Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery.

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, VO2peak, 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 VO2peak, 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.

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery.

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, VO2peak, 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 VO2peak, 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.

Modes of exercise training for intermittent claudication.

BACKGROUND: According to international guidelines and literature, all patients with intermittent claudication should receive an initial treatment of cardiovascular risk modification, lifestyle coaching, and supervised exercise therapy. In the literature, supervised exercise therapy often consists of treadmill or track walking. However, alternative modes of exercise therapy have been described and yielded similar results to walking. This raises the following question: which exercise mode produces the most favourable results? This is the first update of the original review published in 2014. OBJECTIVES: To assess the effects of alternative modes of supervised exercise therapy compared to traditional walking exercise in patients with intermittent claudication. 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 4 March 2019. We also undertook reference checking, citation searching and contact with study authors to identify additional studies. No language restriction was applied. SELECTION CRITERIA: We included parallel-group randomised controlled trials comparing alternative modes of exercise training or combinations of exercise modes with a control group of supervised walking exercise in patients with clinically determined intermittent claudication. The supervised walking programme needed to be supervised at least twice a week for a consecutive six weeks of training. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data, and assessed the risk of bias for each study. As we included studies with different treadmill test protocols and different measuring units (metres, minutes, or seconds), the standardised mean difference (SMD) approach was used for summary statistics of mean walking distance (MWD) and pain-free walking distance (PFWD). Summary estimates were obtained for all outcome measures using a random-effects model. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: For this update, five additional studies were included, making a total of 10 studies that randomised a total of 527 participants with intermittent claudication (IC). The alternative modes of exercise therapy included cycling, lower-extremity resistance training, upper-arm ergometry, Nordic walking, and combinations of exercise modes. Besides randomised controlled trials, two quasi-randomised trials were included. Overall risk of bias in included studies varied from high to low. According to GRADE criteria, the certainty of the evidence was downgraded to low, due to the relatively small sample sizes, clinical inconsistency, and inclusion of three studies with risk of bias concerns. Overall, comparing alternative exercise modes versus walking showed no clear differences for MWD at 12 weeks (standardised mean difference (SMD) -0.01, 95% confidence interval (CI) -0.29 to 0.27; P = 0.95; 6 studies; 274 participants; low-certainty evidence); or at the end of training (SMD -0.11, 95% CI -0.33 to 0.11; P = 0.32; 9 studies; 412 participants; low-certainty evidence). Similarly, no clear differences were detected in PFWD at 12 weeks (SMD -0.01, 95% CI -0.26 to 0.25; P = 0.97; 5 studies; 249 participants; low-certainty evidence); or at the end of training (SMD -0.06, 95% CI -0.30 to 0.17; P = 0.59; 8 studies, 382 participants; low-certainty evidence). Four studies reported on health-related quality of life (HR-QoL) and three studies reported on functional impairment. As the studies used different measurements, meta-analysis was only possible for the walking impairment questionnaire (WIQ) distance score, which demonstrated little or no difference between groups (MD -5.52, 95% CI -17.41 to 6.36; P = 0.36; 2 studies; 96 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: This review found no clear difference between alternative exercise modes and supervised walking exercise in improving the maximum and pain-free walking distance in patients with intermittent claudication. The certainty of this evidence was judged to be low, due to clinical inconsistency, small sample size and risk of bias concerns. The findings of this review indicate that alternative exercise modes may be useful when supervised walking exercise is not an option. More RCTs with adequate methodological quality and sufficient power are needed to provide solid evidence for comparisons between each alternative exercise mode and the current standard of supervised treadmill walking. Future RCTs should investigate outcome measures on walking behaviour, physical activity, cardiovascular risk, and HR-QoL, using standardised testing methods and reporting of outcomes to allow meaningful comparison across studies.

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication.

