December 26, 2011

First Data to Show Antihypertensive Therapy Prolongs Life

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December 20, 2011 (New Brunswick, New Jersey) — The first long-term data from a high-blood-pressure study, the Systolic Hypertension in the Elderly Program (SHEP), show that each month of chlorthalidone-based therapy was associated with approximately one day of extension in life, free from cardiovascular death [1].

"The main findings are that after 22 years of follow-up, when about 60% of the participants in SHEP were dead, we saw a prolonged life expectancy in those who took the active treatment for 4.5 years, and that is the first time this has been reported in studies of hypertension, because you have to wait a long time to find out differences in life expectancy," lead author Dr John B Kostis (UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ) told heartwire. "In hypertension trials, by the time everybody dies, the investigators have died," he added.

The study "is a strong message that may result in increased patient adherence to drug therapy and decrease the degree of therapeutic inertia by healthcare providers," he and his colleagues say in their paper in the December 21, 2011 issue of the Journal of the American Medical Association.
Kostis cautions, however, that the gains relate primarily to CVD avoidance and that "everyone has to die from something," but he points out that other benefits of antihypertensive treatment, such as preventing strokes, could arguably be even more important than prolonging life.

SHEP Participants Were 72, on Average, When They Entered the Trial

The SHEP trial was conducted between March 1985 and January 1988, and just over 4700 patients aged, on average, 72 years were randomized to active treatment with chlorthalidone--with atenolol added if antihypertensive control was not sufficient--or placebo for 4.5 years. After this time, all patients were asked to go on active therapy.

At 22 years later, life-expectancy gain--expressed as the area between the active and placebo survival curves--was 105 days for all-cause mortality and 158 days for cardiovascular death.

The active-treatment group had higher survival free from cardiovascular death vs the placebo group (hazard ratio 0.89; p=0.03), but similar survival for all-cause mortality (HR 0.97; p=0.42).

There were 1416 deaths (59.9%) in the active-treatment group and 1435 in the placebo group (60.5%). But cardiovascular death was lower in the active-treatment group--669 deaths (28.3%) vs 735 deaths (31.0%) in the placebo group (p=0.03).

Time to 70th-percentile survival was 0.56 years longer in the active-treatment vs the placebo group for all-cause mortality and 1.41 years for survival free from CV death.

Stroke Prevention One of Key Messages

Kostis stresses, therefore, that the gains in life expectancy relate mainly to CVD. "If you do not die from CVD then you have more chance to die from other conditions. We found the CVD benefit was much higher than the overall benefit, because non-CV causes [of death] were more common in people treated [with antihypertensive therapy] at the beginning of SHEP.

"We all die, and if you don't die from heart disease you have the opportunity of dying from something else. Immortality hasn't been achieved yet in humans," he noted.
But, he believes, "it's better to live an extra year, then die from cancer." And he points out that other benefits of antihypertensive therapy, such as preventing strokes, are perhaps even more important. "Preventing one stroke has many implications other than life expectancy; stroke is a terrible thing."

Another key message from this trial is that the earlier therapy is started the better, says Kostis. "These patients happened to be elderly; they were 72, on average, when they were enrolled in this trial. But if you start treatment earlier you would have even better benefit. If you start therapy early and live 20 more years, you will be productive and enjoy life."

Kostis reported receiving grant support and travel to meetings from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Aging (NIA). Disclosures for the coauthors are listed in the paper.

  1. Kostis, JB, Cabrera J, Cheng JQ et al. Association between chlorthalidone treatment of systolic hypertension and long-term survival. JAMA 2011; 306:2588-2593.

December 16, 2011

A Third of All Cancers in the UK Can Be Prevented, Review Discovers

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A third (more than 100 000 cases) of all cancers in the United Kingdom are caused by just four risk factors and are potentially preventable, concludes a comprehensive review of the evidence.

December 13, 2011

Childhood obesity can be prevented - Cochrane

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Cochrane logo

By BMJ 2011;343:d8014

Strategies to promote healthy eating and physical activity in schools and other settings are effective in preventing childhood obesity, says an updated Cochrane Collaboration review released last week.

The publication is an update of a 2001 review that reached more equivocal conclusions when last updated in 2005. It includes 55 studies of interventions targeting children up to age 18 years, with most involving children aged 6 to 12 years.

The review’s lead author, Professor Elizabeth Waters, the Jack Brockhoff chair of child public health at the University of Melbourne, told the BMJ that the most effective interventions sought to change social and physical environments and norms, rather than just individual behaviour.

These included policies for healthy eating and physical activity in schools and early childcare settings, support for teachers and other staff to do health promotion, and support from parents and at home for children to eat better, move more, and spend less time looking at screens.

The review found that the best estimate of effect on body mass index (BMI) (kg/m2) was a reduction of 0.15, or a 0.4-1.6% reduction in individual weight, which would correspond to a “small but clinically important shift in population BMI if sustained over several years.”

Professor Waters said: “The implication of this is quite remarkable—were these programmes able to be implemented across the population, we can be confident that this would translate into a reduction in body weight that would have substantial effects on the consequent child health concerns, such as the rising rates of diabetes.”

She said that policy makers with responsibility for schools and other settings where children spent time had a responsibility to act.

“By not putting in place these strategies, which we know work, the health of children will be affected as obesity rates are predicted to continue to rise,” she said.

The review’s authors said there was now so much evidence about the impact of interventions in children aged 6 to 12 that further such trials in this age group seemed unnecessary.

“Childhood obesity prevention research must now move towards identifying how effective intervention components can be embedded within health, education and care systems and achieve long term sustainable impacts,” they wrote.

However, the review found “substantial unexplained heterogeneity” in the size of intervention effects, and the authors suggested this could reflect “small study bias.”

Professor Boyd Swinburn, director of the World Health Organization’s Collaborating Centre for Obesity Prevention at Deakin University in Melbourne, said policy makers must now respond to the challenge of rolling out the interventions widely. But he cautioned that the review findings did not absolve governments from taking broader action at a population level to tackle junk food marketing and to ensure better regulation of food labelling.

Jane Martin, senior policy adviser for the Obesity Policy Coalition, an organisation that campaigns for change in policy and regulation to help prevent obesity, said the findings reinforced the importance of such broader policy actions to ensure maximum return from investment in school and community interventions. The strategies identified by the review could be even more effective if not counteracted by the influence of junk food marketing, she said.

“A comprehensive approach at all levels of government and society are so important,” said Ms Martin, adding: “You can control the availability in schools, but governments should be looking at controlling the placement of fast food outlets close to schools and the marketing of unhealthy foods overall.”

The review also identified several gaps in evidence, and the authors called for more studies to develop, implement, and evaluate prevention interventions in young children and adolescents.

They also want better reporting of the impact of interventions on health inequalities and of potential harms of interventions. The review noted that none of the eight studies targeting adolescents explicitly reported unintended outcomes or measures of harm, despite body image sensitivities in this age group.

December 12, 2011

Memories of Christmases Past in Hospital

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Earlier this year, 2011, I came across a wonderful piece written by George Watts, a retired consultant surgeon in Birmingham. He had written the piece way back in 2006, and published it first on BMJ. Although "old", the freshness of the message resonated strongly into me and gave me such pleasure that I decided to share it here with you. I do hope you enjoy it like I did.

December 11, 2011

Gene therapy achieves early effective success against hereditary bleeding disorder

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Sebastian trial patient
Trial participant Sebastian Misztal (Credit: UCLH/UCL NIHR Biomedical Research Centre)
Study of gene therapy developed at UCL and St. Jude Children’s Research Hospital offers first proof adults with haemophilia B benefit from treatment, reducing need for injections with clotting factor to prevent bleeds.

Symptoms improved significantly in adults with the bleeding disorder haemophilia B following a single treatment with gene therapy developed by researchers at St. Jude Children’s Research Hospital in Memphis, US and demonstrated to be safe in a clinical trial conducted by UCL.

The findings of the six-person study mark the first proof that gene therapy can reduce disabling, painful bleeding episodes in patients with the inherited blood disorder. Results of the Phase I study appeared online ahead of print yesterday in the New England Journal of Medicine. The research is also scheduled to be presented today 11th December at the 53rd annual meeting of the American Society of Hematology in San Diego, US.

Four study participants stopped receiving protein injections to prevent bleeding episodes after undergoing the therapy and have not suffered spontaneous bleeding. Several have also participated in marathons and other activities that would have been difficult prior to gene therapy. The study participants were all treated at the Royal Free Hospital in London under the care of Professor Edward Tuddenham, a pioneer in the field of blood coagulation and a study co-author.

“This is a potentially life-changing treatment for patients with this disease and an important milestone for the field of gene therapy. It could have ramifications for the treatment of haemophilia A, other protein and liver disorders and chronic diseases such as cystic fibrosis,” said first author Dr Amit Nathwani, UCL Cancer Institute, Royal Free Hospital, University College Hospital (UCH) and NHS Blood and Transplant (NHSBT).

Haemophilia B is caused by an inherited mistake in the gene for making a protein called Factor IX, which is essential for normal blood clotting. The gene is carried on the X chromosome. As a result, haemophilia B is almost exclusively a disease of men. About 1 in 30,000 individuals inherit the mutation.

Previous efforts to ease haemophilia B symptoms by introducing a correct copy of the gene have been unsuccessful.

The current study used adeno-associated virus (AAV) 8 to deliver the Factor IX gene along with additional genetic material into the patient’s liver. AAV8 was picked because the incidence of natural infection with AAV8 is low. It belongs to a family of viruses that target liver cells, but do not cause disease in humans or integrate into human DNA. Participants in this study received no immune suppressing drugs prior to gene therapy. This approach was jointly pioneered by St. Jude and UCL, initially in the laboratory of study co-author Professor Arthur Nienhuis a member of the St. Jude Department of Hematology.

For this study, each patient received a one-time infusion of the vector into a vein in the arm. Two patients each were treated with escalating doses of the vector. Following treatment, Factor IX levels rose in all six patients from less than 1% of normal levels prior to the gene therapy to between 2 and 12%.

Factor IX levels increased the most in the two study volunteers who received the highest dose of the experimental vector, researchers said. After treatment, levels of the protein ranged from 3 to 12% in those men. Even modest increases that raise Factor IX production to more than 1% of normal levels has the potential to dramatically affect a patient’s quality of life and reduce bleeding episodes, said the study’s senior author Dr Andrew Davidoff, chair of the St. Jude Department of Surgery.

“The first patient has been followed for the longest time, and his levels have remained at 2% for more than 18 months. These results are highly encouraging and support continued research. More patients are scheduled to be enrolled in future trials scheduled to begin later this year,” Davidoff said.

One of the participants who received the highest dose of the vector underwent successful, short-term steroid treatment after his liver enzymes rose slightly after the vector infusion. The rise signalled mild liver damage. The volunteer remained otherwise healthy, his Factor IX levels remain above pre-infusion levels and his liver enzymes have returned to normal. Liver enzymes also rose slightly, but remained in the normal range, for the other participant who received the highest dose of the vector. The participant also received a short course of steroids.

Researchers believe an immune response targeting the vector triggered the elevated enzyme levels. A similar response was reported in earlier gene therapy trials conducted by other investigators using a different vector.

The vector used in this study was produced at the Good Manufacturing Practices (GMP) facility on the St. Jude campus. The GMP operates under government-approved manufacturing guidelines and produces highly specialized medicines, vaccines and other products that pharmaceutical companies are reluctant to pursue. The vector can also now be produced in a similar facility at UCL.

The research was funded in part by The Katharine Dormandy Trust, Medical Research Council, Wellcome Trust, NHS Blood and Transplant and the UCLH/UCL National Institute for Health Research Biomedical Research Centre, all in the UK. In the US, the research was funded by the National Institutes of Health, the Assisi Foundation of Memphis and ALSAC. (Credit: UCL News)

GMC strikes off Gynaecologist for botching vaginal surgery and dishonesty

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A gynaecologist who botched four vaginal laser operations and an abortion and forged a professional indemnity certificate has been struck off by the General Medical Council.

Phanuel Dartey, who specialised in vaginal laser cosmetic surgery, significantly over-reduced the patients’ labia minora in two cases. One woman was left in continuing pain, and the other had visible scarring and asymmetry and had to undergo revision surgery (BMJ 2011;343:d7442, 16 Nov, doi:10.1136/bmj.d7442).

In two other cases he performed “inappropriate” laser surgery for urinary incontinence, leaving one woman with worse incontinence than before.

Dr Dartey, who originally came from Ghana and qualified in the former Soviet Union, had practising privileges at the private Queen Anne Street Medical Centre near London’s Harley Street and at the Marie Stopes International Clinic in South Ealing, west London.

Robin Knill-Jones, who chaired the GMC’s fitness to practise panel, said, “In the panel’s judgment there is a continuing risk to patients from the way Dr Dartey conducts his practice. His dishonest actions in relation to professional indemnity were a serious abuse of the trust that his patients and those with whom he worked were entitled to place in him.

“The panel considers that the extent and seriousness of Dr Dartey’s clinical misconduct, the gravity of his dishonesty, and his subsequent lack of insight evidence a harmful attitudinal problem.”

When Dr Dartey carried out the termination in 2006 on a woman who had travelled from Ireland, he perforated her uterus and failed to remove the fetal thorax. When she returned home she became extremely ill and was in hospital for two months, the panel heard.

Dr Dartey’s membership of the Medical Protection Society had lapsed in 2002, and he had no indemnity cover when he performed the abortion. The panel found that a membership certificate he sent to Marie Stopes International purporting to cover 2005-6 was a forgery.

Dr Knill-Jones said, “Each of the five patients with which this inquiry has been concerned has suffered from the events in question. In his written communications to the GMC Dr Dartey has shown little remorse or acknowledgment of, or insight into, his failures.

“He has rather adopted a derogatory attitude towards his patients, accusing one of racism, another of blackmail, a third of causing her own problems by failing to follow his advice, and another of reporting him to the GMC because she wanted free corrective surgery for an unrelated problem. The panel has found no substance in any of these complaints and regards Dr Dartey’s lack of insight as a matter of serious concern.” BMJ 2011;343:d7947