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Journal of Environmental Management May 2024This study has carried out a systematic review of 36 scientific papers (reporting 63 case studies) published in the last 15 years about the treatment of industrial,... (Meta-Analysis)
Meta-Analysis
This study has carried out a systematic review of 36 scientific papers (reporting 63 case studies) published in the last 15 years about the treatment of industrial, agri-food and municipal wastewater in lagoons. A concentration of studies from a few countries (Italy, Algeria and Iran) and about municipal wastewater (70% of papers) was revealed by the bibliographic analysis. Aeration was supplied in more than 50% of case studies; the storage capacity of lagoons (adopted as a measure of size) was extremely variable (over seven orders of magnitude), while their depth was generally lower than a few metres. The efficiency of lagoon treatments at removing COD was in a wide range (25-98%). Very few studies analysed the energy intensity of treatments in lagoons. The meta-analysis applied to a further selection of 10 papers with 29 case studies revealed significant differences in pH and dissolved oxygen concentration, due to aeration or type of treated wastewater. Treatment efficiency was higher in aerated lagoons compared to non-aerated systems, and did not depend on the type of treated wastewater. Based on the analysis of the reviewed papers, an urgent research need on this topic arises, mainly due to the oldness of most analysed studies. Practical suggestions are given to optimise the depuration performances of lagoons: (i) application of intermittent and night aeration; (ii) reduced air flow rates; (iii) adaptation of microbial biomass to high contents of inhibiting compounds in wastewater; (iv) construction of baffles to keep the planned hydraulic retention time avoiding short-circuit; (v) integration of lagoons with other treatments (e.g., constructed wetlands); (vi) ferti-irrigation of crops with lagoon effluents rather than disposal into water bodies.
Topics: Waste Disposal, Fluid; Wastewater; Water Purification
PubMed: 38701584
DOI: 10.1016/j.jenvman.2024.120974 -
Sensors (Basel, Switzerland) Mar 2024The global aging population faces significant health challenges, including an increasing vulnerability to disability due to natural aging processes. Wearable lower limb... (Review)
Review
The global aging population faces significant health challenges, including an increasing vulnerability to disability due to natural aging processes. Wearable lower limb exoskeletons (LLEs) have emerged as a promising solution to enhance physical function in older individuals. This systematic review synthesizes the use of LLEs in alignment with the WHO's healthy aging vision, examining their impact on intrinsic capacities and functional abilities. We conducted a comprehensive literature search in six databases, yielding 36 relevant articles covering older adults (65+) with various health conditions, including sarcopenia, stroke, Parkinson's Disease, osteoarthritis, and more. The interventions, spanning one to forty sessions, utilized a range of LLE technologies such as Ekso, HAL, Stride Management Assist, Honda Walking Assist, Lokomat, Walkbot, Healbot, Keeogo Rehab, EX1, overground wearable exoskeletons, Eksoband, powered ankle-foot orthoses, HAL lumbar type, Human Body Posturizer, Gait Enhancing and Motivation System, soft robotic suits, and active pelvis orthoses. The findings revealed substantial positive outcomes across diverse health conditions. LLE training led to improvements in key performance indicators, such as the 10 Meter Walk Test, Five Times Sit-to-Stand test, Timed Up and Go test, and more. Additionally, enhancements were observed in gait quality, joint mobility, muscle strength, and balance. These improvements were accompanied by reductions in sedentary behavior, pain perception, muscle exertion, and metabolic cost while walking. While longer intervention durations can aid in the rehabilitation of intrinsic capacities, even the instantaneous augmentation of functional abilities can be observed in a single session. In summary, this review demonstrates consistent and significant enhancements in critical parameters across a broad spectrum of health conditions following LLE interventions in older adults. These findings underscore the potential of LLE in promoting healthy aging and enhancing the well-being of older adults.
Topics: Humans; Aged; Exoskeleton Device; Healthy Aging; Postural Balance; Time and Motion Studies; World Health Organization
PubMed: 38610440
DOI: 10.3390/s24072230 -
Gait & Posture May 2024Backward walking is an indispensable component of activities of daily living. The backward walk test has been used to assess balance, mobility, and fall risk in... (Review)
Review
BACKGROUND
Backward walking is an indispensable component of activities of daily living. The backward walk test has been used to assess balance, mobility, and fall risk in different populations. This systematic review aimed to identify and synthesize measurement properties of the backward walk test in people with balance and mobility deficits.