BACKGROUND: Although supervised exercise therapy (SET) provides significant symptomatic benefit for patients with intermittent claudication (IC), it remains an underutilized tool. Widespread implementation of SET is restricted by lack of facilities and funding. Structured home-based exercise therapy (HBET) with an observation component (e.g., exercise logbooks, pedometers) and just walking advice (WA) are alternatives to SET. This is the second update of a review first published in 2006. OBJECTIVES: The primary objective was to provide an accurate overview of studies evaluating effects of SET programs, HBET programs, and WA on maximal treadmill walking distance or time (MWD/T) for patients with IC. Secondary objectives were to evaluate effects of SET, HBET, and WA on pain-free treadmill walking distance or time (PFWD/T), quality of life, and self-reported functional impairment. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (December 16, 2016) and the Cochrane Central Register of Controlled Trials (2016, Issue 11). We searched the reference lists of relevant studies identified through searches for other potential trials. We applied no restriction on language of publication. SELECTION CRITERIA: We included parallel-group randomized controlled trials comparing SET programs with HBET programs and WA in participants with IC. We excluded studies in which control groups did not receive exercise or walking advice (maintained normal physical activity). We also excluded studies comparing exercise with percutaneous transluminal angioplasty, bypass surgery, or drug therapy. DATA COLLECTION AND ANALYSIS: Three review authors (DH, HF, and LG) independently selected trials, extracted data, and assessed trials for risk of bias. Two other review authors (MvdH and JT) confirmed the suitability and methodological quality of trials. For all continuous outcomes, we extracted the number of participants, mean outcome, and standard deviation for each treatment group through the follow-up period, if available. We extracted Medical Outcomes Study Short Form 36 outcomes to assess quality of life, and Walking Impairment Questionnaire outcomes to assess self-reported functional impairment. As investigators used different scales to present results of walking distance and time, we standardized reported data to effect sizes to enable calculation of an overall standardized mean difference (SMD). We obtained summary estimates for all outcome measures using a random-effects model. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: For this update, we included seven additional studies, making a total of 21 included studies, which involved a total of 1400 participants: 635 received SET, 320 received HBET, and 445 received WA. In general, SET and HBET programs consisted of three exercise sessions per week. Follow-up ranged from six weeks to two years. Most trials used a treadmill walking test to investigate effects of exercise therapy on walking capacity. However, two trials assessed only quality of life, functional impairment, and/or walking behavior (i.e., daily steps measured by pedometer). The overall methodological quality of included trials was moderate to good. However, some trials were small with respect to numbers of participants, ranging from 20 to 304.SET groups showed clear improvement in MWD/T compared with HBET and WA groups, with overall SMDs at three months of 0.37 (95% confidence interval [CI] 0.12 to 0.62; P = 0.004; moderate-quality evidence) and 0.80 (95% CI 0.53 to 1.07; P < 0.00001; high-quality evidence), respectively. This translates to differences in increased MWD of approximately 120 and 210 meters in favor of SET groups. Data show improvements for up to six and 12 months, respectively. The HBET group did not show improvement in MWD/T compared with the WA group (SMD 0.30, 95% CI -0.45 to 1.05; P = 0.43; moderate-quality evidence).Compared with HBET, SET was more beneficial for PFWD/T but had no effect on quality of life parameters nor on self-reported functional impairment. Compared with WA, SET was more beneficial for PFWD/T and self-reported functional impairment, as well as for some quality of life parameters (e.g., physical functioning, pain, and physical component summary after 12 months), and HBET had no effect.Data show no obvious effects on mortality rates. Thirteen of the 1400 participants died, but no deaths were related to exercise therapy. Overall, adherence to SET was approximately 80%, which was similar to that reported with HBET. Only limited adherence data were available for WA groups. AUTHORS' CONCLUSIONS: Evidence of moderate and high quality shows that SET provides an important benefit for treadmill-measured walking distance (MWD and PFWD) compared with HBET and WA, respectively. Although its clinical relevance has not been definitively demonstrated, this benefit translates to increased MWD of 120 and 210 meters after three months in SET groups. These increased walking distances are likely to have a positive impact on the lives of patients with IC. Data provide no clear evidence of a difference between HBET and WA. Trials show no clear differences in quality of life parameters nor in self-reported functional impairment between SET and HBET. However, evidence is of low and very low quality, respectively. Investigators detected some improvements in quality of life favoring SET over WA, but analyses were limited by small numbers of studies and participants. Future studies should focus on disease-specific quality of life and other functional outcomes, such as walking behavior and physical activity, as well as on long-term follow-up.

