Although low-back pain is a highly prevalent condition, its clinical course remains uncertain. Our main objective was to systematically review the literature on the clinical course of pain and ...disability in patients with acute and persistent low-back pain. Our secondary objective was to investigate whether pain and disability have similar courses.
We performed a meta-analysis of inception cohort studies. We identified eligible studies by searching MEDLINE, Embase and CINAHL. We included prospective studies that enrolled an episode-inception cohort of patients with acute or persistent low-back pain and that measured pain, disability or recovery. Two independent reviewers extracted data and assessed methodologic quality. We used mixed models to determine pooled estimates of pain and disability over time.
Data from 33 discrete cohorts (11 166 participants) were included in the review. The variance-weighted mean pain score (out of a maximum score of 100) was 52 (95% CI 48-57) at baseline, 23 (95% CI 21-25) at 6 weeks, 12 (95% CI 9-15) at 26 weeks and 6 (95% CI 3-10) at 52 weeks after the onset of pain for cohorts with acute pain. Among cohorts with persistent pain, the variance-weighted mean pain score (out of 100) was 51 (95% CI 44-59) at baseline, 33 (95% CI 29-38) at 6 weeks, 26 (95% CI 20-33) at 26 weeks and 23 (95% CI 16-30) at 52 weeks after the onset of pain. The course of disability outcomes was similar to the time course of pain outcomes in the acute pain cohorts, but the pain outcomes were slightly worse than disability outcomes in the persistent pain cohorts.
Patients who presented with acute or persistent low-back pain improved markedly in the first six weeks. After that time improvement slowed. Low to moderate levels of pain and disability were still present at one year, especially in the cohorts with persistent pain.
Background
Non‐specific low back pain (LBP) is a common condition. It is reported to be a major health and socioeconomic problem associated with work absenteeism, disability and high costs for ...patients and society. Exercise is a modestly effective treatment for chronic LBP. However, current evidence suggests that no single form of exercise is superior to another. Among the most commonly used exercise interventions is motor control exercise (MCE). MCE intervention focuses on the activation of the deep trunk muscles and targets the restoration of control and co‐ordination of these muscles, progressing to more complex and functional tasks integrating the activation of deep and global trunk muscles. While there are previous systematic reviews of the effectiveness of MCE, recently published trials justify an updated systematic review.
Objectives
To evaluate the effectiveness of MCE in patients with chronic non‐specific LBP.
Search methods
We conducted electronic searches in CENTRAL, MEDLINE, EMBASE, five other databases and two trials registers from their inception up to April 2015. We also performed citation tracking and searched the reference lists of reviews and eligible trials.
Selection criteria
We included randomised controlled trials (RCTs) that examined the effectiveness of MCE in patients with chronic non‐specific LBP. We included trials comparing MCE with no treatment, another treatment or that added MCE as a supplement to other interventions. Primary outcomes were pain intensity and disability. We considered function, quality of life, return to work or recurrence as secondary outcomes. All outcomes must have been measured with a valid and reliable instrument.
Data collection and analysis
Two independent review authors screened the search results, assessed risk of bias and extracted the data. A third independent review author resolved any disagreement. We assessed risk of bias using the Cochrane Back and Neck (CBN) Review Group expanded 12‐item criteria. We extracted mean scores, standard deviations and sample sizes from the included trials, and if this information was not provided we calculated or estimated them using methods recommended in the Cochrane Handbook. We also contacted the authors of the trials for any missing or unclear information. We considered the following time points: short‐term (less than three months after randomisation); intermediate (at least three months but less than 12 months after randomisation); and long‐term (12 months or more after randomisation) follow‐up. We assessed heterogeneity by visual inspection of the forest plots, and by calculating the Chi2 test and the I2 statistic. We combined results in a meta‐analysis expressed as mean difference (MD) and 95% confidence interval (CI). We assessed the overall quality of the evidence using the GRADE approach.
Main results
We included 29 trials (n = 2431) in this review. The study sample sizes ranged from 20 to 323 participants. We considered a total of 76.6% of the included trials to have a low risk of bias, representing 86% of all participants. There is low to high quality evidence that MCE is not clinically more effective than other exercises for all follow‐up periods and outcomes tested. When compared with minimal intervention, there is low to moderate quality evidence that MCE is effective for improving pain at short, intermediate and long‐term follow‐up with medium effect sizes (long‐term, MD –12.97; 95% CI –18.51 to –7.42). There was also a clinically important difference for the outcomes function and global impression of recovery compared with minimal intervention. There is moderate to high quality evidence that there is no clinically important difference between MCE and manual therapy for all follow‐up periods and outcomes tested. Finally, there is very low to low quality evidence that MCE is clinically more effective than exercise and electrophysical agents (EPA) for pain, disability, global impression of recovery and quality of life with medium to large effect sizes (pain at short term, MD –30.18; 95% CI –35.32 to –25.05). Minor or no adverse events were reported in the included trials.