METHODS
Three bibliographic databases, PubMed, Embase, and Scopus, were searched on June 18th, 2023. Cross-sectional or cohort studies assessing the measurement properties (reliability, validity, responsiveness) of the backward walk test were included. The COSMIN risk of bias checklist was used for methodological quality assessment. Study selection, data extraction, and quality assessment were completed by two reviewers independently and in duplicate.
RESULTS
A total of 786 records were identified from three databases. Fourteen studies published from 2019 to 2023 with a total of 853 participants were included. Two studies were rated inadequate in quality assessment, all other studies demonstrated adequate to very good quality. The participants population included patients with cerebral palsy, stroke, multiple sclerosis, Parkinson's disease, fibromyalgia, hip and knee arthroplasty, dementia, and community-dwelling older adults. Good interrater and intrarater reliability, and moderate to good concurrent validity of the backward walk test were demonstrated.
SIGNIFICANCE
The review demonstrates that the backward walk test appears to be a valid and reliable tool in different patient populations. The 3-meter backward walk time and 3-meter backward walk speed can be used as outcome measures in clinical practice to assess balance and mobility and track progress throughout the course of physical rehabilitation. Future studies with a prospective cohort design are required to provide information regarding the predictive validity of the backward walk test for fall risk assessment.
Topics: Humans; Postural Balance; Walk Test; Reproducibility of Results; Mobility Limitation; Accidental Falls
PubMed: 38458049
DOI: 10.1016/j.gaitpost.2024.02.018 -
NeuroRehabilitation 2024Electrical stimulation techniques are widely utilized for rehabilitation management in individuals with stroke patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Electrical stimulation techniques are widely utilized for rehabilitation management in individuals with stroke patients.
OBJECTIVES
This review aims to summarize the rehabilitative effects of electrical stimulation therapy on gait performance in stroke patients.
METHODS
This review included randomized controlled trials (RCT) investigating the therapeutic effects of electrical stimulation in stroke patients throughout five databases. This review qualitatively synthesized 20 studies and quantitatively analyzed 11 RCTs.
RESULTS
Functional electrical stimulation (FES) was the most commonly used electrical stimulation type to improve postural stability and gait performance in stroke patients. The clinical measurement tools commonly used in the three studies to assess the therapeutic effects of FES were Berg balance scale (BBS), 10-meter walk test (10MWT), 6-minute walk test (6mWT), and gait velocity. The BBS score and gait velocity had positive effects in the FES group compared with the control group, but the 10MWT and 6mWT showed the same effects between the two groups. The heterogeneity of BBS scores was also high.
CONCLUSION
The results of this review suggest that electrical stimulation shows little evidence of postural stability and gait performance in stroke patients, although some electrical stimulations showed positive effects on postural stability and gait performance.
Topics: Humans; Stroke Rehabilitation; Gait Disorders, Neurologic; Stroke; Gait; Physical Therapy Modalities; Electric Stimulation Therapy; Postural Balance
PubMed: 38306066
DOI: 10.3233/NRE-230360 -
Obesity Reviews : An Official Journal... Mar 2024Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles... (Meta-Analysis)
Meta-Analysis Review
Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles relative to the endogenous circadian timing system. This systematic review and meta-analysis aim to determine the association between social jetlag and adiposity-related measures using observational studies. We reviewed 477 references, of which 43 studies met inclusion criteria with a total sample size of 231,648. There was a positive association between social jetlag and body mass index (correlation coefficient [r]: 0.12; 95%CI, 0.07, 0.17; P < 0.001; I = 94.99%), fat mass (r: 0.10; 95%CI, 0.05, 0.15; P < 0.001; I = 0.00%), fat mass index (fat mass divided by height in meter squared, β: 0.14 kg/m ; 95%CI, 0.05, 0.23; P < 0.001; I = 56.50%), percent of body fat (r: 0.37; 95%CI, 0.33, 0.41; P < 0.001; I = 96.17%), waist circumference (r: 0.15; 95%CI, 0.06, 0.24; P = 0.001; I = 90.83%), and the risk of having overweight/obesity (odds ratio: 1.20; 95%CI, 1.02, 1.140; P = 0.039; I = 98.25%). Social jetlag is positively and consistently associated with multiple obesity-related anthropometric measures. Further studies are needed to test causality, underlying mechanisms, and whether obesity interventions based on increasing regularity of the sleep/wake cycle can aid in the battle against the obesity pandemic.
