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Integrated disease management interventions for patients with chronic obstructive pulmonary disease.The Cochrane Database of Systematic... Sep 2021People with chronic obstructive pulmonary disease (COPD) show considerable variation in symptoms, limitations, and well-being; this often complicates medical care. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with chronic obstructive pulmonary disease (COPD) show considerable variation in symptoms, limitations, and well-being; this often complicates medical care. A multi-disciplinary and multi-component programme that addresses different elements of care could improve quality of life (QoL) and exercise tolerance, while reducing the number of exacerbations.
OBJECTIVES
To compare the effectiveness of integrated disease management (IDM) programmes versus usual care for people with chronic obstructive pulmonary disease (COPD) in terms of health-related quality of life (QoL), exercise tolerance, and exacerbation-related outcomes.
SEARCH METHODS
We searched the Cochrane Airways Group Register of Trials, CENTRAL, MEDLINE, Embase, and CINAHL for potentially eligible studies. Searches were current as of September 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared IDM programmes for COPD versus usual care were included. Interventions consisted of multi-disciplinary (two or more healthcare providers) and multi-treatment (two or more components) IDM programmes of at least three months' duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. If required, we contacted study authors to request additional data. We performed meta-analyses using random-effects modelling. We carried out sensitivity analyses for the quality of included studies and performed subgroup analyses based on setting, study design, dominant intervention components, and region.
MAIN RESULTS
Along with 26 studies included in the 2013 Cochrane Review, we added 26 studies for this update, resulting in 52 studies involving 21,086 participants for inclusion in the meta-analysis. Follow-up periods ranged between 3 and 48 months and were classified as short-term (up to 6 months), medium-term (6 to 15 months), and long-term (longer than 15 months) follow-up. Studies were conducted in 19 different countries. The mean age of included participants was 67 years, and 66% were male. Participants were treated in all types of healthcare settings, including primary (n =15), secondary (n = 22), and tertiary care (n = 5), and combined primary and secondary care (n = 10). Overall, the level of certainty of evidence was moderate to high. We found that IDM probably improves health-related QoL as measured by St. George's Respiratory Questionnaire (SGRQ) total score at medium-term follow-up (mean difference (MD) -3.89, 95% confidence interval (CI) -6.16 to -1.63; 18 RCTs, 4321 participants; moderate-certainty evidence). A comparable effect was observed at short-term follow-up (MD -3.78, 95% CI -6.29 to -1.28; 16 RCTs, 1788 participants). However, the common effect did not exceed the minimum clinically important difference (MCID) of 4 points. There was no significant difference between IDM and control for long-term follow-up and for generic QoL. IDM probably also leads to a large improvement in maximum and functional exercise capacity, as measured by six-minute walking distance (6MWD), at medium-term follow-up (MD 44.69, 95% CI 24.01 to 65.37; 13 studies, 2071 participants; moderate-certainty evidence). The effect exceeded the MCID of 35 metres and was even greater at short-term (MD 52.26, 95% CI 32.39 to 72.74; 17 RCTs, 1390 participants) and long-term (MD 48.83, 95% CI 16.37 to 80.49; 6 RCTs, 7288 participants) follow-up. The number of participants with respiratory-related admissions was reduced from 324 per 1000 participants in the control group to 235 per 1000 participants in the IDM group (odds ratio (OR) 0.64, 95% CI 0.50 to 0.81; 15 RCTs, median follow-up 12 months, 4207 participants; high-certainty evidence). Likewise, IDM probably results in a reduction in emergency department (ED) visits (OR 0.69, 95%CI 0.50 to 0.93; 9 RCTs, median follow-up 12 months, 8791 participants; moderate-certainty evidence), a slight reduction in all-cause hospital admissions (OR 0.75, 95%CI 0.57 to 0.98; 10 RCTs, median follow-up 12 months, 9030 participants; moderate-certainty evidence), and fewer hospital days per person admitted (MD -2.27, 95% CI -3.98 to -0.56; 14 RCTs, median follow-up 12 months, 3563 participants; moderate-certainty evidence). Statistically significant improvement was noted on the Medical Research Council (MRC) Dyspnoea Scale at short- and medium-term follow-up but not at long-term follow-up. No differences between groups were reported for mortality, courses of antibiotics/prednisolone, dyspnoea, and depression and anxiety scores. Subgroup analysis of dominant intervention components and regions of study suggested context- and intervention-specific effects. However, some subgroup analyses were marked by considerable heterogeneity or included few studies. These results should therefore be interpreted with caution.