Authors' conclusions
There is very low to moderate quality evidence that MCE has a clinically important effect compared with a minimal intervention for chronic low back pain. There is very low to low quality evidence that MCE has a clinically important effect compared with exercise plus EPA. There is moderate to high quality evidence that MCE provides similar outcomes to manual therapies and low to moderate quality evidence that it provides similar outcomes to other forms of exercises. Given the evidence that MCE is not superior to other forms of exercise, the choice of exercise for chronic LBP should probably depend on patient or therapist preferences, therapist training, costs and safety.
Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral ...activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family.
Understanding the clinical course of low back pain is essential to informing treatment recommendations and patient stratification. Our aim was to update our previous systematic review and ...meta-analysis to gain a better understanding of the clinical course of acute, subacute and persistent low back pain.
To update our 2012 systematic review and meta-analysis, we searched the Embase, MEDLINE and CINAHL databases from 2011 until January 2023, using our previous search strategy. We included prospective inception cohort studies if they reported on participants with acute (< 6 wk), subacute (6 to less than 12 wk) or persistent (12 to less than 52 wk) nonspecific low back pain at study entry. Primary outcome measures included pain and disability (0-100 scale). We assessed risk of bias of included studies using a modified tool and assessed the level of confidence in pooled estimates using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We used a mixed model design to calculate pooled estimates (mean, 95% confidence interval CI) of pain and disability at 0, 6, 12, 26 and 52 weeks. We treated time in 2 ways: time since study entry (inception time uncorrected) and time since pain onset (inception time corrected). We transformed the latter by adding the mean inception time to the time of study entry.
We included 95 studies, with 60 separate cohorts in the systematic review (
= 17 974) and 47 cohorts (
= 9224) in the meta-analysis. Risk of bias of included studies was variable, with poor study attrition and follow-up, and most studies did not select participants as consecutive cases. For the acute pain cohort, the estimated mean pain score with inception time uncorrected was 56 (95% CI 49-62) at baseline, 26 (95% CI 21-31) at 6 weeks, 22 (95% CI 18-26) at 26 weeks and 21 (95% CI 17-25) at 52 weeks (moderate-certainty evidence). For the subacute pain cohort, the mean pain score was 63 (95% CI 55-71) at baseline, 29 (95% CI 22-37) at 6 weeks, 29 (95% CI 22-36) at 26 weeks and 31 (95% 23-39) at 52 weeks (moderate-certainty evidence). For the persistent pain cohort, the mean pain score was 56 (95% CI 37-74) at baseline, 48 (95% CI 32-64) at 6 weeks, 43 (95% CI 29-57) at 26 weeks and 40 (95% CI 27-54) at 52 weeks (very low-certainty evidence). The clinical course of disability was slightly more favourable than the clinical course of pain.
Participants with acute and subacute low back pain had substantial improvements in levels of pain and disability within the first 6 weeks ( moderate-certainty evidence); however, participants with persistent low back pain had high levels of pain and disability with minimal improvements over time (very low-certainty evidence). Identifying and escalating care in individuals with subacute low back pain who are recovering slowly could be a focus of intervention to reduce the likelihood of transition into persistent low back pain.
PROSPERO - CRD42020207442.
Abstract Pain self-efficacy and fear of movement have been proposed to explain how pain can lead to disability for patients with chronic low back pain. However the extent to which pain self-efficacy ...and fear of movement mediate the relationship between pain and disability over time has not been investigated. This study aimed to investigate whether pain self-efficacy and/or fear of movement mediate the relationship between pain intensity and disability in patients with recent onset chronic low back pain. In a two-wave longitudinal design, 184 chronic low back pain patients completed measures for pain intensity, disability, pain self-efficacy and fear of movement at baseline and 12 months after the onset of chronic low back pain. Regression analyses were used to test the mediational hypothesis. We found that, when measured at the same time, both pain self-efficacy and fear of movement beliefs partially mediated the effects of pain intensity on disability at the onset of chronic low back pain. However, in the longitudinal analyses, only improvements in self-efficacy beliefs partially mediated the relationship between changes in pain and changes in disability over a 12 months period. We found no support for the theory that fear of movement beliefs mediate this relationship. Therefore, we concluded that pain self-efficacy may be a more important variable than fear of movement beliefs in terms of understanding the relationship between pain and disability.
