In a study led by Cancer Research UK, researchers in Scotland have demonstrated that a nurse-led intervention, termed Depression Care for People with Cancer, designed to treat major depressive disorder in cancer patients, is successful not only at reducing depressive symptoms, but also improved anxiety and fatigue.
A total of 200 cancer patients who suffered from clinical depression were randomly assigned to receive standard NHS treatment (n = 99) or standard treatment plus Depression Care for People with Cancer (DCPC; n = 101) in the study published in The Lancet.
Those who were assigned to DCPC received an average of seven one-to-one sessions with a specialist cancer nurse. The sessions were designed to help the patients understand depression and the effects of antidepressants, and included problem-solving therapy, and liaison with their oncologist and GP to collaborate in treating the depression, as well as monthly monitoring via telephone with the option of additional booster sessions if necessary.
At 3 months, nearly 20% fewer patients in the DCPC group were depressed compared with those receiving standard treatment. The effect was also shown to be sustained at both 6 and 12 months. The primary outcome was the difference in mean score on the self-reported Symptom Checklist 20 depression scale.
Michael Sharpe, lead author of the study, explained, “10% of cancer patients experience clinical depression and it is not always adequately treated. This new treatment could substantially improve the way we manage depression in people with cancer, and also in people with other serious medical conditions. This is the first time that this type of depression treatment has been evaluated in cancer patients and the results are encouraging.”
Cancer Research UK recently reported that although the number of cases of cancer had increased since the NHS was founded 60 years ago, the number of people surviving the most common types of cancer for at least 5 years had doubled. With this increase in cancer diagnoses and survival rates, improved treatment of cancer-associated depression will be invaluable in improving the quality of life of depressed cancer sufferers.
Sources: Strong V, Waters R, Hibberd C et al. Management of depression for people with cancer (SMaRT oncology 1): a randomised trial. Lancet 372, 40–48 (2008);
Cancer Research UK Press Release: Cancer cases up but survival more than doubles in breast and bowel cancer. 2008. http://info.cancerresearchuk.org/news/archive/pressreleases/2008/july/445723
Neonates often do not receive adequate pain relief
Study reveals a shockingly small amount of newborns receive pain medication in intensive care units.
Published in the July issue of JAMA, researchers from France and the USA found that only 2% of 430 babies received pain medication and 18.2% nonpharmacological therapy in intensive care units (ICUs) in the Paris area between September 2005 and January 2006.
The babies were, on average, almost 2 months premature, and had an average stay in ICU of 8.4 days. During this time, the 430 babies received a total of 60,969 first-attempt procedures. Of these procedures, 42,413 were classed as painful and 18,556 stressful. On average, each baby underwent 141 procedures.
“We found that babies are exposed to a lot of painful and stressful procedures, mostly not treated with pain-relieving interventions,” commented Ricardo Carbajal, Professor of Pediatrics and Chief of the National Center of Resources to Fight Pain at Children’s Hospital Armand Trousseau (Paris, France).
The authors highlighted that it is particularly important to improve pain relief in neonates because they are more sensitive to pain and because there is a risk that this early pain may alter the way their brains process pain.
“Multiple lines of evidence suggest that repeated and prolonged pain exposure alters [newborn infants’] subsequent pain processing, long-term development, and behavior,” explained Carbajal and colleagues. “It is essential, therefore, to prevent or treat pain in neonates.”
The authors suggested that this lack of adequate pain relief may be due to concerns regarding possible side effects, the lack of standardized procedures or the lack of specific analgesics for the relief of pain in newborns. They recommend that, where possible, procedures should be performed in combination, and that nonpharmacological pain-reducing methods should be used.
Source: Carbajal R, Rousset A, Danan C et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA 300(1), 60–70 (2008).
Potential risk of long-term statin use
Recent research suggests long-term use of statins may have detrimental effects on the brain
Published in the July issue of Glia, researchers from the University of Rochester Medical Center (NY, USA) have demonstrated that statins may effect the lineage commitment of glial progenitor cells (GPCs). Statins are currently widely prescribed for a variety of disorders, including cardiovascular disease, stroke and diabetes.
A genomic screen was performed to identify genes that are more active in GPCs compared with other brain cells. Interestingly, the researchers found several genes related to the sterol synthesis pathway, including HMG-CoA reductase, the principal target of statins, were highly active in the cells.
“It was quite surprising that the cholesterol-signaling pathways are so active in these cells,” commented Steven Goldman, coauthor of the study. “Since such signaling is blocked with compounds used literally by millions of patients every day, we decided to take a closer look.”
The researchers then went on to test the effects of the statins simvastatin and pravastatin on human GPCs. GPCs have the ability to differentiate into either astrocytes or oligodendrocytes. However, both simvastatin and pravastatin caused many GPCs to develop into oligodendrocyes, thus reducing the number of GPCs.
“These are the cells ready to respond if you have a region of the brain that is damaged due to trauma, or lack of blood flow like a mini-stroke,” commented Fraser Sim, coauthor of the study. “Researchers need to look very carefully at what happens if these cells have been depleted prematurely.”
The authors noted that their results highlight that further research to investigate the effects of long-term statin use is required. “Our results suggest the need for awareness of the possible toxicities accruing to long-term statin use, and identify one such potential toxicity, the premature differentiation and attendant long-term depletion of oligodendrocyte progenitor cells of the adult brain,” they concluded in the paper.
Steven Goldman stressed that research was at an early stage, and that a great deal more work was required to understand the complex role of statins in disorders such as dementia.
