Complementary and Alternative Therapies for Back Pain II: Structured Abstract

Back Pain II, Complementary and Alternative Medicine
Full Title: Complementary and Alternative Therapies for Back Pain II

View or download Report, pdf, 764 pages:
http://www.ahrq.gov/downloads/pub/evidence/pdf/backpaincam/backcam2.pdf
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Structured Abstract
Background: Back and neck pain are important health problems with serious societal and economic implications. Conventional treatments have been shown to have limited benefit in improving patient outcomes. Complementary and Alternative Medicine (CAM) therapies offer additional options in the management of low back and neck pain. Many trials evaluating CAM therapies have poor quality and inconsistent results.

Objectives: To systematically review the efficacy, effectiveness, cost-effectiveness, and harms of acupuncture, spinal manipulation, mobilization, and massage techniques in management of back, neck, and/or thoracic pain.

Data Sources: MEDLINE®, Cochrane Central, Cochrane Database of Systematic Reviews, CINAHL, and EMBASE were searched up to 2010; unpublished literature and reference lists of relevant articles were also searched.

Study Selection: All records were screened by two independent reviewers. Primary reports of comparative efficacy, effectiveness, harms, and/or economic evaluations from randomized controlled trials (RCTs) of the CAM therapies in adults (age ≥ 18 years) with back, neck, or thoracic pain were eligible. Non-randomized controlled trials and observational studies (casecontrol, cohort, cross-sectional) comparing harms were also included. Reviews, case reports, editorials, commentaries or letters were excluded.

Data Extraction: Two independent reviewers using a predefined form extracted data on study, participants, treatments, and outcome characteristics.

Results: 265 RCTs and 5 non-RCTs were included. Acupuncture for chronic nonspecific low back pain was associated with significantly lower pain intensity than placebo but only immediately post-treatment (VAS: -0.59, 95 percent CI: -0.93, -0.25). However, acupuncture was not different from placebo in post-treatment disability, pain medication intake, or global improvement in chronic nonspecific low back pain. Acupuncture did not differ from sham-acupuncture in reducing chronic non-specific neck pain immediately after treatment (VAS: 0.24, 95 percent CI: -1.20, 0.73). Acupuncture was superior to no treatment in improving pain intensity (VAS: -1.19, 95 percent CI: 95 percent CI: -2.17, -0.21), disability (PDI), functioning (HFAQ), well-being (SF-36), and range of mobility (extension, flexion), immediately after the treatment. In general, trials that applied sham-acupuncture tended to produce negative results (i.e., statistically non-significant) compared to trials that applied other types of placebo (e.g., TENS, medication, laser). Results regarding comparisons with other active treatments (pain medication, mobilization, laser therapy) were less consistent Acupuncture was more cost-effective compared to usual care or no treatment for patients with chronic back pain.

For both low back and neck pain, manipulation was significantly better than placebo or no treatment in reducing pain immediately or short-term after the end of treatment. Manipulation was also better than acupuncture in improving pain and function in chronic nonspecific low back pain. Results from studies comparing manipulation to massage, medication, or physiotherapy were inconsistent, either in favor of manipulation or indicating no significant difference between the two treatments. Findings of studies regarding costs of manipulation relative to other therapies were inconsistent.

Mobilization was superior to no treatment but not different from placebo in reducing low back pain or spinal flexibility after the treatment. Mobilization was better than physiotherapy in reducing low back pain (VAS: -0.50, 95 percent CI: -0.70, -0.30) and disability (Oswestry: -4.93, 95 percent CI: -5.91, -3.96). In subjects with acute or subacute neck pain, mobilization compared to placebo significantly reduced neck pain. Mobilization and placebo did not differ in subjects with chronic neck pain.

Massage was superior to placebo or no treatment in reducing pain and disability only amongst subjects with acute/sub-acute low back pain. Massage was also significantly better than physical therapy in improving back pain (VAS: -2.11, 95 percent CI: -3.15, -1.07) or disability. For subjects with neck pain, massage was better than no treatment, placebo, or exercise in improving pain or disability, but not neck flexibility. Some evidence indicated higher costs for massage use compared to general practitioner care for low back pain.

