D) was performed. Results: 1,243 patients died. 27.8 deaths per 1,000 patient years (0.95 confidence interval [0.95 CI]: 26.2-29.3) occurred in the whole cohort. 605 participants had a CHD event, i.e. 16.1 per 1,000 patient years (0.95 CI: 14.8-17.4). 296 cerebrovascular events were observed, i.e. 7.7 per 1,000 patient years (0.95 CI: 6.9-8.6). Cox regression analysis with adjustment for the above-mentioned risk factors showed a significant impact of baseline elevation of GGT above the 3rd quartile (women > 18 U/L, men > 26 U/L) compared to the rest on mortality (hazard ratio [HR] 1.38, 95% CI 1.22-1.56, p < 0.001) and cerebrovascular events (1.39, 95% CI: 1.08-1.79), p = 0.010), whereas the association with CHD events (HR: 1.16, 95% CI: 0.97-1.39, p = 0.103) showed no significance. Conclusions: In a primary care setting, GGT values have a significant association with overall mortality and cerebrovascular events, but not with CHD events in elderly patients.

Interactions between C-reactive protein and traditional risk factors in predicting mortality of older adults.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. PATIENTS AND METHODS: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. RESULTS: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. CONCLUSIONS: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.

Access, timing and frequency of very early stroke rehabilitation - insights from the Baden-Wuerttemberg stroke registry.

BACKGROUND: While the precise timing and intensity of very early rehabilitation (VER) after stroke onset is still under discussion, its beneficial effect on functional disability is generally accepted. The recently published randomized controlled AVERT trial indicated that patients with severe stroke might be more susceptible to harmful side effects of VER, which we hypothesized is contrary to current clinical practice. We analyzed the Baden-Wuerttemberg stroke registry to gain insight into the application of VER in acute ischemic stroke (IS) and intracerebral hemorrhage (ICH) in clinical practice. METHODS: 99,753 IS patients and 8824 patients with ICH hospitalized from January 2008 to December 2012 were analyzed. Data on the access to physical therapy (PT), occupational therapy (OT), and speech therapy (ST), the time from admission to first contact with a therapist and the average number of therapy sessions during the first 7 days of admission are reported. Multiple logistic regression models adjusted for patient and treatment characteristics were carried out to investigate the influence of VER on clinical outcome. RESULTS: PT was applied in 90/87% (IS/ICH), OT in 63/57%, and ST in 70/65% of the study population. Therapy was mostly initiated within 24 h (PT 87/82%) or 48 h after admission (OT 91/89% and ST 93/90%). Percentages of patients under therapy and also the average number of therapy sessions were highest in those with a discharge modified Rankin Scale score of 2 to 5 and lowest in patients with complete recovery or death during hospitalization. The outcome analyses were fundamentally hindered due to biases by individual decision making regarding the application and frequency of VER. CONCLUSIONS: While most patients had access to PT we noticed an undersupply of OT and ST. Only little differences were observed between patients with IS and ICH. The staff decisions for treatment seem to reflect attempts to optimize resources. Patients with either excellent or very unfavorable prognosis were less frequently assigned to VER and, if treated, received a lower average number of therapy sessions. On the contrary, severely disabled patients received VER at high frequency, although potentially harmful according to recent indications from the randomized controlled AVERT trial.

The risk of peripheral artery disease in older adults - seven-year results of the getABI study.

