Day: 08/15/2013

Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives.

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Glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by substantial adverse outcomes such as osteoporosis, diabetes, and obesity. These unwanted outcomes are a major dilemma for clinicians because improvements in the primary disorder seem to be achievable only by accepting substantial adverse effects that are often difficult to prevent or treat. To understand the pathogenesis of glucocorticoid-induced osteoporosis, it is necessary to consider that the actions of glucocorticoids on bone and mineral metabolism are strongly dose and time dependent. At physiological concentrations, endogenous glucocorticoids are key regulators of mesenchymal cell differentiation and bone development, with additional regulatory roles in renal and intestinal calcium handling. However, at supraphysiological concentrations, glucocorticoids affect the same systems in different and often unfavourable ways. For many years, these anabolic and catabolic actions of glucocorticoids on bone were deemed paradoxical. In this Review, we highlight recent advances in our understanding of the mechanisms underlying the physiology and pathophysiology of glucocorticoid action on the skeleton and discuss present and future management strategies for glucocorticoid-induced osteoporosis.

Source: Lancet

 

 

 

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.

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Background

Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer.

Methods

In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18—75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506.

Findings

400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67—1·05; median progression-free survival 4·6 months [95% CI 3·5—6·3] vs 3·4 months [2·3—3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033).

Interpretation

Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.

Source: Lancet

 

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

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Background

Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.

Methods

This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.

Findings

The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03—1·45] per 10 μg/m3). For PM2·5 the HR was 1·18 (0·96—1·46) per 5 μg/m3. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10—2·08) and 1·55 (1·05—2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99—1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95—1·07] per 20 μg/m3) or traffic intensity on the nearest street (HR 1·00 [0·97—1·04] per 5000 vehicles per day).

Interpretation

Particulate matter air pollution contributes to lung cancer incidence in Europe.

Source: Lancet

 

Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study.

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Summary

Background

A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock.

Methods

We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus.

Findings

50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies.

Interpretation

MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection.

Source: Lancet

 

 

Neurological complications of dengue virus infection.

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Dengue is the second most common mosquito-borne disease affecting human beings. In 2009, WHO endorsed new guidelines that, for the first time, consider neurological manifestations in the clinical case classification for severe dengue. Dengue can manifest with a wide range of neurological features, which have been noted—depending on the clinical setting—in 0·5—21% of patients with dengue admitted to hospital. Furthermore, dengue was identified in 4—47% of admissions with encephalitis-like illness in endemic areas. Neurological complications can be categorised into dengue encephalopathy (eg, caused by hepatic failure or metabolic disorders), encephalitis (caused by direct virus invasion), neuromuscular complications (eg, Guillain-Barré syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these categories is possible. In endemic countries and after travel to these regions, dengue should be considered in patients presenting with fever and acute neurological manifestations.

Diagnosis

Clinical suspicion is essential for diagnosis of dengue because many symptoms are non-specific. Various methods are available for laboratory confirmation. During the first days of infection, dengue virus is present in blood; thus, at that time, detection of NS1 antigen or RNA by RT-PCR and viral culture are appropriate diagnostic methods.1 Dengue virus-specific IgM antibodies are present in serum samples 3—10 days after disease onset.1 IgM capture (MAC)-ELISA is the most widely used serological test. Antibodies against other flaviviruses (eg, Japanese encephalitis, West Nile virus, yellow fever) might cross-react with dengue virus, leading to false-positive reactions.136

In endemic countries, or among travellers who recently (<14 days) returned from such regions, dengue should be ruled out in patients with fever and neurological features (panel 2). If possible, lumbar puncture should be done and CSF analysed for abnormalities and for dengue virus-specific antibodies, NS1 antigen, or dengue virus RNA, depending on available laboratory facilities. Differential diagnosis in patients with febrile encephalopathy includes malaria, tuberculosis, leptospirosis, rickettsial infection, and other bacterial or viral diseases (caused by, for example, Japanese encephalitis, West Nile virus, or herpes simplex virus [HSV]), depending on the local epidemiology. In a prospective hospital-based study in Vietnam, most children with acute encephalitis of presumed viral origin were infected with Japanese encephalitis (26%), followed by enteroviruses (9%) and dengue virus (5%).30 In adults and adolescents in Brazil, dengue was the leading cause of viral encephalitis (47%), followed by infections with HSV-1.31