AUTHORS' CONCLUSIONS
This review shows that IDM probably results in improvement in disease-specific QoL, exercise capacity, hospital admissions, and hospital days per person. Future research should evaluate which combination of IDM components and which intervention duration are most effective for IDM programmes, and should consider contextual determinants of implementation and treatment effect, including process-related outcomes, long-term follow-up, and cost-effectiveness analyses.
Topics: Aged; Disease Management; Dyspnea; Exercise Tolerance; Humans; Male; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 34495549
DOI: 10.1002/14651858.CD009437.pub3 -
The Cochrane Database of Systematic... Aug 2022Asthma is a respiratory disease characterised by variable airflow limitation and the presence of respiratory symptoms including wheeze, chest tightness, cough and/or... (Review)
Review
BACKGROUND
Asthma is a respiratory disease characterised by variable airflow limitation and the presence of respiratory symptoms including wheeze, chest tightness, cough and/or dyspnoea. Exercise training is beneficial for people with asthma; however, the response to conventional models of pulmonary rehabilitation is less clear.
OBJECTIVES
To evaluate, in adults with asthma, the effectiveness of pulmonary rehabilitation compared to usual care on exercise performance, asthma control, and quality of life (co-primary outcomes), incidence of severe asthma exacerbations/hospitalisations, mental health, muscle strength, physical activity levels, inflammatory biomarkers, and adverse events.
SEARCH METHODS
We identified studies from the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, from their inception to May 2021, as well as the reference lists of all primary studies and review articles.
SELECTION CRITERIA
We included randomised controlled trials in which pulmonary rehabilitation was compared to usual care in adults with asthma. Pulmonary rehabilitation must have included a minimum of four weeks (or eight sessions) aerobic training and education or self-management. Co-interventions were permitted; however, exercise training alone was not. DATA COLLECTION AND ANALYSIS: Following the use of Cochrane's Screen4Me workflow, two review authors independently screened and selected trials for inclusion, extracted study characteristics and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. We contacted study authors to retrieve missing data. We calculated between-group effects via mean differences (MD) or standardised mean differences (SMD) using a random-effects model. We evaluated the certainty of evidence using GRADE methodology.
MAIN RESULTS
We included 10 studies involving 894 participants (range 24 to 412 participants (n = 2 studies involving n > 100, one contributing to meta-analysis), mean age range 27 to 54 years). We identified one ongoing study and three studies awaiting classification. One study was synthesised narratively, and another involved participants specifically with asthma-COPD overlap. Most programmes were outpatient-based, lasting from three to four weeks (inpatient) or eight to 12 weeks (outpatient). Education or self-management components included breathing retraining and relaxation, nutritional advice and psychological counselling. One programme was specifically tailored for people with severe asthma. Pulmonary rehabilitation compared to usual care may increase maximal oxygen uptake (VO max) after programme completion, but the evidence is very uncertain for data derived using mL/kg/min (MD between groups of 3.63 mL/kg/min, 95% confidence interval (CI) 1.48 to 5.77; 3 studies; n = 129) and uncertain for data derived from % predicted VO max (MD 14.88%, 95% CI 9.66 to 20.1%; 2 studies; n = 60). The evidence is very uncertain about the effects of pulmonary rehabilitation compared to usual care on incremental shuttle walk test distance (MD between groups 74.0 metres, 95% CI 26.4 to 121.4; 1 study; n = 30). Pulmonary rehabilitation may have little to no effect on VOmax at longer-term follow up (9 to 12 months), but the evidence is very uncertain (MD -0.69 mL/kg/min, 95% CI -4.79 to 3.42; I = 49%; 3 studies; n = 66). Pulmonary rehabilitation likely improves functional exercise capacity as measured by 6-minute walk distance, with MD between groups after programme completion of 79.8 metres (95% CI 66.5 to 93.1; 5 studies; n = 529; moderate certainty evidence). This magnitude of mean change exceeds the minimally clinically important difference (MCID) threshold for people with chronic respiratory disease. The evidence is very uncertain about the longer-term effects one year after pulmonary rehabilitation for this outcome (MD 52.29 metres, 95% CI 0.7 to 103.88; 2 studies; n = 42). Pulmonary rehabilitation may result in a small improvement in asthma control compared to usual care as measured by Asthma Control Questionnaire (ACQ), with an MD between groups of -0.46 (95% CI -0.76 to -0.17; 2 studies; n = 93; low certainty evidence); however, data derived from the Asthma Control Test were very uncertain (MD between groups 3.34, 95% CI -2.32 to 9.01; 2 studies; n = 442). The ACQ finding approximates the MCID of 0.5 points. Pulmonary rehabilitation results in little to no difference in asthma control as measured by ACQ at nine to 12 months follow-up (MD 0.09, 95% CI -0.35 to 0.53; 2 studies; n = 48; low certainty evidence). Pulmonary rehabilitation likely results in a large improvement in quality of life as assessed by the St George's Respiratory Questionnaire (SGRQ) total score (MD -18.51, 95% CI -20.77 to -16.25; 2 studies; n = 440; moderate certainty evidence), with this magnitude of change exceeding the MCID. However, pulmonary rehabilitation may have little to no effect on Asthma Quality of Life Questionnaire (AQLQ) total scores, with the evidence being very uncertain (MD 0.87, 95% CI -0.13 to 1.86; 2 studies; n = 442). Longer-term follow-up data suggested improvements in quality of life may occur as measured by SGRQ (MD -13.4, 95% CI -15.93 to -10.88; 2 studies; n = 430) but not AQLQ (MD 0.58, 95% CI -0.23 to 1.38; 2 studies; n = 435); however, the evidence is very uncertain. One study reported no difference between groups in the proportion of participants who experienced an asthma exacerbation during the intervention period. Data from one study suggest adverse events attributable to the intervention are rare. Overall risk of bias was most commonly impacted by performance bias attributed to a lack of participant blinding to knowledge of the intervention. This is inherently challenging to overcome in rehabilitation studies. AUTHORS' CONCLUSIONS: Moderate certainty evidence shows that pulmonary rehabilitation is probably associated with clinically meaningful improvements in functional exercise capacity and quality of life upon programme completion in adults with asthma. The certainty of evidence relating to maximal exercise capacity was very low to low. Pulmonary rehabilitation appears to confer minimal effect on asthma control, although the certainty of evidence is very low to low. Unclear reporting of study methods and small sample sizes limits our certainty in the overall body of evidence, whilst heterogenous study designs and interventions likely contribute to inconsistent findings across clinical outcomes and studies. There remains considerable scope for future research.
Topics: Adult; Asthma; Dyspnea; Hospitalization; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 35993916
DOI: 10.1002/14651858.CD013485.pub2 -
The Cochrane Database of Systematic... May 2022Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After... (Review)
Review
BACKGROUND
Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes.
OBJECTIVES
To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VOpeak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible.
MAIN RESULTS
We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. Prehabilitation may also result in fewer complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250) and fewer emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250). The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. On the other hand, prehabilitation may also result in a higher re-admission rate (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250). The certainty of evidence was again low due to downgrading for risk of bias and imprecision. The effect on VOpeak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies.
AUTHORS' CONCLUSIONS
Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. Complication rates and the number of emergency department visits postoperatively may also diminish due to a prehabilitation programme, while the number of re-admissions may be higher in the prehabilitation group. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.
Topics: Colorectal Neoplasms; Humans; Length of Stay; Postoperative Complications; Preoperative Exercise; Quality of Life
PubMed: 35588252
DOI: 10.1002/14651858.CD013259.pub2 -
The Cochrane Database of Systematic... May 2023Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After... (Review)
Review
BACKGROUND
Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes.
OBJECTIVES
To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VOpeak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible.
MAIN RESULTS
We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. The effects of prehabilitation on the number of complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250), emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250) and re-admissions (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250) were small or even trivial. The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. The effects on VOpeak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies.
AUTHORS' CONCLUSIONS
Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. A solid effect on the number of omplications, postoperative emergency department visits and re-admissions could not be established. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.
Topics: Adult; Humans; Colorectal Neoplasms; Digestive System Surgical Procedures; Postoperative Complications; Preoperative Exercise; Quality of Life
PubMed: 37162250
DOI: 10.1002/14651858.CD013259.pub3 -
The Cochrane Database of Systematic... Dec 2021Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance.
OBJECTIVES
The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies.
SELECTION CRITERIA
Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE.
MAIN RESULTS
We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study.
AUTHORS' CONCLUSIONS
When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.