BACKGROUND: To assess the risk of peripheral artery disease (PAD) in older adults and the contribution of traditional and novel risk factors to the incidence of PAD. PATIENTS AND METHODS: 344 general practitioners (GPs), trained by vascular specialists all over Germany, enrolled 6,880 unselected participants aged 65 years or older (getABI study). The onset of PAD was determined by a regression method in the course of repeated measurements of the ankle brachial index (ABI) over seven years. PAD onset was defined by the declining linear regression ABI line reaching 0.9 or by PAD symptoms. RESULTS: The cumulative PAD incidence over seven years was 12.9%, corresponding to an incidence rate of 20.3 per 1000 person years (95% confidence interval [95%CI] 18.8 to 21.7). Logistic regression analysis showed that traditional risk factors contributed significantly to the risk of PAD: current smoker status (odds ratio 2.65, 95%CI 2.08 to 3.37), diabetes (1.35, 95%CI 1.13 to 1.62), and low-density lipoprotein >130 mg/dl (1.26, 95%CI 1.07 to 1.48). Three novel risk factor candidates showed significant impact on PAD incidence: elevated sensitive C-reactive protein level (1.23, 95%CI 1.05 to 1.45), impaired estimated glomerular filtration rate (1.27, 95%CI 1.03 to 1.56), and elevated homocysteine level (1.19, 95%CI 1.01 to 1.41). CONCLUSIONS: Older adults in Germany have a PAD risk of 12.9% per seven years. Potentially modifiable traditional PAD risk factors yield high impact on PAD incidence. Novel risk factor candidates may contribute to the risk of PAD.

Restriction of therapy mainly explains lower thrombolysis rates in reduced stroke service levels.

OBJECTIVE: To assess the influence of preexisting disabilities, age, and stroke service level on standardized IV thrombolysis (IVT) rates in acute ischemic stroke (AIS). METHODS: We investigated standardized IVT rates in a retrospective registry-based study in 36,901 patients with AIS from the federal German state Baden-Wuerttemberg over a 5-year period. Patients admitted within 4.5 hours after stroke onset were selected. Factors associated with IVT rates (patient-level factors and stroke service level) were assessed using robust Poisson regression modeling. Interactions between factors were considered to estimate risk-adjusted mortality rates and potential IVT rates by service level (with stroke centers as benchmark). RESULTS: Overall, 10,499 patients (28.5%) received IVT. The IVT rate declined with service level from 44.0% (stroke center) to 13.1% (hospitals without stroke unit [SU]). Especially patients >80 years of age and with preexisting disabilities had a lower chance of being treated with IVT at lower stroke service levels. Interactions between stroke service level and age group, preexisting disabilities, and stroke severity (all p < 0.0001) were observed. High IVT rates seemed not to increase mortality. Estimated potential IVT rates ranged between 41.9% and 44.6% depending on stroke service level. CONCLUSIONS: Differences in IVT rates among stroke service levels were mainly explained by differences administering IVT to older patients and patients with preexisting disabilities. This indicates considerable further potential to increase IVT rates. Our findings support guideline recommendations to admit acute stroke patients to SUs.

[Update PAVK: Epidemiology, comorbidity and prognosis of peripheral arterial obstructive disease]. / Periphere arterielle Verschlusskrankheit: Epidemiologie, Komorbidität und Prognose.

The number of patients suffering from PAD is increasing worlwide and the rate of hospitalized patients in Germany is continously increasing. The diagnosis can be made reliably by ankle- and toe-pressure measurements with calculating the ABI and TBI. Clinical relevant comorbidities are CAD, heart insuffiency , chronic renal failure and diabetes. The prognosis of asymptomatic and symptomatic patients is characterized by an increased cardiovascular morbidity and mortality.

Intravenous Thrombolysis is Effective in Young Adults: Results from the Baden-Wuerttemberg Stroke Registry.

BACKGROUND: The efficacy of intravenous thrombolysis (IVT) is sufficiently proven in ischemic stroke patients of middle and older age by means of randomized controlled trials and large observational studies. However, data in young stroke patients ≤50 years are still scarce. In this study, we aimed to evaluate the effectiveness and safety of IVT in young adults aged 18-50 years. Data from a consecutive and prospective stroke registry was analyzed that covers a federal state with 10.8 million inhabitants in southwest Germany. METHODS: Our analysis comprises 51,735 ischemic stroke patients aged 18-80 years and hospitalized from January 2008 to December 2012. Of these, 4,140 (8%) were aged 18-50 years and 7,529 (15%) underwent IVT. Data on 8,439 patients (16% of the study population) were missing for National Institutes of Health stroke severity score at admission and/or modified Rankin Scale (mRS) at discharge and were excluded from outcome analysis. In sensitivity analysis, patients with incomplete data were also examined. Binary logistic regression models were used adjusted for patient, hospital, and procedural parameters and stratified by age group (18-50 and 51-80 years, subgroup analyses 18-30, 31-40, and 41-50 years) to assess the relationship between IVT and mRS at discharge. RESULTS: IVT appears equally effective in young adults 18-50 years (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.75; p = 0.003), compared to patients 51-80 years of age (1.33, 1.23-1.43; p < 0.001). Age-stratified analyses suggest an inverse relation of age and effectiveness, which appears to be highest in very young patients 18-30 years of age (2.78, 1.10-7.05; p = 0.03). DISCUSSION: Ischemic stroke etiology, vascular dynamics, and recovery in young patients differ from those of middle and older age. The evidence from routine hospital care in Germany indicates that IVT in young stroke patients appears to be at least equally effective as in the elderly.