Reporting of harms in RCTs was poor and inconsistent. Subjects receiving CAM therapies reported soreness or bleeding on the site of application after acupuncture and worsening of pain after manipulation or massage. In two case-control studies cervical manipulation was shown to be significantly associated with vertebral artery dissection or vertebrobasilar vascular accident.

Conclusions: Evidence was of poor to moderate grade and most of it pertained to chronic nonspecific pain, making it difficult to draw more definitive conclusions regarding benefits and harms of CAM therapies in subjects with acute/subacute, mixed, or unknown duration of pain. The benefit of CAM treatments was mostly evident immediately or shortly after the end of the treatment and then faded with time. Very few studies reported long-term outcomes. There was insufficient data to explore subgroup effects. The trial results were inconsistent due probably to methodological and clinical diversity, thereby limiting the extent of quantitative synthesis and complicating interpretation of trial results. Strong efforts are warranted to improve the conduct methodology and reporting quality of primary studies of CAM therapies. Future well powered head to head comparisons of CAM treatments and trials comparing CAM to widely used active treatments that report on all clinically relevant outcomes are needed to draw better conclusions.


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Complementary and Alternative Therapies for Back Pain II

•Evidence Report (Publication No. 10(11)-E007): (PDF File, 6.5 MB) PDF Help.
http://www.ahrq.gov/downloads/pub/evidence/pdf/backpaincam/backcam2.pdf
Current as of October 2010


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Internet Citation:

Complementary and Alternative Therapies for Back Pain II, Structured Abstract. October 2010. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/tp/backcam2tp.htm

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Complementary and Alternative Therapies for Back Pain II: Structured Abstract

Safety Alerts for Human Medical Products > Methotrexate Injection, 50mg/2mL and 250mg/10mL Vials: Recall - Presence of Glass Particulates

Methotrexate Injection, 50mg/2mL and 250mg/10mL Vials: Recall - Presence of Glass Particulates

AUDIENCE: Pharmacy, Risk Manager

ISSUE: Sandoz and FDA notified healthcare professionals of a recall of Methotrexate Injection, 50mg/2mL and 250mg/10mL vials, due to small glass flakes detected in a limited number of vials in four lots. The flakes are the result of delamination of the glass used to manufacture the vials of the two dosage presentations.

Parenteral injection of drug from the affected lots could lead to serious adverse events in areas where the particles lodge. Potential adverse events after intravenous administration include local damage to blood vessels in the lung, localized swelling, and granuloma formation. Intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling and possible long term granuloma formation. Neurologic damage could result from intrathecal administration.

BACKGROUND: Methotrexate is an antimetabolite used in the treatment of neoplastic diseases, severe psoriasis, and rheumatoid arthritis, including polyarticular juvenile rheumatoid arthritis.

RECOMMENDATION: Customers and patients should immediately discontinue use of this product and patients should contact their physician or healthcare provider if they experience any problem that might be related to the use of this product. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Product lot numbers, label type, expiration dates, and recall instructions are listed in the Press Release.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and
Adverse Event Reporting Program:
Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178


Read the MedWatch safety alert, including a link to the Press Release, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm231614.htm

Safety Alerts for Human Medical Products > Methotrexate Injection, 50mg/2mL and 250mg/10mL Vials: Recall - Presence of Glass Particulates

Inhaled Nitric Oxide in Preterm Infants: Structured Abstract

Inhaled Nitric Oxide in Preterm Infants
October 2010
View or download Report,pdf, 319 pages, 8.7MB
http://www.ahrq.gov/downloads/pub/evidence/pdf/inoinfants/inoinfants.pdf
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Structured Abstract
Objectives: To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support.

Data Sources: We searched MEDLINE®, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts.

Review Methods: Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles.

Results: We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies).

Conclusions: There was a seven-percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.