Topics: Ankle Brachial Index; Carnitine; Humans; Intermittent Claudication; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Walking
PubMed: 34954832
DOI: 10.1002/14651858.CD010117.pub2 -
PloS One 2022To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease.
METHODS
Randomized controlled clinical trials were identified from PubMed, Scopus, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wanfang and Chongqing VIP databases, from the database inception to 31/12/2021. The outcome measures were walking distance measured by treadmill (maximum and pain-free walking distance), ankle-brachial index and adverse events. The quality of included studies was assessed by the Cochrane bias risk assessment tool. A network meta-analysis was carried out with Stata 16.0 software.
RESULTS
There were 29 RCTs included in the study, covering total 5352 patients. Cilostazol was ranked first for both maximum and pain-free walking distance, followed by beraprost and pentoxifylline. For cilostazol, pentoxifylline and beraprost, maximum walking distance increased by 62.93 95%CI(44.06, 81.79), 32.72 95%CI(13.51, 55.79) and 43.90 95%CI(2.10, 85.71) meters, respectively relative to placebo, and pain-free walking distance increased by 23.92 95%CI(11.24, 36.61), 15.16 95%CI(2.33, 27.99) and 19.78 95%CI(-3.07, 42.62) meters. For cilostazol, pentoxifylline, beraprost and cilostazol combined with beraprost, ankle-brachial index increased by 0.06 95%CI(0.04, 0.07), -0.01 95%CI(-0.08, 0.05), 0.18 95%CI(0.12, 0.23) and 0.23 95%CI(0.18, 0.27), respectively relative to placebo. The pentoxifylline and cilostazol was associated with a lower ratio of adverse events than beraprost and cilostazol combined with beraprost.
CONCLUSION
Cilostazol, pentoxifylline and beraprost were all effective treatments for intermittent claudication; cilostazol with good tolerance was likely to be the most effective in walking distance, while beraprost and cilostazol combined with beraprost were more prominent in the ankle-brachial index.
Topics: Humans; Cilostazol; Intermittent Claudication; Network Meta-Analysis; Pentoxifylline; Vasodilator Agents; Randomized Controlled Trials as Topic
PubMed: 36318524
DOI: 10.1371/journal.pone.0275392 -
The Cochrane Database of Systematic... Jun 2021Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication (exercise-induced lower limb pain relieved by rest). These patients have a three- to six-fold increase in cardiovascular mortality. Cilostazol is a drug licensed for the use of improving claudication distance and, if shown to reduce cardiovascular risk, could offer additional clinical benefits. This is an update of the review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol on initial and absolute claudication distances, mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 9 November 2020.
SELECTION CRITERIA
We considered double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other drugs used to improve claudication distance in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We assessed the risk of bias with the Cochrane risk of bias tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and for continuous outcomes we used mean differences (MDs) and 95% CIs. We pooled data using a fixed-effect model, or a random-effects model when heterogeneity was identified. Primary outcomes were initial claudication distance (ICD) and quality of life (QoL). Secondary outcomes were absolute claudication distance (ACD), revascularisation, amputation, adverse events and cardiovascular events.
MAIN RESULTS
We included 16 double-blind, RCTs (3972 participants) comparing cilostazol with placebo, of which five studies also compared cilostazol with pentoxifylline. Treatment duration ranged from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Cilostazol dose ranged from 100 mg to 300 mg; pentoxifylline dose ranged from 800 mg to 1200 mg. The certainty of the evidence was downgraded by one level for all studies because publication bias was strongly suspected. Other reasons for downgrading were imprecision, inconsistency and selective reporting. Cilostazol versus placebo Participants taking cilostazol had a higher ICD compared with those taking placebo (MD 26.49 metres; 95% CI 18.93 to 34.05; 1722 participants; six studies; low-certainty evidence). We reported QoL measures descriptively due to insufficient statistical detail within the studies to combine the results; there was a possible indication in improvement of QoL in the cilostazol treatment groups (low-certainty evidence). Participants taking cilostazol had a higher ACD compared with those taking placebo (39.57 metres; 95% CI 21.80 to 57.33; 2360 participants; eight studies; very-low certainty evidence). The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Participants taking cilostazol had an increased odds of experiencing headache compared to participants taking placebo (OR 2.83; 95% CI 2.26 to 3.55; 2584 participants; eight studies; moderate-certainty evidence).Very few studies reported on other outcomes so conclusions on revascularisation, amputation, or cardiovascular events could not be made. Cilostazol versus pentoxifylline There was no difference detected between cilostazol and pentoxifylline for improving walking distance, both in terms of ICD (MD 20.0 metres, 95% CI -2.57 to 42.57; 417 participants; one study; low-certainty evidence); and ACD (MD 13.4 metres, 95% CI -43.50 to 70.36; 866 participants; two studies; very low-certainty evidence). One study reported on QoL; the study authors reported no difference in QoL between the treatment groups (very low-certainty evidence). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol participants had an increased odds of experiencing headache compared with participants taking pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17; 982 participants; two studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
Cilostazol has been shown to improve walking distance in people with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache. There is insufficient evidence about the effectiveness of cilostazol for serious events such as amputation, revascularisation, and cardiovascular events. Despite the importance of QoL to patients, meta-analysis could not be undertaken because of differences in measures used and reporting. Very limited data indicated no difference between cilostazol and pentoxifylline for improving walking distance and data were too limited for any conclusions on other outcomes.
Topics: Aged; Bias; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Placebos; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 34192807
DOI: 10.1002/14651858.CD003748.pub5 -
Alternative Therapies in Health and... Nov 2023Leukemia is the most prevalent cancer among children and adolescents. This study investigated the potential association between exposure to magnetic fields and the risk... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Leukemia is the most prevalent cancer among children and adolescents. This study investigated the potential association between exposure to magnetic fields and the risk of pediatric leukemia.
METHODS
We conducted a comprehensive search of electronic databases, including Scopus, EMBASE, Cochrane, Web of Science, and Medline, up to December 15, 2022, to identify relevant studies examining the link between childhood leukemia and magnetic field exposure.
RESULTS
The first meta-analysis revealed a statistically significant inverse association between pediatric leukemia and magnetic field strengths ranging from 0.4 μT to 0.2 μT, suggesting a reduced risk associated with this range. The second meta-analysis focused on wiring configuration codes and observed a potential link between residential magnetic field exposure and childhood leukemia. Pooled relative risk estimates were 1.52 (95% CI = 1.05-2.04, P = .021) and 1.58 (95% CI = 1.15-2.23, P = .006) for exposure to 24-hour magnetic field measurements, suggesting a possible causal relationship. In the third meta-analysis, the odds ratios for the exposure groups of 0.1 to 0.2 μT, 0.2 to 0.3 μT, 0.3 to 0.4 μT, and 0.4 μT above 0.2 μT were 1.09 (95% confidence interval = 0.82 to 1.43 μT), 1.14 (95% confidence interval = 0.68 to 1.92 μT), and 1.45 (95% confidence interval = 0.87 to 2.37 μT), respectively. In contrast to the findings of the three meta-analyses, there was no evidence of a statistically significant connection between exposure to 0.2 μT and the risk of juvenile leukemia. A further result showed no discernible difference between the two groups of children who lived less than 100 meters from the source of magnetic fields and those who lived closer (OR = 1.33; 95% CI = 0.98-1.73 μT).
CONCLUSIONS
The collective results of three meta-analyses, encompassing magnetic field strengths ranging from 0.1 μT to 2.38 μT, underscore a statistically significant association between the intensity of magnetic fields and the occurrence of childhood leukemia. However, one specific analysis concluded that no apparent relationship exists between exposure to 0.1 μT and an elevated risk of leukemia development in children.
Topics: Adolescent; Child; Humans; Electromagnetic Fields; Leukemia; Magnetic Fields; Neoplasms; Electromagnetic Radiation; Environmental Exposure; Case-Control Studies
PubMed: 37678874
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2022Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of... (Review)
Review
BACKGROUND
Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of respiratory problems. Bronchodilator therapy is used to relieve symptoms of shortness of breath and to open the airways to allow clearance of mucus. Despite the widespread use of inhaled bronchodilators in CF, there is little objective evidence of their efficacy. A Cochrane Review looking at both short- and long-acting inhaled bronchodilators for CF was withdrawn from the Cochrane Library in 2016. That review has been replaced by two separate Cochrane Reviews: one on long-acting inhaled bronchodilators for CF, and this review on short-acting inhaled bronchodilators for CF. For this review 'inhaled' includes the use of pressurised metered dose inhalers (MDIs), with or without a spacer, dry powder devices and nebulisers.