Endovascular revascularisation versus conservative management for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is the classic symptomatic form of peripheral arterial disease affecting an estimated 4.5% of the general population aged 40 years and older. Patients with IC experience limitations in their ambulatory function resulting in functional disability and impaired quality of life (QoL). Endovascular revascularisation has been proposed as an effective treatment for patients with IC and is increasingly performed. OBJECTIVES: The main objective of this systematic review is to summarise the (added) effects of endovascular revascularisation on functional performance and QoL in the management of IC. SEARCH METHODS: For this review the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). The CIS also searched trials registries for details of ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing endovascular revascularisation (± conservative therapy consisting of supervised exercise or pharmacotherapy) versus no therapy (except advice to exercise) or versus conservative therapy (i.e. supervised exercise or pharmacotherapy) for IC. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data, and assessed the methodological quality of studies. Given large variation in the intensity of treadmill protocols to assess walking distances and use of different instruments to assess QoL, we used standardised mean difference (SMD) as treatment effect for continuous outcome measures to allow standardisation of results and calculated the pooled SMD as treatment effect size in meta-analyses. We interpreted pooled SMDs using rules of thumb (< 0.40 = small, 0.40 to 0.70 = moderate, > 0.70 = large effect) according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated the pooled treatment effect size for dichotomous outcome measures as odds ratio (OR). MAIN RESULTS: We identified ten RCTs (1087 participants) assessing the value of endovascular revascularisation in the management of IC. These RCTs compared endovascular revascularisation versus no specific treatment for IC or conservative therapy or a combination therapy of endovascular revascularisation plus conservative therapy versus conservative therapy alone. In the included studies, conservative treatment consisted of supervised exercise or pharmacotherapy with cilostazol 100 mg twice daily. The quality of the evidence ranged from low to high and was downgraded mainly owing to substantial heterogeneity and small sample size.Comparing endovascular revascularisation versus no specific treatment for IC (except advice to exercise) showed a moderate effect on maximum walking distance (MWD) (SMD 0.70, 95% confidence interval (CI) 0.31 to 1.08; 3 studies; 125 participants; moderate-quality evidence) and a large effect on pain-free walking distance (PFWD) (SMD 1.29, 95% CI 0.90 to 1.68; 3 studies; 125 participants; moderate-quality evidence) in favour of endovascular revascularisation. Long-term follow-up in two studies (103 participants) showed no clear differences between groups for MWD (SMD 0.67, 95% CI -0.30 to 1.63; low-quality evidence) and PFWD (SMD 0.69, 95% CI -0.45 to 1.82; low-quality evidence). The number of secondary invasive interventions (OR 0.81, 95% CI 0.12 to 5.28; 2 studies; 118 participants; moderate-quality evidence) was also not different between groups. One study reported no differences in disease-specific QoL after two years.Data from five studies (n = 345) comparing endovascular revascularisation versus supervised exercise showed no clear differences between groups for MWD (SMD -0.42, 95% CI -0.87 to 0.04; moderate-quality evidence) and PFWD (SMD -0.05, 95% CI -0.38 to 0.29; moderate-quality evidence). Similarliy, long-term follow-up in three studies (184 participants) revealed no differences between groups for MWD (SMD -0.02, 95% CI -0.36 to 0.32; moderate-quality evidence) and PFWD (SMD 0.11, 95% CI -0.26 to 0.48; moderate-quality evidence). In addition, high-quality evidence showed no difference between groups in the number of secondary invasive interventions (OR 1.40, 95% CI 0.70 to 2.80; 4 studies; 395 participants) and in disease-specific QoL (SMD 0.18, 95% CI -0.04 to 0.41; 3 studies; 301 participants).Comparing endovascular revascularisation plus supervised exercise versus supervised exercise alone showed no clear differences between groups for MWD (SMD 0.26, 95% CI -0.13 to 0.64; 3 studies; 432 participants; moderate-quality evidence) and PFWD (SMD 0.33, 95% CI -0.26 to 0.93; 2 studies; 305 participants; moderate-quality evidence). Long-term follow-up in one study (106 participants) revealed a large effect on MWD (SMD 1.18, 95% CI 0.65 to 1.70; low-quality evidence) in favour of the combination therapy. Reports indicate that disease-specific QoL was comparable between groups (SMD 0.25, 95% CI -0.05 to 0.56; 2 studies; 330 participants; moderate-quality evidence) and that the number of secondary invasive interventions (OR 0.27, 95% CI 0.13 to 0.55; 3 studies; 457 participants; high-quality evidence) was lower following combination therapy.Two studies comparing endovascular revascularisation plus pharmacotherapy (cilostazol) versus pharmacotherapy alone provided data showing a small effect on MWD (SMD 0.38, 95% CI 0.08 to 0.68; 186 participants; high-quality evidence), a moderate effect on PFWD (SMD 0.63, 95% CI 0.33 to 0.94; 186 participants; high-quality evidence), and a moderate effect on disease-specific QoL (SMD 0.59, 95% CI 0.27 to 0.91; 170 participants; high-quality evidence) in favour of combination therapy. Long-term follow-up in one study (47 participants) revealed a moderate effect on MWD (SMD 0.72, 95% CI 0.09 to 1.36; P = 0.02) in favour of combination therapy and no clear differences in PFWD between groups (SMD 0.54, 95% CI -0.08 to 1.17; P = 0.09). The number of secondary invasive interventions was comparable between groups (OR 1.83, 95% CI 0.49 to 6.83; 199 participants; high-quality evidence). AUTHORS' CONCLUSIONS: In the management of patients with IC, endovascular revascularisation does not provide significant benefits compared with supervised exercise alone in terms of improvement in functional performance or QoL. Although the number of studies is small and clinical heterogeneity underlines the need for more homogenous and larger studies, evidence suggests that a synergetic effect may occur when endovascular revascularisation is combined with a conservative therapy of supervised exercise or pharmacotherapy with cilostazol: the combination therapy seems to result in greater improvements in functional performance and in QoL scores than are seen with conservative therapy alone.

