Abstract Objectives Several systematic reviews have focused on the role of preoperative exercise therapy (PET) in various fields of surgical care. Aims of the present scoping review are to summarize ...research findings and to identify gaps in existing literature. Methods Two authors independently conducted a comprehensive literature search on systematic reviews regarding PET. The risk of bias was assessed using “the methodology checklist for systematic reviews and meta-analyses of the Scottish Intercollegiate Guidelines Network (SIGN).” Findings of the included systematic reviews were summarized according to type of surgery and type of PET. Results Twenty-one reviews on PET with a low risk of bias were included. Seven reviews investigated PET in multiple surgical fields and 14 in just a single surgical field. PET was studied before cardiac surgery (n = 9), orthopedic surgery (n = 8), abdominal surgery (n = 8), thoracic surgery (n = 8), vascular surgery (n = 3), and urologic surgery (n = 1). Conclusion Overall, it seems that PET exerts beneficial effects on physical fitness and postoperative outcome measures. Gaps in current literature are the heterogeneity in selected patient populations and outcome measures as well as lack of guidelines on the specific PET regimes. Therefore, there is increasing need for multicenter randomized trials with specifically designed PET programs and a carefully selected patient population to strengthen current evidence.
Background Walking capacity measured by a treadmill test (TT) reflects the patient's maximal capacity in a controlled setting and is part of the physical exercise capacity (PEC). Daily physical ...activity (PA) is defined as the total of actively freely produced movements per day. A lower PA level has been increasingly recognized as a strong predictor of increased morbidity and mortality in patients with intermittent claudication (IC). Recent insights suggested that an increased PEC does not automatically lead to an increase in daily PA. However, the precise relation between PEC and PA in patients with IC is still unclear. Methods A cross-sectional study was conducted to assess the association between several PEC outcomes and PA in a general IC population. PEC was determined by well-established tests (Gardner-Skinner TT, a physical performance battery, a timed up-and-go test, and a 6-minute walk test distance). PA was obtained during 7 consecutive days using a triaxial accelerometer (Dynaport MoveMonitor; McRoberts BV, The Hague, The Netherlands). Five PA components (lying, sitting, standing, shuffling, and locomotion) and four parameters (total duration, number of periods, mean duration per period, and mean movement intensity per period) were analysed. Correlation coefficients between PEC and PA components were calculated. Results Data of 46 patients were available for analysis. Patients were sedentary (sitting and lying) during 81% of the day and were physically active (standing, shuffling, and locomotion) for the remaining 19% of the time. Correlations between PEC outcomes and PA ranged from very weak (0.025) to moderate (0.663). Moderate correlations (as therefore assumed to be relevant) were only found for outcomes of both the TT and 6-minute walk test and the locomotion components of PA. For instance, functional claudication distance (measured by TT) and number of steps per day correlated reasonably well (Spearman correlation ρ = 0.663; P < .01). Conclusions Exercise capacity and PA correlate minimally in patients with IC. PA may be preferred as a novel outcome measure and future treatment target in patients with IC.
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.
The synthesis and in vitro structure−activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The ...compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52−72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.
Glycine amide inhibitors of human liver glycogen phosphorylase A with improved potency in vivo are reported.
The synthesis, in vitro, and in vivo biological characterization of a series of achiral ...5-chloroindoloyl glycine amide inhibitors of human liver glycogen phosphorylase A are described. Improved potency over previously reported compounds in cellular and in vivo assays was observed. The allosteric binding site of these compounds was shown by X-ray crystallography to be the same as that reported previously for 5-chloroindoloyl norstatine amides.
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose ...1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.
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