Clinical Review: Treatment of Helicobacter pylori infection

Clinical Review, by: L Fuccio, research fellow et al, Department of Internal Medicine and Gastroenterology, University of Bologna.
BMJ, 15 September 2008

• The prevalence of H pylori varies widely and is about 50% in international population studies. Helicobacter pylori is one of the most common human infections, and about half of the world’s population carries this organism. Since its discovery in 1984, H pylori has been recognised as a major cause of several upper gastrointestinal diseases.
• Triple and quadruple multidrug regimens are standard treatment
• Resistance to clarithromycin and metronidazole and lack of adherence to treatment are the main predictors of treatment failure
• The choice of the most effective regimen should be based on the prevalence of antibiotic resistance, especially resistance to clarithromycin and metronidazole
• Individualised treatment based on antimicrobial susceptibility has a limited role in H pylori eradication strategies
• The overall risk of reinfection is estimated at 3.4% per patient year in developed countries, rising to 8.7% in developing countries

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Management of postnatal depression, a clinical review

By: Charles Musters, specialist registrar in perinatal psychiatry, Elizabeth McDonald, consultant in perinatal psychiatry and Ian Jones, senior lecturer in perinatal psychiatry.
BMJ, 8 August 2008

• Postnatal depression occurs after 13% of births.
• The nature of the puerperal trigger is still unknown, but several psychological, social, and biological factors probably play a part. Genetic factors have been implicated
• A previous history of postnatal depression or of any mental illness, poor social support, and depression during the pregnancy all increase the risk of developing the illness
• Postnatal depression needs to be identified and treated promptly and adequately because it can result in a range of lasting adverse outcomes for mother and child
• A range of psychological therapies is effective in treating postnatal depression
• Drugs are also effective and some antidepressants are thought to be safer in breastfeeding mothers than others. But in general the long term outcomes for exposed babies are unknown. Although tricyclic antidepressants have been prescribed for longer, most recent reproductive safety data, which include thousands of exposures, have been for selective serotonin reuptake inhibitors. Because of concerns about toxicity, tricyclics are prescribed less often than selective serotonin reuptake inhibitors for postnatal depression.
• Drugs are recommended for women who decline psychological therapy, or for whom there would be an unacceptable delay in providing non-pharmacological measures.

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Hypothyroidism in adults

Thyroxine structure

By: Bijay Vaidya, consultant endocrinologist and honorary senior clinical lecturer and Simon H S Pearce, professor of endocrinology and honorary consultant physician, Newcastle upon Tyne.
BMJ 28 July 2008

Hypothyroidism is one of the commonest chronic disorders in Western populations. In the United Kingdom, the annual incidence of primary hypothyroidism in women is 3.5 per 1000 and in men 0.6 per 1000.

The management of hypothyroidism is generally considered straightforward and is mostly carried out in primary care in the UK. Cross sectional surveys of patients taking levothyroxine have, however, shown that between 40% and 48% are either over-treated or under-treated.

Furthermore, a small but significant proportion of patients continue to feel unwell despite taking levothyroxine.

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Guillain-Barré syndrome: a clinical review

BMJ, 17 July 2008
By: John B Winer, consultant neurologist, University Hospital Birmingham, UK.

What are the clinical features?

1. All types of Guillain-Barré syndrome present with acute neuropathy, defined as: progressive onset of limb weakness that reaches its worst within four weeks.
2. Typically there are sensory symptoms but few sensory signs.
3. Reflexes are usually lost early in the illness.
4. The respiratory system is affected in a third of cases, but this may not be associated with clear dyspnoea, which makes it more difficult to assess.

Summary points:

• Guillain-Barré syndrome is a rare but important disease that can lead to life threatening respiratory failure. (Guillain-Barré syndrome is a peripheral neuropathy that causes acute neuromuscular failure).
• Misdiagnosis is common and can be fatal because of the high frequency of respiratory failure, which contributes to the 10% mortality seen in prospective studies).
• Structural similarities between a triggering infectious organism and peripheral nerve tissue are important in its pathogenesis
• Treatment consists of rapid administration of intravenous immunoglobulin or plasma exchange, which shortens the time to recovery
• Around 10% of patients die from respiratory failure, pulmonary emboli, or infection
• Around 20% of patients have residual disability, with weakness or persistent sensory disturbance.

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Management of Crohn’s disease

BMJ 2008;336:1062-1066 (10 May).
Clinical Review

By: J R Fraser Cummings, specialist registrar, Satish Keshav, consultant gastroenterologist, Simon P L Travis, consultant gastroenterologist (Gastroenterology Unit, John Radcliffe Hospital, Oxford)

Summary points

• Biological therapies have radically changed the management of Crohn’s disease but must be used judiciously with great awareness of possible adverse events
• Treatment strategies for the disease are rapidly evolving, with immunomodulator and biological therapy being considered in patients who have indicators for developing early severe disease
• Clinical indicators of a poor prognosis (at diagnosis) include perianal or stricturing disease, weight loss >5 kg, or the need for steroids
• Treatment of active disease with mesalazine is little better than placebo; mesalazine is used mainly to reduce the risk of relapse after small intestinal resection
• Access to specialist services, parallel medical and surgical clinics, nurse specialists, dietitians, pharmacists, and other allied professionals is as important as the medication

Publication of standards of care should drive improvement in the care and provision of resources for patients with Crohn’s disease

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Doctors’ education: the invisible influence of drug company sponsorship

BMJ 2008;336:416-417 (23 February).

As calls to end drug companies’ direct sponsorship of doctors’ education echo round the world, an investigation in Australia reveals sponsor involvement in the education of thousands of general practitioners, writes Ray Moynihan, conjoint lecturer, University of Newcastle, New South Wales, and visiting editor, BMJ

• Harvard professor David Blumenthal, an internationally recognised authority on relationships between doctors and drug companies, says that the industry is certainly looking for a return on its investment in medical education.
• “Why would for-profit companies, in this country at least (the United States), pour more than a billion dollars a year into continuing medical education without the expectation of gaining anything from it?” he asks.
• The obvious problem with allowing sponsors to suggest speakers is that they will tend to select speakers who will at best, from the company’s viewpoint, favour their drug or, at least, not contradict the sponsor’s marketing messages.
• The problem is not that individual speakers will change their presentations according to sponsor’s wishes;
• the problem is that doctors attending these sponsored sessions may not be getting the full range of views, in an educational setting supposedly free of industry influence.
• In a landmark paper in 2006 Professor Blumenthal and colleagues called on academic medical centres in the US to end the direct drug company sponsorship of continuing medical education events (also known as continuing professional development).
• In its place they suggested the creation of some sort of blind trust to fund education at an institution level.
• Others, such as Peter Mansfield from HealthySkepticism, a group critical of pharmaceutical marketing, have called for medical education to be funded by the taxpayer through a system of competitive grants.

Perhaps the recent revelations from Australia—and confirmation from the industry itself that it is “not unusual” for sponsors to suggest speakers—will sharpen the lines of debate about how to achieve more independent education or at least greater transparency.

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Diagnosis and management of motor neurone disease

BMJ 2008;336:658-662 (22 March),
Clinical Review;

By: Christopher J McDermott, clinical senior lecturer and honorary consultant neurologist, Pamela J Shaw, professor, University of Sheffield.

Summary points

• Motor neurone disease is relatively uncommon, with an annual incidence of 2 in 100 000; general practitioners may expect to see one or two cases during their career.
• The cause of motor neurone disease is unknown.
• The injury to the nervous system selectively affects the motor neurone cells, sparing other types of cells
• It usually develops in the sixth and seventh decades but can present much earlier; younger presentation is more often seen in familial motor neurone disease, which accounts for about 5% of cases
• Riluzole is the only drug that has a beneficial effect on survival, prolonging life for three or four months
• Non-invasive ventilation, in which the patient uses a mask ventilator system (usually bilateral positive airway pressure) overnight during sleep, has been shown to prolong life and improve quality of life.
• The range of survival is broad, with some patients succumbing to rapidly progressive disease within six months and others living for 10 years or more. Most patients fall somewhere between these extremes. On average people live two to three years after diagnosis.

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Antidepressants an untold story?

BMJ 2008;336:532-534 (8 March)(published 27 February 2008)
By: Jeanne Lenzer, medical investigative journalist, New York.

• New generation antidepressants aren’t all they’re cracked up to be.
• That seems to be the central message in the meta-analysis published this week by Irving Kirsch and colleagues in PLoS-Medicine, and it was this message that made the headlines.
• Kirsch’s conclusion follows on the heels of similar studies showing that statins are useful in only a small subset of patients taking the drugs and earlier studies showing that the safety and performance of cyclo-oxygenase-2 inhibitors seemed better than proved to be the case, further reinforcing previous criticisms that regulators in the United Kingdom and the United States are not doing their duty to protect the public from useless and dangerous drugs.
• But there’s another, deeper problem here—a problem that, ironically enough, was highlighted by GlaxoSmithKline’s news release stating that Kirsch’s conclusions are “incorrect” because he evaluated only a “small subset of the total data available.”
• How can regulators, the public, and doctors know how useful (or how potentially dangerous) drugs really are unless outside researchers have access to all the data?

But do we know the truth about antidepressants even now? Or statins? Or any one of many other drugs currently on the market?

• The answer to that isn’t as simple as it might seem.
• Firstly, there’s the problem of publication bias, the tendency for positive studies to get published and negative studies to be filed away in a drawer. In the case of antidepressants, a 2008 analysis by Erick Turner and colleagues published in the New England Journal of Medicine found that only 8% of antidepressant trials with negative findings were reported as negative, while positive trials were reported as such 97% of the time.
• The problem is not limited to antidepressants, says Turner. A former medical examiner for the FDA, Turner recently told the BMJ that it is critical for researchers to be able to obtain complete study protocols and full datasets to be able determine whether a study’s conclusions are valid.
• His concerns were highlighted by a 1999 study showing that in five top medical journals the authors’ conclusions as stated in journal abstracts either were not supported or were contradicted by data given in the body of the article in 18% to 68% of articles (depending on journal).

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Investigating perianal pain of uncertain cause

BMJ 2008; (16 February).
Practice by: Dr Rebecca Greenhalgh, radiology specialist registrar et al, University College Hospital, London.

• Imaging plays an important role in elucidating the cause of anal pain when the diagnosis is not clinically apparent.
• Endoanal ultrasound is an increasingly available, relatively inexpensive, quick and safe technique providing high resolution images of the anal sphincter complex, and intersphincteric space, but it is limited by a relatively small field of view
• Magnetic resonance imaging, although not universally available, affords much greater anatomical coverage than endoanal ultrasound and can also image the perirectal tissues and lumbar-sacral spine, facilitating diagnosis of conditions beyond the anal canal
• In the case of perianal sepsis, preoperative magnetic resonance imaging may be indicated in clinically suspected complex or recurrent disease to guide surgery, reducing the risk of future recurrence

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Follow-up after breast cancer

BMJ 2008;336:107-108 (19 January),

• More than 1.2 million women and men worldwide are diagnosed with breast cancer each year. In 2007, the 20 year survival rate for breast cancer will be greater than the five year survival rate 30 years ago.
• Breast cancer is now recognised as a chronic disease that can recur even after 20-30 years. Follow-up protocols vary widely—both within and between countries—and are not always evidence based.
• Guidelines from the National Institute for Health and Clinical Excellence (NICE) in England and Wales state that the aims of breast cancer follow-up are to detect and treat local recurrence, to deal with adverse effects of treatment, and to provide psychological support. Routine surveillance for metastatic disease is not recommended.
• The incidence of metastatic disease peaks around two to three years after diagnosis and stays at 2% annually for up to five years before decreasing.
• The NICE guidelines need urgent revision as they do not meet their stated aims. Clinical examination should be annual for two years. Any unit performing more regular clinical assessments should consider amending their protocols now.
• Psychological support should be available and focused when patients’ needs are greatest—not only at diagnosis and during treatment but after treatment ends.
• Our audit data support annual mammograms.
• Timely investigation of symptoms and communication of test results to patients and primary care doctors will help reduce anxiety and improve ongoing care.
• Patients’ needs vary, so follow-up programmes for patients with breast cancer need to be evidence based, flexible, and tailored to their lifelong needs.

By Mr J M Dixon, consultant surgeon and senior lecturer in surgery, Edinburgh.

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