OBJECTIVES
To evaluate short-acting inhaled bronchodilators in children and adults with CF in terms of clinical outcomes and safety.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books on 28 March 2022 and searched trial registries for any new or ongoing trials on 12 April 2022. We also searched the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) or quasi-RCTs that looked at the effect of any short-acting inhaled bronchodilator delivered by any device, at any dose, at any frequency and for any duration compared to either placebo or another short-acting inhaled bronchodilator in people with CF. We screened references as per standard Cochrane methodology.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and assessed risk of bias using the Cochrane RoB 1 tool. Where we were not able to enter data into our analyses we reported results directly from the papers. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 11 trials from our systematic search, with 191 participants meeting our inclusion criteria; three of these trials had three treatment arms. Eight trials compared short-acting inhaled beta-2 agonists to placebo and four trials compared short-acting inhaled muscarinic antagonists to placebo. Three trials compared short-acting inhaled beta-2 agonists to short-acting inhaled muscarinic antagonists. All were cross-over trials with only small numbers of participants. We were only able to enter data into the analysis from three trials comparing short-acting inhaled beta-2 agonists to placebo. Short-acting inhaled beta-2 agonists versus placebo All eight trials (six single-dose trials and two longer-term trials) reporting on this comparison reported on forced expiratory volume in 1 second (FEV), either as per cent predicted (% predicted) or L. We were able to combine the data from two trials in a meta-analysis which showed a greater per cent change from baseline in FEV L after beta-2 agonists compared to placebo (mean difference (MD) 6.95%, 95% confidence interval (CI) 1.88 to 12.02; 2 trials, 82 participants). Only one of the longer-term trials reported on exacerbations, as measured by hospitalisations and courses of antibiotics. Only the second longer-term trial presented results for participant-reported outcomes. Three trials narratively reported adverse events, and these were all mild. Three single-dose trials and the two longer trials reported on forced vital capacity (FVC), and five trials reported on peak expiratory flow, i.e. forced expiratory flow between 25% and 75% (FEF). One trial reported on airway clearance in terms of sputum weight. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists on any of the outcomes we assessed. Short-acting inhaled muscarinic antagonists versus placebo All four trials reporting on this comparison looked at the effects of ipratropium bromide, but in different doses and via different delivery methods. One trial reported FEV % predicted; three trials measured this in L. Two trials reported adverse events, but these were few and mild. One trial reported FVC and three trials reported FEF. None of the trials reported on quality of life, exacerbations or airway clearance. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled muscarinic antagonists on any of the outcomes we assessed. Short-acting inhaled beta-2 agonists versus short-acting inhaled muscarinic antagonists None of the three single-dose trials reporting on this comparison provided data we could analyse. The original papers from three trials report that both treatments lead to an improvement in FEV L. Only one trial reported on adverse events; but none were experienced by any participant. No trial reported on any of our other outcomes. We judged the certainty of evidence to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists compared to short-acting inhaled muscarinic antagonists on any of the outcomes we assessed.
AUTHORS' CONCLUSIONS
All included trials in this review are small and of a cross-over design. Most trials looked at very short-term effects of inhaled bronchodilators, and therefore did not measure longer-term outcomes. The certainty of evidence across all outcomes was very low, and therefore we have been unable to describe any effects with certainty.
Topics: Administration, Inhalation; Adult; Bronchodilator Agents; Child; Cystic Fibrosis; Forced Expiratory Volume; Humans; Muscarinic Antagonists
PubMed: 35749226
DOI: 10.1002/14651858.CD013666.pub2 -
The Cochrane Database of Systematic... Apr 2021Bronchiectasis is characterised by excessive sputum production, chronic cough, and acute exacerbations and is associated with symptoms of dyspnoea and fatigue, which... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bronchiectasis is characterised by excessive sputum production, chronic cough, and acute exacerbations and is associated with symptoms of dyspnoea and fatigue, which reduce exercise tolerance and impair quality of life. Exercise training in isolation or in conjunction with other interventions is beneficial for people with other respiratory diseases, but its effects in bronchiectasis have not been well established.
OBJECTIVES
To determine effects of exercise training compared to usual care on exercise tolerance (primary outcome), quality of life (primary outcome), incidence of acute exacerbation and hospitalisation, respiratory and mental health symptoms, physical function, mortality, and adverse events in people with stable or acute exacerbation of bronchiectasis.
