What is the most cost-effective treatment for patients with low back pain? A systematic review

Economic evaluations of the various interventions available for low back pain will help clinicians and policymakers to identify the most beneficial treatment. This chapter aims to evaluate the most cost-effective treatments for patients with non-specific low back pain. Pubmed, Embase and the Cochrane library were used to search for articles published from 1966 to July 2004 using a variety of keywords. References were checked to identify additional studies. The consensus health economic criteria (CHEC) list was used to assess the methodological quality of the studies. We found 17 studies; six of these concluded that the intervention of interest was superior to the control intervention. However, definite conclusions about the most cost-effective intervention could not be drawn because of the heterogeneity of interventions, controls and study populations. More high-quality economic evaluations are needed before such a conclusion can be made.     

Rapid molecular characterization of mutations leading to unstable hemoglobin β-chain variants

Summary Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable -chain variants, which produce a -thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the -globin gene. We describe the use of the DGGE method for rapid characterization of -chain variants and report a new missense mutation in the -globin gene third exon, 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin.     

Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception?

Summary In this study evidence is provided to suggest that nucleoside formation with hypoxia in myocardial tissue from the guinea-pig follows a different course from that in the rat, rabbit or dog. 1) After ischemia, tissue levels of adenosine remain barcly detectable in the guinea-pig but rise considerably in the rat and the dog. 2) IMP, remaining almost absent in the dog, does not change in the rat but strongly increases (×6) in the guinea-pig heart with ischemia. 3) Mioflazine, a nucleoside transport inhibitor, completely reverses the ratio adenosine/inosine in dog myocardium after 8 min of ischemia, making adenosine by far the major nuclcoside. No effect could be detected in the guinea-pig. 4) In contrast with the rat and rabbit, ischemia in the guinea-pig does not lead to any considerable release of adenosine upon reperfusion. 5) In the rabbit, the presence of a nucleoside transport inhibitor completely reverses the adenosine/inosine ratio in reperfusates after ischemia. Although the release is strongly inhibited under these conditions in the guinea-pig, adenosine release remains negligible when compared with inosine. 6) Even in the presence of high concentrations of an adenosine deaminase inhibitor, inosine remains the major metabolite released upon reperfusion after ischemia, in the guinea-pig heart.     

Carbon dioxide inhalation as a human experimental model of panic: The relationship between emotions and cardiovascular physiology

Inhaling carbon dioxide (CO₂)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO₂, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.5, and 35% CO₂, according to a randomized, cross-over design. In addition to fear, discomfort, and panic symptom ratings, blood pressure and heart rate were continuously monitored. Results showed a dose-dependent increase in all self-reports. Systolic and diastolic blood pressure rose with increasing CO₂ concentration, whereas heart rate results were less consistent. Diastolic blood pressure and heart rate variation correlated with fear and discomfort. Based on this relationship and the observation that the diastolic blood pressure most accurately mimicked the degree of self-reported emotions, it might serve as a putative biomarker to assess the CO₂-reactivity in the future.     

The Control of Silica Nanoparticles on the Phase Separation of Poly(methyl methacrylate)/Poly(styrene‐co‐acrylonitrile) Blends

The influence of silica nanoparticles on the lower critical solution temperature (LCST) phase behavior and phase‐separation kinetics of a blend consisting of poly(methyl methacrylate) (PMMA) and poly(styrene‐co‐acrylonitrile) (SAN), is studied via a high‐throughput experimentation (HTE) approach, which combines a composition (φ) and a temperature (T) gradient. The evolution of the phase‐separation process is studied by optical microscopy (OM), small‐angle light scattering (SALS), and transmission electron microscopy (TEM). Depending on the specific interaction between the silica surface and the polymers, the distribution of silica particles during phase separation can be controlled to be either in one of the polymer phases or at the PMMA/SAN interface. The hydrophilic silica nanoparticles preferentially migrate to the PMMA phase, leading to a slow down of the coarsening rate, which may be related to a reduction of the mobility of PMMA due to an increase of the silica concentration. The hydrophobic silica nanoparticles are localized at the PMMA/SAN interface, and the inhibition of coalescence corresponds to the presence of a solid barrier (the nanoparticles) between the polymers, which prevents the coarsening process.

     

The effect of promoter strength in adenoviral vectors in hyperplastic synovium

OBJECTIVES: To compare the activity of the CytoMegaloVirus promoter (CMV) and the Major Late promoter (MLP) in synoviocytes in vitro and in vivo. To determine the phenotype of infected cells and the induction of inflammation. To investigate the effects of the cytomegalovirus (CMV) or major late (MLP) promoter on adenovirus-mediated reporter gene transduction of synoviocytes in vitro and in vivo. METHODS: After infection with adenoviral vectors harboring CMV- and MLP-driven luciferase and lacZ genes, gene expression was examined in cultured synoviocytes and in the synovium of rhesus monkeys with collagen-induced arthritis. Immunohistochemical staining for the macrophage-marker CD68 and lacZ expression was performed. Inflammation was scored in the synovial membrane of injected and non-injected joints. RESULTS: CMV-driven reporter gene expression was found to be 6 to 10 times higher than MLP-driven gene expression in both cultured synoviocytes and monkey synovium. Both CD68 positive and CD68 negative cells were lacZ positive. Inflammation in joints injected with CMV-driven adenoviral vectors was not higher than that in MLP-driven adenoviral vectors- or non-injected joints. CONCLUSION: These experiments show that the CMV promoter induces higher gene expression in synoviocytes than the MLP promoter. Both fibroblast-like and macrophage-like synoviocytes can be infected with adenoviral vectors. No deleterious effects of the CMV-promoter driven adenoviral vectors were observed.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups

Background

Antibiotics are of limited overall clinical benefit for uncomplicated lower respiratory tract infection (LRTI) but there is uncertainty about their effectiveness for patients with features associated with higher levels of antibiotic prescribing.

Aim

To estimate the benefits and harms of antibiotics for acute LRTI among those producing coloured sputum, smokers, those with fever or prior comorbidities, and longer duration of prior illness.

Design and setting

Secondary analysis of a randomised controlled trial of antibiotic placebo for acute LRTI in primary care.

Method

Two thousand and sixty-one adults with acute LRTI, where pneumonia was not suspected clinically, were given amoxicillin or matching placebo. The duration of symptoms, rated moderately bad or worse (primary outcome), symptom severity on days 2–4 (0–6 scale), and the development of new or worsening symptoms were analysed in pre-specified subgroups of interest. Evidence of differential treatment effectiveness was assessed in prespecified subgroups by interaction terms.

Results

No subgroups were identified that were significantly more likely to benefit from antibiotics in terms of symptom duration or the development of new or worsening symptoms. Those with a history of significant comorbidities experienced a significantly greater reduction in symptom severity between days 2 and 4 (interaction term −0.28, P = 0.003; estimated effect of antibiotics among those with a past history −0.28 [95% confidence interval = −0.44 to −0.11], P = 0.001), equivalent to three people in 10 rating symptoms as a slight rather than a moderately bad problem. For subgroups not specified in advance antibiotics provided a modest reduction in symptom severity for non-smokers and for those with short prior illness duration (<7 days), and a modest reduction in symptom duration for those with short prior illness duration.

Conclusion

There is no clear evidence of clinically meaningful benefit from antibiotics in the studied high-risk groups of patients presenting in general practice with uncomplicated LRTIs where prescribing is highest. Any possible benefit must be balanced against the side-effects and longer-term effects on antibiotic resistance.