To differentiate dengue encephalitis from encephalopathy, detection of dengue virus, NS1 antigen, or dengue virus-specific IgM antibodies in CSF is helpful. Nevertheless, sensitivity of serological techniques can be low. Dengue virus-specific IgM antibodies have been recorded in CSF of 22—33% of patients diagnosed with dengue encephalitis (Table 1, Table 2).90Detection of dengue virus in CSF could be hampered by low sensitivity of RT-PCR in CSF, compared with findings in serum, because of a lower viral load.137 Moreover, measurement of IgM antibodies in CSF might not be a reliable diagnostic marker of dengue CNS involvement, owing to low titres in CSF.138 Abnormalities in CSF—such as lymphocytic pleocytosis—support the diagnosis of dengue encephalitis, but they are not always present (Table 1, Table 2, Table 3). A mild increase in CSF protein has been recorded.28 In a series of patients with neurological complications of dengue, four of seven with encephalitis had no alterations in CSF.90 Therefore, normal CSF cellularity should not exclude dengue encephalitis.

The case definitions in panel 2 are designed to be used epidemiologically and clinically and to guide diagnosis and prognosis. Although we propose criteria for a classification scheme, a topic as challenging and as controversial as dengue encephalitis needs to be addressed in a standard way. Prospective studies are needed to assess the specificity and sensitivity of the proposed case definitions and to generate supporting evidence. Cases fulfilling neither the definition for encephalitis nor that for encephalopathy—eg, without CSF testing or when categories are overlapping—can be categorised as other or non-specified dengue CNS involvement.

Neuroimaging might provide additional clues in the diagnosis of neurological complications of dengue. In dengue encephalitis, brain MRI can be normal or show focal parenchymal abnormalities.22, 41 Nevertheless, no specific MRI findings suggestive of dengue encephalitis have been reported. Neuroimaging features of patients with dengue are diverse, with cerebral oedema the most commonly reported finding.77 Meningeal enhancement on post-contrast MRI has been reported occasionally as well.77

Finally, EEG abnormalities can be seen in dengue patients with neurological complications. In a study of 23 patients with dengue virus infection and neurological symptoms, EEG abnormalities were recorded in 12 people.139 Slowing on EEG can be seen, but this finding is unspecific and could be attributable to seizures, intracranial haemorrhage, and viral infection per se, besides encephalopathy.77

Management

Currently, no effective antiviral agents are available to treat symptomatic dengue virus infection.140 Therefore, management remains supportive. In mild cases, antipyretic drugs and oral fluids could be useful. Acetyl-salicylic derivatives and other non-steroidal anti-inflammatory drugs should be avoided. Management of haemorrhagic complications should be initially conservative. Precise management of intravenous fluids is needed, and blood or platelet transfusion is only necessary when severe bleeding takes place.1

In patients with severe dengue and signs of plasma leakage, prompt fluid resuscitation is imperative, with close monitoring of packed-cell volume to avoid fluid overload. Isotonic crystalloid solutions should be used, with isotonic colloid solutions reserved for patients presenting with profound shock or those who do not have a response to initial crystalloid treatment.140, 141 In a randomised controlled trial from Vietnam,142 use of oral prednisolone during the early acute phase of dengue infection was not associated with a reduction in the development of shock or other recognised complications of dengue virus infection.

For supportive management of patients with neurological manifestations, possible underlying causes such as intracranial bleeding, liver failure, hyponatraemia, hypokalaemia, or metabolic acidosis should be ruled out and—if possible—corrected. Management of dengue encephalitis remains supportive and should include adequate hydration, nutrition, monitoring of consciousness, and maintenance of airways.143 Symptomatic seizures should be treated with non-hepatotoxic anticonvulsants. Decompressive craniotomy and cerebral haematoma evacuation were done in two patients with dengue after correction of prothrombin time and platelet count.92 Nevertheless, prognosis is not good and, in one case series, two of five patients died.92 At this moment, haematoma surgery cannot be proposed as a routine treatment for dengue virus intracranial bleeding.

Some clinicians recommend treatment of immune-mediated dengue CNS involvement with pulses of intravenous methylprednisolone for several days.50, 69, 72 However, up to now, no randomised controlled trial has been undertaken to show the efficacy of this approach in patients with dengue myelitis or acute disseminated encephalomyelitis. High doses of intravenous immunoglobulin might be useful to treat post-dengue Guillain-Barré syndrome. Supportive treatment—including hydration and analgesic drugs—is used for myalgia and transitory muscle dysfunction. The effectiveness of corticosteroids in dengue myositis remains to be proven.