Arylidene indanone (AI) scaffolds are considered as the rigid cousins of chalcones, incorporating the α,β-unsaturated ketone system of chalcones forming a cyclic 5 membered ring. They are generally ...synthesized from 1-indanone and benzaldehydes
via
an aldol reaction. The furnished molecules have been explored as inhibitors of cholinesterases towards the treatment of Alzheimer's disease, as tubulin depolymerizing agents, as inhibitors of breast cancer and leukemia, inhibitors of dual specificity phosphatase (DUSP), as antimalarials, and for many other uses. This review is an effort to highlight the biochemical effects of arylidene indanones designed from natural or known drug compounds, discuss their structure-activity relationships (SAR), and correlate them with related chalcones providing insights for further development of this scaffold.
Arylidene indanone (AI) scaffolds are considered as the rigid cousins of chalcones, incorporating the α,β-unsaturated ketone system of chalcones forming a cyclic 5 membered ring.
This paper reports how the Quality by Design (QbD) principles can be applied to an existing industrial pharmaceutical fluid bed granulation process, using a three-step approach. Process analytical ...technology was implemented and the data generated treated with multivariate data analysis techniques. First, the variability of the industrial process was investigated, generating new process knowledge. Second, designed experiments were performed at a pilot scale to investigate the process response to changes in the Critical Process Parameters (CPPs). Finally, a Design Space (DS) for the process was defined, linking CPP to Critical to Quality Attributes (CQAs) of the granules, and after scale-up enabling its use at the industrial scale. Within the DS, it is assured the desired quality of the granules consistently. Display omitted
The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale.
The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described.
•Two models for estimating small power consumption and demand profiles are presented.•Predictions of energy consumption correlate well with metered data for both models.•Prediction ranges for power ...demand profiles are representatives of metered data.•Both models provide an improved method for predicting small power performance.
Small power is a substantial energy end-use in office buildings in its own right, but also significantly contributes to internal heat gains. Technological advancements have allowed for higher efficiency computers, yet current working practices are demanding more out of digital equipment. Designers often rely on benchmarks to inform predictions of small power consumption, power demand and internal gains. These are often out of date and fail to account for the variability in equipment speciation and usage patterns in different offices. This paper details two models for estimating small power consumption in office buildings, alongside typical power demand profiles. The first model relies solely on the random sampling of monitored data, and the second relies on a ‘bottom-up’ approach to establish likely power demand and operational energy use. Both models were tested through a blind validation demonstrating a good correlation between metered data and monthly predictions of energy consumption. Prediction ranges for power demand profiles were also observed to be representative of metered data with minor exceptions. When compared to current practices, which often rely solely on the use of benchmarks, both proposed methods provide an improved approach to predicting the operational performance of small power equipment in offices.
Flight hampers the evolution of weapons in birds Menezes, João C. T.; Palaoro, Alexandre V.; Mooers, Arne
Ecology letters,
March 2022, 2022-Mar, 2022-03-00, 20220301, Letnik:
25, Številka:
3
Journal Article
Recenzirano
Birds are a remarkable example of how sexual selection can produce diverse ornaments and behaviours. Specialised fighting structures like deer's antlers, in contrast, are mostly absent among birds. ...Here, we investigated if the birds’ costly mode of locomotion—powered flight—helps explain the scarcity of weapons among members of this clade. Our simulations of flight energetics predicted that the cost of bony spurs—a specialised avian weapon—should increase with time spent flying. Bayesian phylogenetic comparative analyses using a global spur dataset corroborated this prediction. First, extant species with flight‐efficient wings (which presumably fly more frequently) tend to have fewer or no bony spurs. Second, this association likely arose because flying more leads to more frequent evolutionary loss of spurs. Together, these findings suggest that, much like pneumatic bones, absence of weaponry may be another feature of the avian body plan that allows birds to efficiently explore the aerial habitat.
Birds are remarkable for their diverse colours, songs, ornaments and displays, but not for their weapons. Here, we show that their costly mode of locomotion—flight—helps explain that. Bird species that depend more on flight possess on average fewer or no bony spurs, likely because these specialised weapons are often too costly to carry in flight.
Summary
Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now ...considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and thus influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies has led to the hypothesis that the indeterminate form is associated with an anti‐inflammatory cytokine profile, represented by high expression of IL‐10, while cardiac form is associated with a high production of IFN‐gamma and TNF‐alpha in relation to IL‐10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.
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