Topics: Humans; Circadian Rhythm; Obesity; Sleep; Jet Lag Syndrome; Body Mass Index; Observational Studies as Topic
PubMed: 38072635
DOI: 10.1111/obr.13664 -
Clinical Child and Family Psychology... Mar 2024Health-related Quality of Life (HRQoL) is a multi-faceted construct influenced by a myriad of environmental, demographic, and individual characteristics. Our... (Review)
Review
Health-related Quality of Life (HRQoL) is a multi-faceted construct influenced by a myriad of environmental, demographic, and individual characteristics. Our understanding of these influencers remains highly limited in neurodevelopmental conditions. Existing research in this area is sparse, highly siloed by diagnosis labels, and focused on symptoms. This review synthesized the evidence in this area using a multi-dimensional model of HRQoL and trans-diagnostically across neurodevelopmental conditions. The systematic review, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist, was completed in June 2023 using Medline, PsycInfo, Embase, PubMed, and Cochrane Library. Our search revealed 78 studies that examined predictors of HRQoL in neurodevelopmental conditions. The majority of these studies focused on autism and ADHD with a paucity of literature in other conditions. Cross-diagnosis investigations were limited despite the fact that many of the examined predictors transcend diagnostic boundaries. Significant gaps were revealed in domains of biology/physiology, functioning, health perceptions, and environmental factors. Very preliminary evidence suggested potentially shared predictors of HRQoL across conditions including positive associations between HRQoL and adaptive functioning, male sex/gender, positive self-perception, physical activity, resources, and positive family context, and negative associations with diagnostic features and mental health symptoms. Studies of transdiagnostic predictors across neurodevelopmental conditions are critically needed to enable care models that address shared needs of neurodivergent individuals beyond diagnostic boundaries. Further understanding of HRQoL from the perspective of neurodivergent communities is a critical area of future work.
Topics: Child; Humans; Male; Quality of Life
PubMed: 38070100
DOI: 10.1007/s10567-023-00462-3 -
Scandinavian Journal of Medicine &... Dec 2023Hamstring strain injury (HSI) remains a performance, economic, and player availability burden in sport. High-speed running (HSR) is cited as a common mechanism for HSI.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hamstring strain injury (HSI) remains a performance, economic, and player availability burden in sport. High-speed running (HSR) is cited as a common mechanism for HSI. While evidence exists regarding the high physical demands on the hamstring muscles in HSR, meta-analytical synthesis of related activation and kinetic variables is lacking.
METHODS
A systematic search of Medline, Embase, Scopus, CINAHL, SportDiscus, and Cochrane library databases was conducted in accordance with the PRISMA 2020 guidelines. Studies reporting hamstring activation (electromyographic [EMG]) or hamstring muscle/related joint kinetics were included where healthy adult participants ran at or beyond 60% of maximum speed (activation studies) or 4 m per second (m/s) (kinetic studies).
RESULTS
A total of 96 studies met the inclusion criteria. Run intensities were categorized as "slow," "moderate," or "fast" in both activation and kinetic based studies with appropriate relative, and raw measures, respectively. Meta-analysis revealed pooled mean lateral hamstring muscle activation levels of 108.1% (95% CI: 84.4%-131.7%) of maximal voluntary isometric contraction (MVIC) during "fast" running. Meta-analysis found swing phase peak knee flexion internal moment and power at 2.2 Newton meters/kilogram (Nm/kg) (95% CI: 1.9-2.5) and 40.3 Watts/kilogram (W/kg) (95% CI: 31.4-49.2), respectively. Hip extension peak moment and power was estimated as 4.8 Nm/kg (95% CI: 3.9-5.7) and 33.1 W/kg (95% CI: 17.4-48.9), respectively.
CONCLUSIONS
As run intensity/speed increases, so do the activation and kinetic demands on the hamstrings. The presented data will enable clinicians to incorporate more objective measures into the design of injury prevention and return-to-play decision-making strategies.
Topics: Adult; Humans; Hamstring Muscles; Kinetics; Isometric Contraction; Muscle Strength; Running; Soft Tissue Injuries
PubMed: 37668346
DOI: 10.1111/sms.14478 -
Current Urology Reports Aug 2023Urinary pH is an important factor related to renal stone disease, and it plays an essential role in stone prevention. Monitoring of urinary pH by patients at home... (Review)
Review
PURPOSE OF REVIEW
Urinary pH is an important factor related to renal stone disease, and it plays an essential role in stone prevention. Monitoring of urinary pH by patients at home provides information that can help to assess the treatment needed by each patient. We conducted a systematic review is to assess the available evidence concerning urinary pH monitoring methods along with their accuracy, cost, and usefulness by patients with urolithiasis.