Multidisciplinary treatment for peripheral arterial occlusive disease and the role of eHealth and mHealth.

Increasingly unaffordable health care costs are forcing care providers to develop economically viable and efficient health care plans. Currently, only a minority of all newly diagnosed peripheral arterial occlusive disease (PAOD) patients receive efficient and structured conservative treatment for their disease. The aim of this article is to introduce an innovative effective treatment model termed ClaudicatioNet. This concept was launched in The Netherlands as a means to combat treatment shortcomings and stimulate cohesion and collaboration between stakeholders. The overall goal of ClaudicatioNet is to stimulate quality and transparency of PAOD treatment by optimizing multidisciplinary health care chains on a national level. Improved quality is based on stimulating both a theoretical and practical knowledge base, while eHealth and mHealth technologies are used to create clear insights of provided care to enhance quality control management, in addition these technologies can be used to increase patient empowerment, thereby increasing efficacy of PAOD treatment. This online community consists of a web portal with public and personal information supplemented with a mobile application. By connecting to these tools, a social community is created where patients can meet and keep in touch with fellow patients, while useful information for supervising health care professionals is provided. The ClaudicatioNet concept will likely create more efficient and cost-effective PAOD treatment by improving the quality of supervised training programs, extending possibilities and stimulating patient empowerment by using eHealth and mHealth solutions. A free market principle is introduced by introducing transparency to provided care by using objective and subjective outcome parameters. Cost-effectiveness can be achieved using supervised training programs, which may substitute for or postpone expensive invasive vascular interventions.