No treatment has been approved for neuro-ophthalmic manifestations of dengue. Steroids have been administered previously because of possible underlying immune mechanisms, although up to now no randomised trials have been done. Topical steroids have been used to treat anterior uveitis, whereas pulsed intravenous methylprednisolone or systemic oral steroids might be indicated for extensive retinal vasculitis.120

Currently, no vaccine is available for protection against dengue. However, several vaccine candidates are in development.

Conclusions and future research

Dengue should be included in the differential diagnosis of acute febrile disease with neurological manifestations in dengue-endemic countries and in patients with a recent travel history to an endemic region. Many neurological manifestations of dengue have been recorded, ranging—with substantial overlap—from encephalitis and encephalopathy to immune-mediated syndromes and muscle involvement. Recent evidence suggests that dengue virus has neuroinvasive capacity. In several studies in endemic areas, a large proportion of viral encephalitis was caused by dengue virus.26—32 However, even though CNS involvement is included now as a criterion for severe dengue in the 2009 WHO case classification,1 no standardised case definitions or diagnostic criteria for dengue encephalitis or encephalopathy have been agreed, which leads to inconsistent use of these terms in published work.

An updated WHO dengue guideline should include a case definition for dengue encephalitis and encephalopathy, to guide clinicians and clinical epidemiological researchers into this topic. A case classification—such as the one proposed in panel 2—could serve as a starting point, which could be reviewed by WHO, agreed by consensus and best available current evidence, and refined as additional data become available from prospective studies. For this reason, assessment of CSF in patients with suspected neurological manifestations of dengue should be standardised. Very few published reports present findings of CSF testing for dengue virus, dengue virus-specific IgM antibodies, or NS1 antigen combined with CSF cellularity and confirmation of dengue in serum samples in a consistent way. Further epidemiological and neuropathological studies are needed to ascertain the true incidence and burden of neurological complications of dengue, to elucidate the underlying pathophysiology, and to assess the sensitivity and specificity of diagnostic markers for dengue encephalitis.

Source: Lancet

Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.

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Summary

Background

Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO.

Methods

In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556.

Findings

31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71—4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06—9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses.

Interpretation

Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done.

Source: Lancet

Chernobyl’s legacy recorded in trees.

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Exposure to radiation from the 1986 Chernobyl accident had a lasting negative legacy on the area’s trees, a study has suggested.

Researchers said the worst effects were recorded in the “first few years” but surviving trees were left vulnerable to environmental stress, such as drought.

 

They added that young trees appeared to be particularly affected.

Writing in the journal Trees, the team said it was the first study to look at the impact at a landscape scale.

“Our field results were consistent with previous findings that were based on much smaller sample sizes,” explained co-author Tim Mousseau from the University of South Carolina, US.

“They are also consistent with the many reports of genetic impacts to these trees,” he told BBC News.

“Many of the trees show highly abnormal growth forms reflecting the effects of mutations and cell death resulting from radiation exposure.”

Prof Mousseau, who has been carrying out field studies since 1999 within the 30km (19-mile) exclusion zone around the site of the 1986 explosion, said it was the first time that a study of this scale – involving more than 100 Scots pines (Pinus sylvestris) at 12 sites – had been conducted.

“There was one similar study conducted before but it only looked at a total of nine trees and was mainly interested in wood structure, not growth,” he said.

“Another study was performed in the 1950s but it was for a different tree in the US and it used a single external gamma source suspended above the ground to show growth effects for a very limited number of trees.”

For this study, the team took core samples from Scots pine trees for a number of reasons, such as the species is found across Europe and well dispersed within the Chernobyl region.

“They are also a favourite for silviculture and have enormous economic value,” Prof Mousseau added.

“Also, based on past work and our own observations, they appeared to be a good target for radioecology as they showed signs of being impacted by the fallout.

“In fact, one of the first ecological observations at Chernobyl was the death of the so-called red forest: a stand of these pines which very quickly died and turned red following the disaster.”

Scots pines’ tree rings were also easier to read than other species, such as birch, found in the study area, he explained.

Prof Mousseau and his team hope to follow up this study by carrying out similar work in the Fukushima region in Japan, where logging also had considerable economic importance and pine trees were widely dispersed.

“Based on our limited field observations in the most contaminated regions of Fukushima prefecture, there did not appear to be a major die off as seen in Chernobyl for Scots pines,” he said.