RECENT FINDINGS
A total of 9 articles were included (1886 urinary pH measurements). They reported information about urinary dipsticks, portable electronic pH meters and electronic strip readers, amongst other methods. Accuracy was compared with a laboratory pH meter (gold standard). Urinary dipsticks were found to be not accurate enough to guide clinical decision making and portable electronic pH meters showed promising results. Urinary dipsticks are neither precise nor accurate enough. Portable electronic pH meters seem to be more accurate, easy to use, and cost-effective. They are a reliable source for patients to use at home in order to prevent future episodes of nephrolithiasis.
Topics: Humans; Hydrogen-Ion Concentration; Kidney Calculi; Urolithiasis; Urinary Tract; Forecasting
PubMed: 37314611
DOI: 10.1007/s11934-023-01166-5 -
The Cochrane Database of Systematic... Jun 2023Chronic venous insufficiency (CVI) is a condition related to chronic venous disease that may progress to venous leg ulceration and impair quality of life of those... (Review)
Review
BACKGROUND
Chronic venous insufficiency (CVI) is a condition related to chronic venous disease that may progress to venous leg ulceration and impair quality of life of those affected. Treatments such as physical exercise may be useful to reduce CVI symptoms. This is an update of an earlier Cochrane Review.
OBJECTIVES
To evaluate the benefits and harms of physical exercise programmes for the treatment of individuals with non-ulcerated CVI.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing exercise programmes with no exercise in people with non-ulcerated CVI.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were intensity of disease signs and symptoms, ejection fraction, venous refilling time, and incidence of venous leg ulcer. Our secondary outcomes were quality of life, exercise capacity, muscle strength, incidence of surgical intervention, and ankle joint mobility. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included five RCTs involving 146 participants. The studies compared a physical exercise group with a control group that did not perform a structured exercise programme. The exercise protocols differed between studies. We assessed three studies to be at an overall unclear risk of bias, one study at overall high risk of bias, and one study at overall low risk of bias. We were not able to combine data in meta-analysis as studies did not report all outcomes, and different methods were used to measure and report outcomes. Two studies reported intensity of CVI disease signs and symptoms using a validated scale. There was no clear difference in signs and symptoms between groups in baseline to six months after treatment (Venous Clinical Severity Score mean difference (MD) -0.38, 95% confidence interval (CI) -3.02 to 2.26; 28 participants, 1 study; very low-certainty evidence), and we are uncertain if exercise alters the intensity of signs and symptoms eight weeks after treatment (MD -4.07, 95% CI -6.53 to -1.61; 21 participants, 1 study; very low-certainty evidence). There was no clear difference in ejection fraction between groups from baseline to six months follow-up (MD 4.88, 95% CI -1.82 to 11.58; 28 participants, 1 study; very low-certainty evidence). Three studies reported on venous refilling time. We are uncertain if there is an improvement in venous refilling time between groups for baseline to six-month changes (MD 10.70 seconds, 95% CI 8.86 to 12.54; 23 participants, 1 study; very low-certainty evidence) or baseline to eight-week change (MD 9.15 seconds, 95% CI 5.53 to 12.77 for right side; MD 7.25 seconds, 95% CI 5.23 to 9.27 for left side; 21 participants, 1 study; very low-certainty evidence). There was no clear difference in venous refilling index for baseline to six-month changes (MD 0.57 mL/min, 95% CI -0.96 to 2.10; 28 participants, 1 study; very low-certainty evidence). No included studies reported the incidence of venous leg ulcers. One study reported health-related quality of life using validated instruments (Venous Insufficiency Epidemiological and Economic Study (VEINES) and 36-item Short Form Health Survey (SF-36), physical component score (PCS) and mental component score (MCS)). We are uncertain if exercise alters baseline to six-month changes in health-related quality of life between groups (VEINES-QOL: MD 4.60, 95% CI 0.78 to 8.42; SF-36 PCS: MD 5.40, 95% CI 0.63 to 10.17; SF-36 MCS: MD 0.40, 95% CI -3.85 to 4.65; 40 participants, 1 study; all very low-certainty evidence). Another study used the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20), and we are uncertain if exercise alters baseline to eight-week changes in health-related quality of life between groups (MD 39.36, 95% CI 30.18 to 48.54; 21 participants, 1 study; very low-certainty evidence). One study reported no differences between groups without presenting data. There was no clear difference between groups in exercise capacity measured as time on treadmill (baseline to six-month changes) (MD -0.53 minutes, 95% CI -5.25 to 4.19; 35 participants, 1 study; very low-certainty evidence). We