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Inhaled Nitric Oxide in Preterm Infants

•Evidence Report (Publication No. No. 11-E001): (PDF File, 8.7 MB) PDF Help
http://www.ahrq.gov/downloads/pub/evidence/pdf/inoinfants/inoinfants.pdf
Evidence-based Practice Center: Johns Hopkins University

Current as of October 2010


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Internet Citation:

Inhaled Nitric Oxide in Preterm Infants, Structured Abstract. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/tp/inoinftp.htm
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Inhaled Nitric Oxide in Preterm Infants: Structured Abstract

Promising New 'Antigene' Therapy

Promising New 'Antigene' Therapy
Main Category: Genetics
Article Date: 25 Oct 2010 - 0:00 PDT


Antigene therapy is a promising new treatment strategy that uses a DNA-based drug to pinpoint light energy to a target gene shutting down its activity. A review article published online ahead of print in Oligonucleotides, a peer-reviewed journal published by Mary Ann Liebert, Inc., details the possibilities and challenges for the clinical application of this novel photo-activated DNA modulating approach.

Netanel Kolevzon and Eylon Yavin, from The Hebrew University of Jerusalem (Israel), describe the mechanism behind antigene therapy in the article "Site-Specific DNA Photocleavage and Photomodulation by Oligonucleotide Conjugates." They review the development of triplex-forming DNA-based drugs capable of up-regulating or inhibiting gene expression in a highly targeted and selective manner.

Unlike existing antisense therapies that target RNA, an antigene drug is a triplex-forming oligonucleotide that recognizes and attaches directly to a specific DNA sequence. By attaching a photoreactive agent to the antigene and delivering light energy to the attachment site, the light-sensitive drug complex becomes activated, triggering a cleavage or cross-linking reaction. This photo-induced, site-specific DNA damage effectively silences the gene target.

"Many obstacles lay ahead before this approach may reach the clinic," caution the authors. However, if antigene therapy proves successful at blocking gene activity, "many diseases that are currently incurable or otherwise treatable with limited success could be potentially relevant targets for such an approach," they conclude.

"This is a clever and potentially powerful approach to targeted regulation of gene expression," says John Rossi, PhD, Co-Editor-in-Chief of Oligonucleotides and Professor in the Department of Molecular Biology, Beckman Research Institute of the City of Hope (Duarte, CA).

Oligonucleotides, edited by John Rossi, PhD, and C.A. Stein, MD, PhD, from the Department of Oncology at Albert Einstein-Montefiore Cancer Center, is an authoritative, peer-reviewed journal published 6 times a year in print and online that focuses on synthetic oligonucleotides, including RNA, DNA, and ribozymes, and their effects on gene expression at the RNA and DNA levels both in vitro and in vivo. It represents a forum for basic research and applied therapeutics for the purpose of developing new concepts and experimental approaches to understanding and modulating gene activity. Oligonucleotides is the Official Journal of the Oligonucleotide Therapeutics Society (http://www.myots.org). Tables of content and a free sample issue may be viewed online at http://www.liebertpub.com/oli

Source:
Julia Chapman
Mary Ann Liebert, Inc./Genetic Engineering News
Promising New 'Antigene' Therapy

Clear New Insights into the Genetics of Depression: Scientific American

Clear New Insights into the Genetics of Depression
Recent findings suggest novel paths to treatment

By Colm O'Dushlaine |October 26, 2010 | 10

According to the National Institute for Mental Health this “inability” can affect up to 14.8 million Americans – 7% of the population – in a given year, at an annual cost of $100 billion. That’s about five times the renewable energy budget of the United States. We hear many things about how great we’re getting at saving the planet with our hybrids and off-shore wind farms; we hear far less about how we’re doing in combating or preventing depression.

This month, however, has brought some potentially exciting news: two genetic studies with major ramifications for the treatment and diagnosis of Major Depressive Disorder. As a psychiatric geneticist, it is rare that I see such clear insights into distinct genetic mechanisms of psychiatric illnesses. Research into bipolar disorder and schizophrenia –- the disorders I spend most of my time working on –- would benefit a great deal from breakthrough studies such as these.

One new study, published in Nature Medicine, suggests that a pathway called MAPK – and one gene in particular from this pathway, MPK-1 – are significantly dysregulated in certain areas of the brains of individuals with major depression. These results were obtained by looking for significant gene expression changes in post-mortem brains from 21 individuals with Major Depressive Disorder compared to 18 matched controls.

The researchers, led by Yale’s Vanja Duric, confirmed their results in rat and mouse models. And they showed that not only did raising MPK-1 levels lead to depressive symptoms, but that antidepressant treatment reduced the expression of MPK-1.

They demonstrated that MPK-1 increases during stress and can negatively regulate MAPK, a key signaling pathway involved in neuronal plasticity, function and survival. In effect, it appears that MPK-1 may be important in depression because when too much of it is around, it disturbs the growth and viability of neurons in a part of the brain known as the hippocampus, a factor believed to contribute to symptoms of major depression.

Dr. Duric’s team conclude that developing drugs to regulate MPK-1 may offer new hope for alleviating depression and related mood disorders. Drugs take many years to develop and bring to market, but knowing the mechanisms and targets can greatly help to speed up the process. We know what sort of protein MPK-1 is and we know how it works, which makes drug development a lot simpler.

A second new study, published in “Science” and led by Brian Alexander of Cornell’s Laboratory of Molecular Neurosurgery, goes a step further by applying gene therapy to mutant mice. These mice were missing a gene, p11, the deletion of which has been shown to induce depression-like behavior. The p11 gene helps regulate the signaling of serotonin, a brain chemical targeted by many antidepressants and tied to mood, sleep and memory.

Dr. Alexander’s team found that using gene therapy – essentially using a virus to deliver a “working” copy of a gene into a host whose copy is defective or missing – to restore p11 expression in specific parts of the brain was able to decrease depression-like behavior.

This gene therapy approach is also being applied to Parkinson’s disease. Gene therapy offers the tantalizing possibility of a permanent treatment, eliminating the need for daily consumption of medications. This is an important point as many people do not take medications as they should. Others suffer from adverse drug reactions. With gene therapy, you get a drug that is completely natural: it is a gene; it is part of a prescription not for medication, but for building a healthy human.

The “Science” study helps give new life to the field of gene therapy, which itself was exhibiting depression-like symptoms. The idea of using gene therapy to replace defective DNA has been around since the 70’s, but suffered a large setback in 1999 with a subject’s death and subsequent suspension of several clinical trials for ethical reasons.

The MPK-1 findings point to a host of therapeutic interventions. Gene therapy may be one, as Alexander and colleagues demonstrated for p11. Characterizing the spectrum of mutations that modify the dysregulation of the pathway is another. The latter falls into the attractive realm of "pharmacogenomics" and the idea of “tailor-made” drugs, in this case antidepressants, which would be optimized for the genetics of a given individual.

It may not be long before the sequencing of our genome becomes a routine part of medicine, and from it could arise the automated optimization of drug treatments or lifestyle recommendations (such as: do not smoke if you are at exceptionally high risk of developing lung cancer). For depression, these advances will be greatly welcomed because even though anti-depressants may be highly effective, the rates of adverse drug reaction can be high. Also, patients’ responses to a given drug vary greatly. In the world of the future, a patient’s genetic profile could help suggest which drug would work best: Would Mr. Smith do best with a drug that targets p11? Or perhaps MPK-1?

The brain is an extremely complicated organ, with a myriad of complex loops and cycles of gene expression. It is likely that additional cascades of gene expression remain to be associated with susceptibility to depression. Genes in the MAPK pathway are unlikely to be the only “weak point” of susceptibility to the onset of Major Depressive Disorder, nor is p11. Nevertheless, every genetic mechanism for a disease that we discover is a possible path to novel pharmacological or behavioral interventions.

While there may well not be a “gene for depression”, we are quickly gaining a comprehensive, genetic understanding of the factors involved in this personally and socially crippling disorder. Depression is a prevalent, costly and harmful disorder which affects both the lives of individuals suffering from the disorder and their relatives. Finally, we may soon be in a position to help the many millions of Americans that suffer from depression to “construct a future” that is not plagued by the effects of this terrible illness.


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ABOUT THE AUTHOR(S)
Colm O'Dushlaine researches the genetics of psychiatry at Massachusetts General Hospital and The Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT.
Clear New Insights into the Genetics of Depression: Scientific American

ESHRE publishes new PGD guidelines

Contact: Hanna Hanssen
hanna@eshre.eu
322-263-6466
European Society of Human Reproduction and Embryology

ESHRE publishes new PGD guidelines

The four guidelines include one outlining the organisation of a PGD centre and three relating to the methods used: amplification-based testing, fluorescence in situ hybridisation (FISH)-based testing and polar body/embryo biopsy.

"The guidelines are a detailed update to the Consortium's initial PGD guidelines, published in the same journal in 2005. They have been developed as a set which, taken together, form a complete best-practice compendium," said Gary Harton, chairman of ESHRE's PGD Consortium and Head of Molecular Genetics at Reprogenetics in Livingston, New Jersey.

The rapid development of new technologies, the evolution of current methods and in light of recent advice from ESHRE on how best practice guidelines should be written, the PGD Consortium believed it necessary to update the existing guidelines.

The first guideline on the organisation of a PGD centre includes the basic requirements of an IVF/PGD centre, transport PGD (when the gametes and embryos to be tested are in a different centre than the patient), inclusion/exclusion criteria for patients, staffing, genetic counseling and accreditation of a centre.

The three more technical guidelines additionally cover laboratory requirements, clinical protocols and follow-up recommendations after diagnosis for each of the PGD methodologies: amplification-based testing, FISH-based testing and polar body/embryo biopsy.

The guidelines on amplification-based and FISH-based testing also outline quality control and quality assurance and the diagnostic confirmation of untransferred embryos. Freezing of embryos after biopsy is covered in the fourth guideline on the use of embryo biopsy in PGD/PGS.

Pre-implantation genetic screening (PGS) has been included in all guidelines. Although current evidence suggests it may be ineffective at the embryo cleavage stage using current technology, PGS may still show improved delivery rates if used at the blastocyst stage or on polar bodies. The ESHRE group decided deliberately to include PGS recommendations to assist every professional in the reproductive field to develop the best laboratory and clinical practice possible.


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All four papers on this research are published online in Human Reproduction journal today (Friday): doi: 10.1093/humrep/deq265

For more information contact: Hanna Hanssen, Communications Manager ESHRE, Tel: + 32 (0)2 263 64 66, Mob: +32 (0) 473 35 33 81, hanna@eshre.eu.

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ESHRE publishes new PGD guidelines

Pregnancy outcome affected by immune system genes

Contact: Karen Honey
press_releases@the-jci.org
734-546-5242
Journal of Clinical Investigation

Pregnancy outcome affected by immune system genes

A team of researchers, led by Ashley Moffett, at the University of Cambridge, United Kingdom, has shed new light on genetic factors that increase susceptibility to and provide protection from common disorders of pregnancy, specifically recurrent miscarriage, preeclampsia, and fetal growth restriction.

A key step in the initiation of a successful pregnancy is the invasion of the lining of the uterus by fetal cells known as trophoblasts, which become the main cell type of the placenta. Recurrent miscarriage, preeclampsia, and fetal growth restriction are thought to result from inadequate trophoblast invasion of the uterus lining. Interactions between maternal cells known as uterine NK cells and fetal trophoblasts — specifically interactions between HLA-C molecules on the fetal trophoblasts and KIRs on the maternal uterine NK cells — are key to determining the extent of trophoblast invasion. Previous data from Moffett's lab indicated that a particular combination of fetal HLA-C and maternal KIR was associated with increased risk of preeclampsia. In this study, the team has extended this correlation to recurrent miscarriage and fetal growth restriction. Furthermore, they have determined that the presence of other maternal KIRs that combine with the same HLA-C molecule provides protection against the same common disorders of pregnancy.

In an accompanying commentary, Peter Parham and Lisbeth Guethlein, at Stanford University, discuss the importance of these data and how they might explain distinct immune system gene expression patterns in different populations.


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TITLE: Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

AUTHOR CONTACT:
Ashley Moffett
University of Cambridge, Cambridge, United Kingdom.
Phone: 44.1223.333729; Fax: 44.1223.765065; E-mail: am485@cam.ac.uk.

View this article at: http://www.jci.org/articles/view/43998?key=cfb4e33703c44a22516f

ACCOMPANYING COMMENTARY
TITLE: Pregnancy immunogenetics: NK cell education in the womb?

AUTHOR CONTACT:
Peter Parham
Stanford University, Stanford, California, USA.
Phone: 650.723.7456; Fax: 650.723.8464; E-mail: peropa@stanford.edu.

View this article at: http://www.jci.org/articles/view/44559?key=a12c31691937fa2e1d6b

Pregnancy outcome affected by immune system genes