SEARCH METHODS
We identified trials from the Cochrane Airways Specialised Register, ClinicalTrials.gov, and the World Health Organization trials portal, from their inception to October 2020. We reviewed respiratory conference abstracts and reference lists of all primary studies and review articles for additional references.
SELECTION CRITERIA
We included randomised controlled trials in which exercise training of at least four weeks' duration (or eight sessions) was compared to usual care for people with stable bronchiectasis or experiencing an acute exacerbation. Co-interventions with exercise training including education, respiratory muscle training, and airway clearance therapy were permitted if also applied as part of usual care.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected trials for inclusion, extracted outcome data, and assessed risk of bias. We contacted study authors for missing data. We calculated mean differences (MDs) using a random-effects model. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included six studies, two of which were published as abstracts, with a total of 275 participants. Five studies were undertaken with people with clinically stable bronchiectasis, and one pilot study was undertaken post acute exacerbation. All studies included co-interventions such as instructions for airway clearance therapy and/or breathing strategies, provision of an educational booklet, and delivery of educational sessions. The duration of training ranged from six to eight weeks, with a mix of supervised and unsupervised sessions conducted in the outpatient or home setting. No studies of children were included in the review; however we identified two studies as currently ongoing. No data were available regarding physical activity levels or adverse events. For people with stable bronchiectasis, evidence suggests that exercise training compared to usual care improves functional exercise tolerance as measured by the incremental shuttle walk distance, with a mean difference (MD) between groups of 87 metres (95% confidence interval (CI) 43 to 132 metres; 4 studies, 161 participants; low-certainty evidence). Evidence also suggests that exercise training improves six-minute walk distance (6MWD) (MD between groups of 42 metres, 95% CI 22 to 62; 1 study, 76 participants; low-certainty evidence). The magnitude of these observed mean changes appears clinically relevant as they exceed minimal clinically important difference (MCID) thresholds for people with chronic lung disease. Evidence suggests that quality of life improves following exercise training according to St George's Respiratory Questionnaire (SGRQ) total score (MD -9.62 points, 95% CI -15.67 to -3.56 points; 3 studies, 160 participants; low-certainty evidence), which exceeds the MCID of 4 points for this outcome. A reduction in dyspnoea (MD 1.0 points, 95% CI 0.47 to 1.53; 1 study, 76 participants) and fatigue (MD 1.51 points, 95% CI 0.80 to 2.22 points; 1 study, 76 participants) was observed following exercise training according to these domains of the Chronic Respiratory Disease Questionnaire. However, there was no change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ) (MD -0.09 points, 95% CI -0.98 to 0.80 points; 2 studies, 103 participants; moderate-certainty evidence), nor in anxiety or depression. Two studies reported longer-term outcomes up to 12 months after intervention completion; however exercise training did not appear to improve exercise capacity or quality of life more than usual care. Exercise training reduced the number of acute exacerbations of bronchiectasis over 12 months in people with stable bronchiectasis (odds ratio 0.26, 95% CI 0.08 to 0.81; 1 study, 55 participants). After an acute exacerbation of bronchiectasis, data from a single study (N = 27) suggest that exercise training compared to usual care confers little to no effect on exercise capacity (MD 11 metres, 95% CI -27 to 49 metres; low-certainty evidence), SGRQ total score (MD 6.34 points, 95%CI -17.08 to 29.76 points), or LCQ score (MD -0.08 points, 95% CI -0.94 to 0.78 points; low-certainty evidence) and does not reduce the time to first exacerbation (hazard ratio 0.83, 95% CI 0.31 to 2.22).
AUTHORS' CONCLUSIONS
This review provides low-certainty evidence suggesting improvement in functional exercise capacity and quality of life immediately following exercise training in people with stable bronchiectasis; however the effects of exercise training on cough-related quality of life and psychological symptoms appear to be minimal. Due to inadequate reporting of methods, small study numbers, and variation between study findings, evidence is of very low to moderate certainty. Limited evidence is available to show longer-term effects of exercise training on these outcomes.
Topics: Adult; Bias; Breathing Exercises; Bronchiectasis; Cough; Disease Progression; Dyspnea; Exercise; Exercise Tolerance; Hospitalization; Humans; Mental Health; Physical Endurance; Physical Functional Performance; Quality of Life; Respiration Disorders; Walk Test
PubMed: 33822364
DOI: 10.1002/14651858.CD013110.pub2