are uncertain if exercise improves exercise capacity as assessed by the 6-minute walking test (MD 77.74 metres, 95% CI 58.93 to 96.55; 21 participants, 1 study; very low-certainty evidence). Muscle strength was measured using dynamometry or using heel lifts counts. We are uncertain if exercise increases peak torque/body weight (120 revolutions per minute) (changes from baseline to six months MD 3.10 ft-lb, 95% CI 0.98 to 5.22; 29 participants, 1 study; very low-certainty evidence). There was no clear difference between groups in baseline to eight-week change in strength measured by a hand dynamometer (MD 12.24 lb, 95% CI -7.61 to 32.09 for the right side; MD 11.25, 95% CI -14.10 to 36.60 for the left side; 21 participants, 1 study; very low-certainty evidence). We are uncertain if there is an increase in heel lifts (n) (baseline to six-month changes) between groups (MD 7.70, 95% CI 0.94 to 14.46; 39 participants, 1 study; very low-certainty evidence). There was no clear difference between groups in ankle mobility measured during dynamometry (baseline to six-month change MD -1.40 degrees, 95% CI -4.77 to 1.97; 29 participants, 1 study; very low-certainty evidence). We are uncertain if exercise increases plantar flexion measured by a goniometer (baseline to eight-week change MD 12.13 degrees, 95% CI 8.28 to 15.98 for right leg; MD 10.95 degrees, 95% CI 7.93 to 13.97 for left leg; 21 participants, 1 study; very low-certainty evidence). In all cases, we downgraded the certainty of evidence due to risk of bias and imprecision.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to assess the benefits and harms of physical exercise in people with chronic venous disease. Future research into the effect of physical exercise should consider types of exercise protocols (intensity, frequency, and time), sample size, blinding, and homogeneity according to the severity of disease.
Topics: Humans; Body Weight; Evidence Gaps; Exercise; Veins; Venous Insufficiency
PubMed: 37314059
DOI: 10.1002/14651858.CD010637.pub3 -
The Cochrane Database of Systematic... Mar 2023Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in... (Review)
Review
BACKGROUND
Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation.
OBJECTIVES
To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in people with PH comparing supervised exercise-based rehabilitation programmes with usual care or no exercise-based rehabilitation.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. exercise capacity, 2. serious adverse events during the intervention period and 3. health-related quality of life (HRQoL). Our secondary outcomes were 4. cardiopulmonary haemodynamics, 5. Functional Class, 6. clinical worsening during follow-up, 7. mortality and 8. changes in B-type natriuretic peptide. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included eight new studies in the current review, which now includes 14 RCTs. We extracted data from 11 studies. The studies had low- to moderate-certainty evidence with evidence downgraded due to inconsistencies in the data and performance bias. The total number of participants in meta-analyses comparing exercise-based rehabilitation to control groups was 462. The mean age of the participants in the 14 RCTs ranged from 35 to 68 years. Most participants were women and classified as Group I pulmonary arterial hypertension (PAH). Study durations ranged from 3 to 25 weeks. Exercise-based programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise-based rehabilitation was 48.52 metres higher than control (95% confidence interval (CI) 33.42 to 63.62; I² = 72%; 11 studies, 418 participants; low-certainty evidence), the mean peak oxygen uptake was 2.07 mL/kg/min higher than control (95% CI 1.57 to 2.57; I² = 67%; 7 studies, 314 participants; low-certainty evidence) and the mean peak power was 9.69 W higher than control (95% CI 5.52 to 13.85; I² = 71%; 5 studies, 226 participants; low-certainty evidence). Three studies reported five serious adverse events; however, exercise-based rehabilitation was not associated with an increased risk of serious adverse event (risk difference 0, 95% CI -0.03 to 0.03; I² = 0%; 11 studies, 439 participants; moderate-certainty evidence). The mean change in HRQoL for the 36-item Short Form (SF-36) Physical Component Score was 3.98 points higher (95% CI 1.89 to 6.07; I² = 38%; 5 studies, 187 participants; moderate-certainty evidence) and for the SF-36 Mental Component Score was 3.60 points higher (95% CI 1.21 to 5.98 points; I² = 0%; 5 RCTs, 186 participants; moderate-certainty evidence). There were similar effects in the subgroup analyses for participants with Group 1 PH versus studies of groups with mixed PH. Two studies reported mean reduction in mean pulmonary arterial pressure following exercise-based rehabilitation (mean reduction: 9.29 mmHg, 95% CI -12.96 to -5.61; I² = 0%; 2 studies, 133 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.
Topics: Female; Humans; Adult; Middle Aged; Aged; Male; Hypertension, Pulmonary; Exercise Therapy; Quality of Life; Exercise; Bias
PubMed: 36947725
DOI: 10.1002/14651858.CD011285.pub3