Prevalence of deep vein thrombosis in acutely admitted ambulatory non-surgical intensive care unit patients.

BACKGROUND: Data on prevalence rates of venous thromboembolism (VTE) in different patient populations are scarce. Most studies on this topic focus on older patients or patients with malignancies, immobilization or thrombophilia. Less is known about the VTE risk profile of non-surgical patients presenting with a variety of medical diseases of differing severity. Aim of the present study was to investigate VTE prevalence in a pospective cohort study of ambulatory medical intensive care unit patients within 24 h after acute admission. METHODS: Prospective cohort study of 102 consecutive patients after acute admission to medical intensive care unit. Ultrasound compression sonography, APACHE-II-Scoring and laboratory examination was performed within 24 hours after admission.Possible determinants of a high risk of VTE were examined. In all patients with a confirmed diagnosis of DVT or suspicion of PE thoracic computer tomography (CT) was performed. RESULTS: VTE was found in 7.8% out of 102 of patients, mean APACHE-II-Score was 14 (mortality risk of about 15%). Thrombus location was femoropopliteal in 5 patients, iliacal in 2 and peroneal in 1 patient. Five VTE patients had concomitant PE (62.5% of VTE, 4.9% of all patients). No predictors of prevalent VTE were identified from univariable regression analysis although relative risk was high in patients with a history of smoking (RR 3.40), immobility (RR 2.50), and elevated D-Dimer levels (RR 3.49). CONCLUSIONS: Prevalent VTE and concomitant PE were frequent in acutely admitted ICU patients.

Non-coronary atherosclerosis.

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

Alprostadil infusion in patients with dry age related macular degeneration: a randomized controlled clinical trial.

BACKGROUND: Age-related macular degeneration is the leading cause of blindness among elderly individuals in industrialized countries. New drugs and advanced concepts for the treatment of dry AMD (dAMD) are needed. A new approach is the application of intravenous infusions of prostaglandin E1. OBJECTIVE: The aim of this study was to assess efficacy and safety of intravenous alprostadil infusion in patients with dAMD. METHODS: This was a prospective, randomized, multi-center study. Patients were treated with intravenous infusion of either 60 µg alprostadil or placebo over 3 weeks. Main efficacy outcomes were mean differences in best corrected visual acuity (BCVA) from baseline assessed in early treatment diabetic retinopathy study (ETDRS) lines immediately, 3 months and 6 months after treatment. RESULTS: In the full analysis set (FAS) a mean difference of 0.89 ± 0.537 ETDRS lines according to analysis of variance-covariance (ANCOVA) resulted in the alprostadil group (n = 16) and a mean difference of -0.05 ± 0.578 in the placebo group (n = 17) 3 months after end of treatment. Thus, effectiveness of alprostadil infusion was numerically superior to placebo treatment by a mean of 0.94 lines after 3 months (1.51 lines after 6 months). These findings were more pronounced in the per protocol set (PPS). Safety results were in line with the good safety profile of alprostadil. CONCLUSION: A numerical treatment effect in favor of alprostadil was visible, which lasted until the end of follow up. These results provide further evidence that alprostadil probably has a therapeutic effect in the treatment of dAMD and justify further clinical studies.