“However, anecdotally, we have noticed significant die off of growing tips and branches in some areas that suggests that there could be impacts on growth.

“This is worth further investigation.”

Source: BBC

 

 

 

 

Mers coronavirus: Dromedary camels could be source.

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Dromedary camels could be responsible for passing to humans the deadly Mers coronavirus that emerged last year, research suggests.

Tests have shown the Mers (Middle East Respiratory Syndrome) virus, or one that is very closely related, has been circulating in the animals, offering a potential route for the spread.

The study is published in the journal Lancet Infectious Diseases.

But the scientists say more research is needed to confirm the findings.

The Mers coronavirus first emerged in the Middle East last year. So far, there have been 94 confirmed cases and 46 deaths.

While there has been evidence of the virus spreading between humans, most case are thought to have been caused by contact with an animal. But until now, scientists have struggled to work out which one.

‘Smoking gun’

To investigate, an international team looked at blood samples taken from livestock animals, including camels, sheep, goats and cows, from a number of different countries.

They tested them for antibodies – the proteins produced to fight infections – which can remain in the blood long after a virus has gone.

Continue reading the main story

“Start Quote

The definitive proof would be to isolate the virus from an infected animal ”

Professor Paul KellamWellcome Trust Sanger Institute

Professor Marion Koopmans, from the National Institute of Public Health and the Environment and Erasmus University in The Netherlands, said: “We did find antibodies that we think are specific for the Mers coronavirus or a virus that looks very similar to the Mers coronavirus in dromedary camels.”

The team found low levels of antibodies in 15 out of 105 camels from the Canary Islands and high levels in each of the 50 camels tested in Oman, suggesting the virus was circulating more recently.

“Antibodies point to exposure at some time in the life of those animals,” Prof Koopmans explained.

No human cases of the Mers virus have been reported in Oman or the Canary Islands, and the researchers say they now need to test more widely to see if the infection is present elsewhere.

This would include taking samples from camels in Saudi Arabia, the country where the virus is the most prevalent.

‘Priority search’

Prof Koopmans said: “It is a smoking gun, but it is not definitive proof.”

Commenting on the research, Professor Paul Kellam from the Wellcome Trust Sanger Institute in Cambridge and University College London, said the research was helping to narrow down the hunt for the source of the virus.

But he told BBC News: “The definitive proof would be to isolate the virus from an infected animal or to be able to sequence and characterise the genome from an infected animal.”

Health officials say confirming where the virus comes from is important, but then understanding how humans get infected is a priority.

Gregory Hartl, from the World Health Organization, said: “Only if we know what actions and interactions by humans lead to infection, can we work to prevent these infections.”

Data suggests that it is not yet infectious enough to pose a global threat and is still at a stage were its spread could be halted.

Source: BBC

Drug licensed for advanced rare skin cancer.

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Cancer experts have welcomed a move that makes a drug for patients with advanced skin cancer available in the UK.
Regulators have licensed Erivedge (vismodegib) for people with severe basal skin carcinoma.
Currently, treatment is limited to surgery or radiotherapy.
Cancer Research UK, whose scientists discovered the mechanisms the drug uses, said the decision was “great news for patients”.
Basal cell carcinoma is the most common form of skin cancer in the UK and is often found on the head and neck.
Around 700 people a year in the UK are diagnosed with an advanced form of the cancer – a small number, but cancer experts say the lack of treatment options currently available is what makes this change significant.
Many will have already had surgery and radiotherapy, and it is often considered inappropriate for them to have further procedures
Continue reading the main story
“Start Quote
“This drug is a major advance for the treatment of this disease” ”
Dr Harpal KumarCancer Reseach UK
Erivedge, made by Roche, had to be licensed by the European Medicines Agency before it could be made available in the UK.
The drug, which patients take once a day, costs around £6,000 per month.
Clinicians who want to give it to their patients will have to apply to the Cancer Drugs Fund in England.
In Scotland, Wales and Northern Ireland, doctors would have to ask their local health provider to fund the drug.
Hedgehog pathway
The drug works by blocking a process in the body that has gone awry.
The hedgehog pathway is a chemical process that is normally only active in the early stages of life and which becomes less so in adulthood.
The reactivation of this process is responsible for cell growth in more than 90% of basal cell carcinoma cases.
Dr Harpal Kumar, chief executive of Cancer Research UK, said: “We are proud to have played a key role in the early development of this drug and we’re delighted that it has passed this regulatory hurdle and is approved for use in the UK.
“This drug is a major advance for the treatment of this disease, providing advanced basal cell carcinoma patients with a new treatment option.
“This is great news for patients.”
Source: Cancer experts have welcomed a move that makes a drug for patients with advanced skin cancer available in the UK.
Regulators have licensed Erivedge (vismodegib) for people with severe basal skin carcinoma.
Currently, treatment is limited to surgery or radiotherapy.
Cancer Research UK, whose scientists discovered the mechanisms the drug uses, said the decision was “great news for patients”.
Basal cell carcinoma is the most common form of skin cancer in the UK and is often found on the head and neck.
Around 700 people a year in the UK are diagnosed with an advanced form of the cancer – a small number, but cancer experts say the lack of treatment options currently available is what makes this change significant.
Many will have already had surgery and radiotherapy, and it is often considered inappropriate for them to have further procedures
Continue reading the main story
“Start Quote
“This drug is a major advance for the treatment of this disease” ”
Dr Harpal KumarCancer Reseach UK
Erivedge, made by Roche, had to be licensed by the European Medicines Agency before it could be made available in the UK.
The drug, which patients take once a day, costs around £6,000 per month.
Clinicians who want to give it to their patients will have to apply to the Cancer Drugs Fund in England.
In Scotland, Wales and Northern Ireland, doctors would have to ask their local health provider to fund the drug.
Hedgehog pathway
The drug works by blocking a process in the body that has gone awry.
The hedgehog pathway is a chemical process that is normally only active in the early stages of life and which becomes less so in adulthood.
The reactivation of this process is responsible for cell growth in more than 90% of basal cell carcinoma cases.
Dr Harpal Kumar, chief executive of Cancer Research UK, said: “We are proud to have played a key role in the early development of this drug and we’re delighted that it has passed this regulatory hurdle and is approved for use in the UK.
“This drug is a major advance for the treatment of this disease, providing advanced basal cell carcinoma patients with a new treatment option.
“This is great news for patients.”
Source: BBC

 

Test of famous faces ‘helps to spot early dementia.

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Asking patients to identify pictures of famous people, such as Elvis Presley and Diana, Princess of Wales, may help spot early dementia, say researchers.

Doctors currently use simple mental agility tests to screen for the disease, but US experts believe a face recognition test should be used too.

A small study in the journal Neurology found it could flag up the beginnings of one type of dementia in 30 patients.

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Trials are needed to see if it works for other forms of the disease.

The research at Northwestern University in Chicago found that people with early onset primary progressive aphasia (PPA), a rare form of dementia, struggled to identify black and white prints of 20 famous people, including John F Kennedy, Albert Einstein and Martin Luther King.

Participants were given points for each face they could name. If they could not name the face, they were asked to identify the famous person through description instead.

‘Lot of nuances’

Compared with 27 dementia-free volunteers, the 30 participants with PPA scored poorly on the famous face test.

While it is normal for anybody to forget a name or a face from time to time, failing to recognise someone as famous as Presley suggests there could be a deeper-rooted cause.

Brain scans of the participants with PPA revealed loss of brain tissue in areas that deal with recognising faces.

Tamar Gefen, lead author of the study, said it would be useful to add the test to the others that doctors use to spot early dementia.

… as would correctly identifying Albert Einstein

She said: “It could be incorporated into a battery of tests for dementia. There are a lot of nuances and differences in dementia so it is good to use different tests.”

Doctors already screen by asking questions such as “What month and season is it?”

_69242963_elvispa

The celebrity test would need to be adapted for the individual. Someone aged 45 might not be expected to recognise film stars from the 1930s, and a patient in their eighties might not be familiar with current pop stars, for example.

Dr Marie Janson, of Alzheimer’s Research UK, said: “It’s important to be able to give an accurate diagnosis for people with dementia so they can gain access to the right care and treatments, but the different forms of dementia can be difficult to identify.

“Studies such as this could increase our understanding of the way the brain is affected by different forms of dementia, but we must invest in research if results like these are to be used to move towards better diagnosis.”

A spokeswoman for the Alzheimer’s Society said: “Tests like this could help identify rarer forms of dementia which might otherwise be overlooked.

“However, problems with facial recognition are not a symptom of all types of dementia, so more research is needed to see whether adaptations of this approach could have wider use.”

Source: BBC