“There has been a great deal of discussion about a link between statins and dementia, but evidence either way has been scant,” he commented. “These new data provide a basis for further exploration. These findings were made through experiments done in cell culture using human brain cells and exposing them to doses of statins used widely in patients. But this research was not done in people. There are a great number of questions that need to be explored further before anyone considers changing the way statins are used.
Source: Sim FJ, Lang JK, Ali TA et al. Statin treatment of adult human glial progenitors induces PPARα-mediated oligodendrocytic differentiation. Glia 56(9), 954–962 (2008).
Overexpression of a single gene is able to alter neuronal fate
Published online ahead of print in Nature Neuroscience, researchers from the Salk Institute for Biological Studies (CA, USA) and the Swiss Federal Institute of Technology (Zurich, Switzerland) have successfully redirected the fate of newborn cells in the dentate gyrus of mice in vivo.
“When we grow stem cells in the lab, we add lots of growth factors resulting in artificial conditions, which might not tell us a lot about the in vivo situation,” explained Sebastian Jessberger, Assistant Professor at the Swiss Federal Institute of Technology. “As a result we don’t know much about the actual plasticity of neural stem cells within their adult brain niche.”
The researchers used retroviruses to overexpress the gene Ascl1. In normal circumstances, the majority of newborn cells differentiate into neurons. However, when Ascl1 was overexpressed, oligodendrocytic cells were generated rather than neurons.
“We have known that the birth and death of adult stem cells in the brain could be influenced be experience, but we were surprised that a single gene could change the fate of stem cells in the brain,” commented the lead author of the study, Fred Gage.
The authors hope that further research in this area may lead to potential novel therapeutics for neurological disorders such as stroke, epilepsy and multiple sclerosis. “These data indicate that adult hippocampal stem/progenitor cells (AHPs) have substantial plasticity, which might have important implications for the potential use of endogenous AHPs in neurological disease,” they concluded.
Source: Jessberger S, Toni N, Clemenson Jr GD, Ray J, Gage FH. Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nat. Neurosci. (Epub ahead of print).
Higher dose of glatiramer acetate not more effective for treatment of multiple sclerosis
Drug: Glatiramer acetate
Maufacturer: Teva Pharmaceutical Industries Ltd
Trial: Phase III
Indication: Relapsing–remitting multiple sclerosis
Teva Pharmaceutical Industries Ltd recently announced the results of their Phase III trial investigating the efficacy, safety and tolerability of glatiramer acetate (GA) 40 mg compared with the approved 20-mg dose (Copaxone®) for the treatment of relapsing–remitting multiple sclerosis (RRMS).
A total of 1155 patients with RRMS participated in the randomized, double-blind trial. The primary clinical outcome was the rate of confirmed relapses.
Although the 40-mg dose of GA was not found to be more effective than Copaxone, it did maintain the favorable safety and tolerability profile of Copaxone.
“While the trial did not demonstrate an enhanced efficacy at the higher dose level, the study reaffirms that Copaxone 20 mg, the leading multiple sclerosis therapy, remains the optimal treatment dose with unmatched long-term efficacy confirmed over 10 years,” commented Moshe Manor, Group Vice President , Global Innovative Resources. “Teva is committed to ongoing research in the field of multiple sclerosis and will continue to move forward towards providing additional treatment options to multiple sclerosis patients.”
Source: Teva Pharmaceutical Industries Ltd Press Release: Teva provides update on forte trial. www.tevapharm.com/pr/2008/pr_770.asp
Alzheimer’s disease treatment hope from UK and Canadian researchers
Published in an early online issue of Nature Chemical Biology, researchers from the University of York (York, UK) and Simon Fraser University (BC, Canada) have designed an enzyme inhibitor that may lead to the development of novel drugs to treat Alzheimer’s disease (AD).
Hyperphosphorylation of the protein tau is characteristic of AD. By tricking the brain into adding sugars onto the tau proteins rather than phosphates, the enzyme thiazoline is able to prevent the phosphorylation of tau in animal models in vivo.
Gideon Davies, the coauthor of the published study explained, “We hope that the work will evolve into new drugs to treat AD, although that is still many years off. The work highlights the synergy of studying the chemistry of enzymes in living cells.”
Source: Yuzwa SA, Macauley MS, Heinonen JE et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.Nat. Chem. Biol. (2008) (Epub ahead of print).
Titan Pharmaceuticals Inc. report results of Phase IIb trial of Spheramine®
Drug: Spheramine®
Maufacturer: Titan Pharmaceuticals Inc.
Trial: Phase IIb
Indication: Advanced Parkinson’s disease
Titan Pharmaceuticals Inc., recently announced the failure of the Phase IIb study of the cell-based treatment Spheramine® for the treatment of advanced Parkinson’s disease (PD). Spheramine treatment involves injecting retinal pigment epithelial cells into the CNS in order to produce dopamine.
The multicenter, double blind, randomized, sham surgery-controlled STEPS trial involving 71 patients with advanced PD was designed to test the safety, tolerability and efficacy of Spheramine compared with sham surgery. Unfortunately, no significant differences were found between sham surgery and Spheramine treatment at 12 months follow-up.
Marc Rubin, President and CEO of Titan commented, “We are disappointed by these data as we have been diligently working to address the critical unmet medical need facing Parkinson’s patients.”
Source: Press Release: Titan Pharmaceuticals announces Spheramine® initial Phase IIb results. http://phx.corporate-ir.net/phoenix.zhtml?c=95579&p=irol-newsArticle&ID=1171417