Physical activity promotion in primary health care: results from a German physician survey.

BACKGROUND: Primary care physicians are positioned to play an important role in changing physical activity and other health behaviour of their patients. However, little is known about the practice of physical activity promotion in German primary care settings and the factors associated with physical activity promotion. METHODS: 260 randomly selected physicians from the State Medical Association of Baden-Wuerttemberg, Germany, took part in this survey (response rate: 13.3%) and provided data on physical activity promotion (physical activity assessment and advice), attitudes towards health promotion and cooperation activities. Factors associated with physical activity promotion were identified using logistic regression. RESULTS: The physicians who replied had positive attitudes towards health promotion. However, 26.9% reported they had inadequate knowledge to provide counselling and 36.7% felt they were unsuccessful in motivating their patients to increase physical activity. Physical activity assessment and advice occurred in 54.9% of the physicians. Compared to their counterparts, physicians in large cities (odds ratio (OR) 3.93; and 95% confidence interval (95%CI): 1.55-9.99), those convinced to offer their patients a great deal in the way of lifestyle counselling (OR 1.92; 95%CI: 1.09-3.40) and those cooperating with sports clubs (OR 1.75; 95%CI: 1.03-2.96) were more likely to provide physical activity promotion. CONCLUSION: There is a need for interventions to increase the frequency of physical activity promotion by primary care physicians. In particular physicians in rural regions should be assisted and cooperation activities with sports clubs or other health care providers should be encouraged.

Behavioral counseling for cardiovascular disease prevention in primary care settings: a systematic review of practice and associated factors.

Cardiovascular disease carries a substantial public health burden. Physician advice on modifying behavioral risk factors is effective, yet the practice of and factors associated with behavioral counseling in primary care have not been systematically investigated. The authors conducted a systematic review that identified 18 studies providing data on 6,338 physicians. The provision of preventive services differed by patients' individual risk. Physicians' counseling on smoking cessation was most commonly reported. The proportions of physicians counseling about nutrition and physical activity were notably lower and few physicians took further action by using more intensive counseling approaches. As studies were mainly based on self-reports, current delivery of preventive services may be overestimated. There is a need to increase the frequency of behavioral counseling in primary care settings, particularly for nutrition and physical activity, and to emphasize that counseling may also benefit individuals without cardiovascular disease risk factors.

Effect of nebivolol vs. hydrochlorothiazide on the walking capacity in hypertensive patients with intermittent claudication.

AIMS: Whereas product labels of beta blockers list peripheral arterial disease (PAD) as a contraindication, current PAD guidelines state otherwise. We aimed to evaluate the clinical efficacy and safety of the ß(1) selective blocker nebivolol in hypertensive patients with PAD. METHODS AND RESULTS: This multicentre, prospective, double-blind, active controlled, parallel-group study compared once-daily treatment with nebivolol (Neb) 5 mg vs. hydrochlorothiazide (HCTZ) 25 mg, in hypertensive patients with Fontaine stage II (intermittent claudication). The primary endpoint was the initial claudication distance (ICD) during treadmill exercise after 24-week treatment in the per protocol population, using a noninferiority statistical approach. A total of 177 patients (mean age was 66.3 ± 9.2 years, 76.7% men) were randomized to study treatment and 127 completed the study; the intent-to-treat (ITT) analysis was performed on 163 patients, the per protocol analysis on 127 patients. Both drugs lowered blood pressure significantly. After 24-week treatment, ICD increased in the Neb group in the ITT population by 28.3% (95% CI 15.6-41.0) vs. in the HCTZ group by 26.5% (14.4-38.5), and in the per protocol population in the Neb group by 26.4% (13.4-39.4) vs. in the HCTZ group by 32.1% (18.4-45.7). Thus, noninferiority of Neb could neither be confirmed nor rejected. An increase of absolute claudication distance (ACD, mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6) was observed without statistical differences between groups. Ankle-brachial index (ABI) increased slightly in both groups. Generally, both treatments were well tolerated. CONCLUSION: The increases in ICD, ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD, and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability.