The prognosis of acute and persistent low-back pain: a meta-analysis

Background:

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.

Methods:

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.

Results:

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.

Interpretation:

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.Low-back pain is a highly prevalent condition associated with work absenteeism, disability and large health care costs; however, there is still disagreement about prognosis. For example, the European guidelines for the management of low-back pain states that 90% of patients with acute low-back pain recover in six weeks.¹ In contrast, some well-conducted cohort studies show a less optimistic picture, providing short-term estimates of recovery ranging from 39% to 76%.^2,3 This wide range of estimates of prognosis is likely explained by differences in cohorts and definitions used to define the onset or conclusion of an episode of low-back pain. Because very different definitions of recovery are often used, it is difficult to obtain pooled estimates of recovery rates. Instead, it might be more useful to describe the clinical course of low-back pain in terms of expected changes in pain or disability over time.A recent systematic review⁴ summarized the prognostic factors for persistent disabling low-back pain but did not describe the clinical course. The only meta-analysis to investigate the clinical course of acute low-back pain was published in 2003.⁵ This review concluded that both pain and disability improve rapidly within weeks (mean reduction of 58% of initial scores in the first month) and recurrences are common. A limitation of this review was that, although it retrieved 15 studies, only 5 were cohort studies; the remaining 10 were randomized controlled trials. Randomized trials often have narrow inclusion criteria and low rates of participation, which make them less suitable for inferring prognosis. The best design to describe the prognosis of a condition is a cohort study enrolling a representative sample of incident cases (i.e., by including patients at a similar early point in their condition).^6,7 Such studies are known as inception cohort studies. To the best of our knowledge, no review has yet investigated the clinical course of pain and disability among people with persistent low-back pain (subacute and chronic). Thus, the prognosis for people with persistent low-back pain is still uncertain.The aim of our study was to systematically review the clinical course of pain and disability in patients with acute and persistent low-back pain. We included only inception cohort studies. Our second aim was to investigate whether pain and disability have similar courses.     

Annotated list of demersal fishes occurring at Sedlo Seamount, Azores north-east central Atlantic Ocean

Several fish surveys were carried out in recent years at Sedlo Seamount, Azores, north-eastern central Atlantic Ocean. An objective of the surveys was to determine the species composition of the demersal fish species living in the area. Four types of sampling gears (bottom trawl and three types of longline) were used at Sedlo Seamount resulting in very different species composition by gear and a very complete coverage of the fish fauna of the area. A list of fishes caught with these sampling methods is presented, along with other specific auxiliary information. Altogether 78 species from 43 families were listed for Sedlo Seamount, and as far as is known, 15 species were recorded for the first time for Azorean waters.     

Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.     

Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case–control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5′-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.     

Hepatitis C virus quantification in serum and saliva of HCV-infected patients

The hepatitis C virus (HCV) can be detected in blood and other bodily fluids, such as saliva, semen and gastric juices. The aim of this study was to compare the HCV viral loads in the serum and saliva of infected patients. Twenty-nine patients with detectable HCV RNA in their serum and saliva were included in this study. The HCV viral loads were determined through quantitative real-time polymerase chain reactions. The median viral RNA levels were 5.78 log10 copies in the serum and 3.32 log10 copies in the saliva. We observed that the salivary HCV viral load was significantly lower than the viral load in the serum. Further studies are required to understand the role of saliva in the diagnosis, management and potential transmission of HCV.     

<Emphasis Type="Italic">Cabruca</Emphasis> agroforests in southern Bahia,Brazil: tree component,management practices and tree species conservation

In southern Bahia, Brazil, cabrucas are the traditional agroforests in which cacao trees are planted under thinned-out native forests. To analyze the role of cabrucas in tree species conservation, we inventoried the non-cocoa trees in 1.0 ha plots of cabruca in 16 cocoa farms and compared our results with a similar survey undertaken in the early 1960s in the same region to analyze the long term changes. We also interviewed 160 cocoa farmers to investigate their preferences for species and the main practices used in managing shade trees. The cabrucas showed high levels of tree diversity for an agroforestry system (Shannon index ranging from 2.21 to 3.52) and also high variation in structure and composition among the different farms. Forest specialist trees accounted for most species (63.9%) in the survey and were among the species most preferred by the farmers, although we found evidence that some of these trees are gradually being replaced by other species. Our results indicate that cabrucas are poor substitutes for undisturbed forests in terms of tree species richness, but their presence in human-altered landscapes is of utmost importance to the conservation of forest tree species as they increase overall heterogeneity and may serve as ecological corridors, additional habitats, and buffer zones.     

Pivotal role of inosine triphosphate pyrophosphatase in maintaining genome stability and the prevention of apoptosis in human cells

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer.     

A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection

There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection.