Exhibit B

Combining Evidence Based Practice resources into a single source of Current Awareness for the Liverpool PCTs.

For Navigation Click Here or go to the bottom of the page

Thursday, January 26, 2006

Post 16: 27 January 2006


Links are given to online full text resources, all other materials can be obtained via the Fade Library, just mail your request to library.services@fade.nhs.uk

Latest Technology Assessments and Appraisals

FOOD: a multicentre randomised trial evaluating feeding policies in patients admitted to hospital with a recent stroke (Dennis) 136 pages, Volume 10, number 2

Study findings did not support routine supplementation of hospital diet for unselected stroke patients who are predominantly well nourished on admission nor did they support a policy of early initiation of percutaneous endoscopic gastrostomy (PEG) feeding in dysphagic stroke patients.


The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease (Loveman) 176 pages, Volume 10, number 1

To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to moderately severe Alzheimer’s disease (AD) and of memantine for moderately severe to severe AD.


The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews (Black) 106 pages, Volume 10, number 3

Computed tomography (CT) screening for lung cancer does not currently meet the accepted National Screening Committee criteria, with no randomised controlled trials and no evidence to support its clinical effectiveness or cost-effectiveness.


Latest Guidelines
NICE (2006) Arrhythmia - implantable cardioverter defibrillators (ICDs) - guidance. London: NICE.

Updated NICE guidance on the use of implantable-cardioverter defibrillators (ICDs) for people at risk of sudden cardiac death (SCD) as a result of cardiac arrhythmias. The guidance, recommends the following categories of patients for an ICD:

  • primary prevention of SCD in the group of individuals who can be identified as being at high risk of SCD either from a number of clinical factors (e.g. previous history of heart attack, heart failure and results of electrical testing of the heart), or, in the presence of specific cardiac abnormalities known to carry a high risk of SCD including people with familial conditions such as long QT syndrome, and hypertrophic caridomyopathy as well as certain types of congenital heart disease.

  • secondary prevention of SCD in individuals who have survived (been resuscitated) a sudden cardiac event.

    • An ICD is a small device, placed beneath the skin of the upper chest below the left shoulder. Leads from the device are passed into the heart to continually sense for a rapid heart rhythm that might cause SCD and deliver a small electric shock to return the rhythm back to normal if necessary.
    Parkinson's disease - full guideline, second consultation

    A clinical practice guideline on Parkinson’s Disease is being developed for use in the NHS in England and Wales. Registered stakeholders for the guideline are invited to comment on the provisional recommendations during the consultation period, which runs until the 21tst February 2005. Publication of the final guideline is expected in June 2006. Please see the links above to access the guideline.
    Latest Reports
    Office for National Statistics (2006) Focus on Health. Basingstoke: Palgrave Macmillan.

    Describes the health of people living in the UK. The data is based on five key areas : health status, risk factors, ill-health, preventive, curative and long-term care services and mortality. Emphasis is placed on trends over time.

    House of Commons Committee of Public Accounts (2006) The NHS Cancer Plan: a
    progress report: Twentieth Report of Session 2005–06: Report, together with formal minutes,
    oral and written evidence. London: TSO.

    The Commons' Public Accounts Committee report on the 10-year Cancer Plan said results were mixed, but that there were major improvements in services. MPs praised the availability of drugs. But criticism came for inequalities in death rates across the UK and lack of effective performance monitoring. The report cited the fact that one in three cancer networks - regional groupings of hospitals, local health managers, councils and the voluntary sector set up to co-ordinate services - had no comprehensive plans in place and monitoring of performance was also said to be "inconsistent". Waiting and staffing targets had been met, the MPs said, but the plan to develop a public awareness campaign about cancer symptoms had not been met. The report also said the Cancer Plan needed to be redrafted because since it was published the NHS has undergone major restructuring with the setting up of 300 primary care trusts, regional strategic health authorities and foundation hospitals.

    Department of Health (2005) Report of the Ad Hoc Advisory Group on the Operation of NHS Research Ethics Committees. London: DoH.

    NHS Research Ethics Committees (RECs) are convened to provide independent advice on
    the extent to which proposals for research studies to be carried out within the NHS comply
    with recognised ethical standards.

    The primary purpose of a REC when considering the proposed study is to protect the
    rights, safety, dignity and wellbeing of all actual or potential participants. Ethics review is
    one of a series of safeguards intended to protect individuals. They are described in the
    Research Governance Framework for Health and Social Care. Research governance is
    intended to enable relevant research of good quality, as well as to forestall inappropriate
    research.

    Ethical approval is therefore only one of the r equirements for initiation of a r esearch
    proposal. The Advisory Group was asked to report on the operation of NHS R esearch
    Ethics Committees and on the inter face with other research approval processes.

    Central Office for Research Ethics Committees (2006) Implementing the recommendations of the Ad Hoc Advisory Group: consultation. London: National Patient Safety Agency.

    Through its Central Office for Research Ethics Committees (COREC), the National Patient Safety Agency (NPSA) has published its consultation on implementing the recommendations of the Report of the ad hoc advisory group on the operation of NHS research ethics committees, an independent report commissioned by the Department of Health. One of the key proposals in the consultation is to reconfigure the research ethics committee system as a more agile research ethics service. This will include the establishment of a new independent group of National Research Ethics Advisers who will ensure that only appropriate proposals for studies are considered by full committees and who will also be able to take some straightforward decisions on their behalf. The consultation ends on the 21st April 2006.
    Department of Health (2006) Best Research for Best Health:A new national health research strategy: The NHS contribution to health research in England. London: DoH.

    Best Research for Best Health outlines the direction that NHS research and development (R&D) will take over the next five years to ensure a vibrant, world-class environment for conducting and using NHS health research.
    Academy of Medical Sciences (2006) Personal data for public good: using health information in medical research. London: Academy of Medical Sciences.

    This report claims that research has been inhibited by confusing regulatory guidance, stifling bureaucracy and unnecessary constraints on researchers’ access to health data. The large numbers treated by the NHS and the use of electronic records should allow the UK to lead the field in analysing health data to allow better understanding and tackling of disease. Instead it has been hidebound by bureaucracy.

    Department of Health (2006) Implementing local commissioning for primary care dentistry - understanding the transitional provisions order: factsheet no. 8. London: DoH.

    The purpose of this factsheet is to explain how the following groups of dentists will transfer to the new contracts:
  • dentists who are working within the “old” general dental services (GDS) system (under section 35 of the NHS Act 1977),

  • dentists with a practice limited to orthodontics, and

  • dentists working in personal dental services (PDS) pilots (under the Primary Care Act 1997)

    • Care Services Improvement Partnership (2006) Women at Risk: The mental health of women in contact with the judicial system. London: DoH.

    Sets out the key findings and recommendations of the work, and in particular the role of the NHS when responsibility for the health of those in custody is fully transferred to PCTs in April 2006. Two key messages underpinning all the recommendations is the need for partnership working within establishments, between government departments, and between statutory and voluntary organisations in the community, and the need to make interventions at an early stage of a woman’s contact with the criminal justice system. This publication has only just become available, although it was originally published on the 6th January 2006.

    Evidence from Journals


    Öngür D
    About 30% of men with schizophrenia or schizoaffective disorders have obsessive-compulsive symptoms
    Evid. Based Ment. Health, Vol.9, No.1, p.28


    Grant BF
    About 26% of people in the US have an anxiety, mood, impulse control, or substance disorder
    Evid. Based Ment. Health, Vol.9, No.1, p.27


    Harpaz-Rotem I
    Young people admitted with self-injury had more severe psychiatric disorders in 2000 than in 1990
    Evid. Based Ment. Health, Vol.9, No.1, p.26


    Schmidt N
    Suicide ideation and attempts are more prevalent in people aged 25–44 years in Australia but become less prevalent in older people
    Evid. Based Ment. Health, Vol.9, No.1, p.25


    Links PS
    History of psychiatric hospital admission increases the risk of suicide less in the very old than in middle aged people
    Evid. Based Ment. Health, Vol.9, No.1, p.24


    Foong J
    Epilepsy or a family history of epilepsy increases the risk of schizophrenia or schizophrenia-like psychosis
    Evid. Based Ment. Health, Vol.9, No.1, p.23


    Becker DR & Drake RE
    Supported employment interventions are effective for people with severe mental illness
    Evid. Based Ment. Health, Vol.9, No.1, p.22


    Terman M
    Review: light therapy is an effective treatment for seasonal affective disorder
    Evid. Based Ment. Health, Vol.9, No.1, p.21


    Blacker D
    Neither vitamin E nor donepezil delays progression from amnestic mild cognitive impairment to Alzheimer’s disease in the long term
    Evid. Based Ment. Health, Vol.9, No.1, p.20


    Gilley DW
    Review: cholinesterase inhibitors reduce burden and care time for informal carers of people with Alzheimer’s disease
    Evid. Based Ment. Health, Vol.9, No.1, p.19


    Burgio L
    Training nursing home care staff to recognise psychopathology improves their ability to identify depressed residents
    Evid. Based Ment. Health, Vol.9, No.1, p.18


    Price DJR
    A structured activity programme reduces depressive symptoms in moderately depressed older men with coronary heart disease, but not women
    Evid. Based Ment. Health, Vol.9, No.1, p.17


    Byrne MK
    Pharmacotherapy and cognitive behavioural therapy: similarly cost effective compared with community referral for disadvantaged women with major depression
    Evid. Based Ment. Health, Vol.9, No.1, p.16


    Muzina DJ
    Divalproex and lithium are similarly cost effective for adults with bipolar disorder
    Evid. Based Ment. Health, Vol.9, No.1, p.15


    Bowden CL
    Cognitive therapy is more cost effective than standard care alone for bipolar disorder
    Evid. Based Ment. Health, Vol.9, No.1, p.14


    Overbeek T & Schruers K
    Cognitive behavioural therapy reduces nocturnal panic in people with panic disorder
    Evid. Based Ment. Health, Vol.9, No.1, p.13


    Grilo CM
    Cognitive behavioural therapy does not improve outcome in obese women with binge eating disorder receiving a comprehensive very low calorie diet programme
    Evid. Based Ment. Health, Vol.9, No.1, p.12


    Isaac MT
    Individual dietary education reduces olanzapine associated weight gain
    Evid. Based Ment. Health, Vol.9, No.1, p.11


    Edlinger M, Fleischhacker WW
    Review: no evidence to support gradual over abrupt switching of antipsychotics
    Evid. Based Ment. Health, Vol.9, No.1, p.10


    Leucht DS, Davis JM
    Intramuscular haloperidol and olanzapine begin to reduce psychosis within 24 hours
    Evid. Based Ment. Health, Vol.9, No.1, p.9


    Kazdin AE
    Multisystemic therapy reduces long term rearrest compared with usual treatment
    Evid. Based Ment. Health, Vol.9, No.1, p.8


    Barton J
    Atomoxetine improves teacher rated symptoms in children with ADHD more than placebo
    Evid. Based Ment. Health, Vol.9, No.1, p.7


    Fombonne E
    Risperidone improves restricted, repetitive, and stereotyped behaviour in autistic children and adolescents
    Evid. Based Ment. Health, Vol.9, No.1, p.6


    Larsen TK
    Poor social and interpersonal functioning prior to diagnosis predicts poor outcome for people with first episode psychosis
    Evid. Based Ment. Health, Vol.9, No.1, p.5


    Latest Questions to the Primary Care Question Answering Service


    ASSESSMENT AND DIAGNOSIS


    A Duke's score is quoted after an exercise ECG test - I know it relates to ST level changes but how is it worked out and what is a 'significant' score?


    How should I interpret a 24 hour BP recording. Is the average reading reasonable to use even if the patient has had a number of high recordings during busy parts of the day ie commuting or getting up?


    When should I investigate a patient in primary care for phaeochromocytoma?


    In any patient with IHD and > 20% CVD risk started on full treatmnet with statins,aspirin,ACE and bblockers what is the new risk of CVD in the next 10yrs ie by how much is the risk lowered in total by all treatments ?


    What are the long term complications on renal function of taking Lithium (for say over 20 years)? How, apart from measuring serum creatinine, should renal problems be monitored in such patients?


    How often should CHD risk be assessed in patients with diabetes?


    We have been asked to diagnose chronic renal failure as part of the new GP contract. Could you give us guidelines as to how to diagnose this and guidelines on how to manage it, given also that the creatinine level acceptable seems to differ with age.



    Do women with previuosly normal smear test results who are no longer sexually active need to continue to have smears? and is there a time scale from last sexual activity where by we would consider stopping?


    Are there guidelines on interpretation of 24 hr BP results?




    CAUSES, RISKS AND PREVENTION


    Do you know of any patient education DVD's (non commercial) that would be suitable for playing in the waiting room, eg brief scenarios about asthma, hypertension, diabetes, flu vacs, childcare etc?


    What is the incidence of penicillin allergy?


    Could you tell me what to suggest in women over 50 who are still taking pop ,how do we establish when it is time to stop contraception?


    What is the antibiotic of choice to treat a case of chlamydia in a breast feeding mother? and what side effects could the baby develop?




    CHILD HEALTH


    What is the antibiotic of choice in a child who has suspected meningitis presenting to general practice, if they are allergic to penicillin? is it iv chloramphenicol?


    Is there any evidence to suggest if infantile colic actually exists and if so, are there any effective remedies ?


    What is the latest guidance for managing suspected epiglotittis in the community whilst waiting for an ambulance; is there a role for steroid or anitiobiotic use?




    NEUROLOGICAL DISEASE


    What interventions are appropriate for a patient with PCOS hoping to start a family in the near future?




    HEALTH MANAGEMENT


    Please define patient care pathways




    MUSCOLOSKELETAL DISEASES


    Should you automatically give calcium and Vit D to someone newly diagnosed as having osteoporosis that you commence on Alendronate?




    GASTROENTEROLOGY


    My patients mother has alpha tripsin1 deficiency and her consultant has asked her daughter to attend for advice & screening. What information do I need to give her?


    Does increasing fibre have any benefit in people suffering from haemorrhoids?




    TREATMENT AND DISEASE MANAGEMENT


    Is there any guidance on the management of HRT withdrawal?




    CARDIOVASCULAR DISEASE


    1) In a patient with AF and previous TIAs on warfarin presenting with suspected angina is aspirin use contraindicated or more beneficial? 2) what is the percentage of haemorrhagic complications with aspirin and warfarin together do the risks outweigh the benefits?




    GENITOURINARY - MALE


    Can you please advise at which hospitals radical prostatectomies are carried out on the NHS.




    RESPIRATORY


    Aerochaber or volumatic in asthma patients, any evidence for or against?



    Hitting the Headlines - Evidence Behind the Press Stories
    Antiviral treatment for avian flu

    Antiviral drugs for influenza may not be effective against avian flu, reported three newspapers (19 January 2006). These articles were based on a systematic review, which found that antiviral drugs eased symptoms of influenza but did not prevent infection. There was no evidence for their use or effectiveness in avian flu.

    • Three newspapers (1-4) reported that there is no evidence that the antiviral drugs Tamiflu and Relenza are effective against avian flu. One of the articles (4) reported that both Tamiflu and Relenza, as well as two additional antiviral drugs, eased the symptoms of influenza but did not prevent infection.

    • The newspaper articles are based on a report of two systematic reviews (5) of randomised controlled trials comparing the efficacy and safety of antivirals with placebo against influenza and asymptomatic influenza. The review found that both the older (amantadine and rimantidine) and newer antiviral drugs (Tamiflu and Relenza) prevented or eased symptoms of influenza but did not prevent infection. None of the investigated drugs was effective against influenza-like illnesses. The two older drugs, amantadine and rimantidine, also caused side effects such as hallucinations and agitation. The review was unable to provide any evidence specific to avian-derived influenza.

    • The main message from the research study that none of the available drugs is likely to be sufficiently effective in the event of an avian-flu pandemic was correctly reflected in all the newspapers. However, three of the newspaper articles were brief and perhaps gave the impression that the research was more specific to avian-derived influenza than it actually was.

    Evaluation of the evidence base for the efficacy of antiviral drugs for avian flu.

    Where does the evidence come from?

    The evidence comes from research led by Dr Thomas Jefferson, based at the Cochrane Vaccines Field, Italy. The study was supported by the UK Department of Health, the Cochrane Review Incentive Scheme 2005, and two ASL grants (ASL19 and ASL20).

    What were the authors' objectives?

    The objective was to assess the efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults.

    What was the nature of the evidence?

    This is based on two systematic reviews of randomised controlled trials of antiviral drugs for the prevention and treatment of influenza. Fifty-two trials comparing the effects of four antiviral agents with control (placebo, no intervention, or symptomatic medication) were included in the review. A comprehensive literature search of several electronic databases, reference lists and contact with the manufacturers and authors of identified studies was used to identify relevant trials. The review studied effects on cases of properly diagnosed influenza (symptomatic or asymptomatic); cases of influenza-like illness, pneumonia, and human influenza caused by avian-derived influenza viruses. It also investigated the effects of the drugs on how infectious people were and for how long (duration and concentration of nasal shedding of viruses or persistence in upper airways). Studies from any part of the world were reviewed.

    What interventions were examined in the research?

    The review included studies that assessed the effects of M2 ion channel blocking drugs (amantadine and rimantadine) and the neuraminidase inhibitors Tamiflu (oseltamivir) and Relenza (zanamivir), used at any dose, preparation or time schedule against influenza and influenza-like illness.

    What were the findings?

    Amantadine and Rimantadine:

    When used to prevent influenza, amantadine was shown to prevent 61% of influenza A cases and 25% of influenza-like illness but it had no effect in preventing asymptomatic cases of influenza. Also, compared with placebo, amantadine was found to increase the odds of side effects (nausea, insomnia and hallucinations) by two-fold. Rimantadine was found to have similar effects.

    When used to treat influenza, compared to placebo, amantadine and rimantadine significantly shortened duration of fever by around a day, but did not stop infected patients being infectious. No data were found for the effect of amantadine or rimantadine specifically on avian-derived influenza.

    Tamiflu and Relenza (Neuraminidase inhibitors):

    When used for the prevention of influenza, compared to placebo, neither Tamiflu (oral) nor Relenza (inhaled) had an effect against asymptomatic influenza or influenza like illness, even at higher doses. The efficacy of Tamiflu 75mg daily against symptomatic influenza was 61% and 73% at 150mg daily. Relenza (10mg daily) was 62% effective.

    When used to prevent influenza in people living in households where someone has already been infected Tamiflu was shown to demonstrate a protective efficacy of 58.5% for households and from 68% to 89% in contacts of index cases. When used for the treatment of patients infected with influenza Tamiflu and Relenza were both associated with shorter times for the alleviation of symptoms and patients were less infectious (viral nasal titres were shown to be significantly reduced). However neither drug stopped patients being infectious irrespective of the dose of the drug.

    No credible data assessing the effect of Tamiflu on avian-derived influenza were found. Data from previous studies relating to Tamiflu were briefly reported on in the discussion. High dose Tamiflu was shown to be effective in preventing lower respiratory tract complications (bronchitis and pneumonia) in influenza cases but not influenza-like illness.

    What were the authors' conclusions?

    The evidence does not support the use of amantadine and rimantadine for influenza. It is also suggested that neuraminidase inhibitors should not routinely be used in the control of seasonal influenza, and should only be used in a serious epidemic or pandemic alongside other public health measures.

    How reliable are the conclusions?

    This was a well conducted review and the authors' conclusions are likely to be reliable. An effort was made to obtain all the relevant information, and when conducting the review appropriate measures were taken to minimise error and bias. The authors were correct to point out that their conclusions are limited by the quality and quantity of the evidence base.

    The review was looking at the effects of antiviral drugs against naturally occurring influenza in healthy adults and the results of the review are applicable to such an illness. The review was unable to provide any evidence specific to avian-derived influenza. Therefore it is unknown if the more effective drugs (Tamiflu or Relenza) would be less or equally effective against avian-derived influenza.

    Systematic reviews

    Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

    There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) or on the Database of Abstracts of Reviews of Effects (DARE).

    References and resources

    1. No evidence flu drugs work-study. The Guardian, 19 January 2006, p1.

    2. Flu fight 'waste' . Daily Mirror, 19 January 2006, p8.

    3. Flu drug warning. The Times, 19 January 2006, p2.

    4. Flu drugs 'will not work' if pandemic strikes. The Guardian, 19 January 2006, p4.

    5. Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet Early Online Publication, 19 January 2006 DOI:10.1016/S0140-6736(06)67970-1.

    Consumer information

    Health Protection Agency - Influenza

    NHS Direct - Avian flu

    Science & development network - Bird flu: the facts

    Previous Hitting the Headlines summaries on this topic

    New drug promises to hit flu where it hurts. Hitting the Headlines archive, 23 January 2003.

    Drug stops flu's spread through families. Hitting the Headlines archive, 14 February 2001.


    Document of the Week from the National Library for Health

    Tramer, M.R., Reynolds, D.J.M., Moore, R.A., McQuay H.J. (1997) Impact of covert duplicate publication on meta-analysis: a case study. BMJ 315:635-64.

    Objective: To quantify the impact of duplicate data on estimates of efficacy.

    Design: Systematic search for published full reports of randomised controlled trials investigating ondansetron's effect on postoperative emesis. Abstracts were not considered.

    Data sources: Eighty four trials (11 980 patients receiving ondansetron) published between 1991 and September 1996.

    Main outcome measures: Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data.

    Results:     Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P<0.00001). n="25)" style="font-weight: bold;">

    Conclusions: By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron's antiemetic efficacy.

    posted by skif at 11:17 am 0 comments

    Thursday, January 19, 2006

    Post 15: 20 January 2006


    Links are given to online full text resources, all other materials can be obtained via the Fade Library, just mail your request to library.services@fade.nhs.uk

    Latest Reports

    Department of Health (2006) Measuring Childhood Obesity: Guidance to Primary Care Trusts. London: DoH.

    Provides advice to primary care trusts (PCTs) on how to measure the height and weight of children aged between 4 and 11 years. Measuring outlined in this guidance is for the purpose of population monitoring. Local data on childhood obesity are needed for the following purposes:

  • To inform local planning and targeting of local resources and interventions.


  • To enable tracking of local progress against the public service agreement target on obesity, and local performance management.


    • House of Commons, Committee of Public Accounts (2005) Department of Health: Tackling cancer: improving the patient journey: Nineteenth Report of Session 2005–06: Report, together with formal minutes, oral and written evidence. London: TSO.

    The report argues that there still needs to be improvement in access to cancer services, particularly for people with prostate cancer.

    Department of Health (2006) Responding to domestic abuse: a handbook for health professionals. London: DoH.

    Gives practical guidance to healthcare professionals on working with patients who may have experienced, or are experiencing domestic abuse. It provides:

  • all readers with an insight into domestic abuse and its effects on individuals, the health service and society;

  • healthcare professionals with practical prompts that they will be able to use in their day-to-day work with women and children;

  • managers and policy-makers with advice on creating strategies for improving the care given to those who have experienced, or are experiencing domestic abuse.


    • Health Protection Agency (2006) HPA National Influenza Summary 2005/2006. London: HPA.

    Influenza activity remained within baseline levels in United Kingdom during weeks 01/06 and 02/06 (week ending 15/01/06). GP consultations for influenza-like illness remained at similar levels to previous weeks with the slightly higher rates recorded amongst those aged between 45-64 years and in northern and central regions.

    Detections of influenza, from specimens collected for routine testing and by sentinel systems, remain at low levels with influenza B representing 80% (N=47) of those positive influenza specimens referred to the Centre for Infections. Influenza B viruses from both the influenza B lineages (B/Yamagata/16/88 lineage and B/Victoria/2/87 lineage), that circulated during the 2004-2005 season, have been detected this season.

    As influenza activity remains at low levels a full evaluation of this season’s influenza vaccine composition should not be made until a significant number of influenza isolates have been collected from the older age groups and other high risk groups that receive the vaccine.

    During week 01/06 the incidence of influenza-like illness in the Netherlands was 66.5 per 100 000 population, which was two times higher than the incidence in week 52/05 (27.1/100 000). Activity elsewhere in Europe, reported by the European Influenza Surveillance Scheme (EISS), remained at baseline levels during weeks 52/05 and 01/ 06.

    Institute for Healthcare Improvement (2006) Saving Accounts; Stories of how health care organisations are saving time, resources, energy and patients’ lives. Cambridge, MA: IHI.

    IHI's 2006 Progress Report contains the extraordinary stories of brave health care institutions that have committed to a new level of performance, along with stories of some of the patients whose lives have been affected by these changes.

    Evidence from Journals

    Pinto BM, Frierson GM, Rabin C, Trunzo JJ, Marcus BH.(2005) Home-based physical activity intervention for breast cancer patients. J Clin Oncol. 2005 May 20;23(15):3577-87.

    PURPOSE: The efficacy of a home-based physical activity (PA) intervention for early-stage breast cancer patients was evaluated in a randomized controlled trial.

    PATIENTS AND METHODS: Eighty-six sedentary women (mean age, 53.14 years; standard deviation, 9.70 years) who had completed treatment for stage 0 to II breast cancer were randomly assigned to a PA or contact control group. Participants in the PA group received 12 weeks of PA counseling (based on the Transtheoretical Model) delivered via telephone, as well as weekly exercise tip sheets. Assessments were conducted at baseline, after treatment (12 weeks), and 6 and 9 month after baseline follow-ups. The post-treatment outcomes are reported here.
    RESULTS: Analyses showed that, after treatment, the PA group reported significantly more total minutes of PA, more minutes of moderate-intensity PA, and higher energy expenditure per week than controls. The PA group also out-performed controls on a field test of fitness. Changes in PA were not reflected in objective activity monitoring. The PA group was more likely than controls to progress in motivational readiness for PA and to meet PA guidelines. No significant group differences were found in body mass index and percent body fat. Post-treatment group comparisons revealed significant improvements in vigor and a reduction in fatigue in the PA group. There was a positive trend in intervention effects on overall mood and body esteem.

    CONCLUSION: The intervention successfully increased PA and improved fitness and specific aspects of psychological well-being among early-stage breast cancer patients. The success of a home-based PA intervention has important implications for promoting recovery in this population.

    Briel M, Christ-Crain M, Young J, Schuetz P, Huber P, Periat P, Bucher HC, Muller B. (2005) Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners. BMC Fam Pract. 2005 Aug 18;6:34.

    Background: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases.

    The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care.

    Methods/Design: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial.

    Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation.

    The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation.

    Discussion: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.

    Moss S, Gray A, Legood R, Vessey M, Patnick J, Kitchener H (2006)Effect of testing for human papillomavirus as a triage during screening for cervical cancer: observational before and after study. BMJ. 2006 Jan 14;332(7533):83-5.

    OBJECTIVE: To assess the effect of introducing testing for human papillomavirus combined with liquid based cytology in women with low grade cytological abnormalities. DESIGN: Observational before and after study. SETTING: Three cervical screening laboratories, England.

    PARTICIPANTS: 5654 women aged 20-64 with low grade cytological abnormalities found at routine cervical screening in a pilot; 5254 similar women in the period before the pilot.

    INTERVENTIONS: Human papillomavirus testing combined with liquid based cytology in the management of women with borderline or mildly dyskaryotic cervical smear results compared with conventional smear tests, with immediate referral to colposcopy of women positive for human papillomavirus.

    RESULTS: 57.9% (3187/5506) of women tested in the pilot were positive for human papillomavirus. The rate of repeat smears fell by 74%, but the rate of referral to colposcopy for low grade cytological abnormalities more than doubled. The estimated negative predictive value of human papillomavirus testing varied between 93.8% and 99.7%.

    CONCLUSION: The addition of testing for human papillomavirus in women with low grade cytological abnormalities resulted in a reduction in the rate of repeat smears, but an increase in rates of referral to colposcopy.

    Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. NEJM 2005 Dec 22;353(25):2643-53.

    BACKGROUND: Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease.

    METHODS: The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee.

    RESULTS: During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or ="0.05)">

    CONCLUSIONS: Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.

    Schwartz RP, Highfield DA, Jaffe JH, Brady JV, Butler CB, Rouse CO, Callaman JM, O'grady KE, Battjes RJ. (2006) A randomized controlled trial of interim methadone maintenance. Arch Gen Psychiatry. Jan;63(1):102-9.

    CONTEXT: Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. OBJECTIVE: To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior.

    DESIGN: Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control.

    SETTING: A methadone treatment program in Baltimore.

    PARTICIPANTS: A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. INTERVENTIONS: Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs.

    MAIN OUTCOME MEASURES: Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment).

    RESULTS: Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. CONCLUSION: Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.

    Rietveld RP, ter Riet G, Bindels PJ, Bink D, Sloos JH, van Weert HC. (2005) The treatment of acute infectious conjunctivitis with fusidic acid: a randomised controlled trial. J Gen Pract. Dec;55(521):924-30.

    BACKGROUND: Acute infectious conjunctivitis is a common disorder in primary care. Despite a lack of evidence regarding the effectiveness of topical antibiotics for the treatment of acute infectious conjunctivitis, most patients presenting in primary care with the condition receive topical antibiotics. In The Netherlands, fusidic acid is most frequently prescribed. AIM: To assess the effectiveness of fusidic acid gel compared to placebo for acute infectious conjunctivitis. DESIGN: Double-blind randomised placebo-controlled trial.

    SETTING: Twenty-five Dutch primary care centres. METHOD: Adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s) were allocated to either one drop of fusidic acid gel 1% or placebo, four times daily during one week. The main outcome measure was the difference in recovery rates at 7 days. Secondary outcome measures were difference in bacterial eradication rates, a survival time analysis of the duration of symptoms, and the difference in recovery rates in culture-positive and culture-negative patients.

    RESULTS: One hundred and eighty-one patients were randomised and 163 patients were analysed. Forty-five of the 73 patients in the treatment and 53 of the 90 patients in the placebo group recovered (adjusted risk difference = 5.3% [95% confidence interval {CI} = -11 to 18]). There was no difference between the median duration of symptoms in the two groups. At baseline, the prevalence of a positive bacterial culture was 32% (58/181). The bacterial eradication rate was 76% in the treatment and 41% in the placebo group (risk difference = 35% [95% CI = 9.3 to 60.4]). In culture positive patients, the treatment effect tended to be strong (adjusted risk difference = 23% [95% CI = -6 to 42]).

    CONCLUSION: At 7 days, cure rates in the fusidic acid gel and placebo group were similar, but the confidence interval was too wide to clearly demonstrate their equivalence. These findings do not support the current prescription practices of fusidic acid by GPs.

    Rosemann T.R., Wensing, M.R., Rueter, G.R. and Szecsenyi .JS. (2006) Referrals from general practice to consultants in Germany: If the GP is the initiator, patients' experiences are more positive. BMC Health Services Research 2006, 6:5.

    Background: Referrals of patients from primary care to medical specialist care are an important activity in any health care system. German data show that the number of referrals by GPs have increased since 2004, but detailed insight into the experiences of patients, GPs and consultants regarding referrals is very limited. This study aimed at describing the experiences of consultants, GPs and patients with referrals from primary care to medical specialist care. An additional objective was to examine the impact of purpose regarding the referral and of the referrer on the experiences of GPs and patients.

    Methods: Referrals of 25 general practitioners (GPs) from 25 practices in Marbach, a rural region in the south of Germany were studied. All adult patients referred after consulting these GPs in a period of five weeks were eligable for the study. GPs, consultants and patients completed short structured forms to document factual characteristics of each referral and their experiences with the referral. GPs and patients completed forms before and after the referral was made, while the consultants completed forms after the patient had consulted them.

    Results: Overall, consultants were very positive about appropriateness of the referral (91%). They were somewhat more critical regarding the information provided on the patients' medical history (61%) and prescriptions (48%). In 258 referrals (63%) GPs perceived clear diagnostic benefits, while in 202 referrals (39%) they perceived clear treatment benefits. GPs' experiences were more positive if the GP's purpose was to reduce diagnostic uncertainty (beta=0.318, p<0.000) or if the purpose was to exclude serious illness (beta=0.143, p<0.010). Other purposes of the referral had no impact on their experiences. Patients' expectations regarding the referrals mostly referred to diagnosis, including increased diagnostic certainty (80%), detailed information about the illness (66%) and exclusion of serious illness (62%). They were overall satisfied with the referral (83%). Their experiences with the referral were more positive if the initiative for the referral came from the physician (beta=0.365, p<0.000).

    Conclusions: Patients, GPs and consultants have positive views on the value of referrals from primary care to medical specialists. Patients were most positive if the physician had initiated the referral, which supports the gate keeper role of the GP.

    Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, Cheuvart B, Espinoza F, Gillard P, Innis BL, Cervantes Y, Linhares AC, Lopez P, Macias-Parra M, Ortega-Barria E, Richardson V, Rivera-Medina DM, Rivera L, Salinas B, Pavia-Ruz N, Salmeron J, Ruttimann R, Tinoco JC, Rubio P, Nunez E, Guerrero ML, Yarzabal JP, Damaso S, Tornieporth N, Saez-Llorens X, Vergara RF, Vesikari T, Bouckenooghe A, Clemens R, De Vos B, O'Ryan M (2006) Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. Jan 5;354(1):11-22.

    BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.

    METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).

    RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).

    CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception.

    Trials

    Latest Questions to the Primary Care Question Answering Service


    CAUSES, RISKS AND PREVENTION


    Will swimming exacerbate Osgood Schlatter's Disease?



    Do you have any dietary advise sheets for people who suffer with gout?



    What evidence is there for the efficacy of calcium and vitamin d in the PREVENTION of osteoporosis in those women at risk?



    In a child under 2 years old undergoing a thoracotomy and lower lobe lobectomy how common is scoliosis as a complication. How severe or disabling is it usually in these cases. Does the scoliosis in these cases result in long term morbidity?



    Can antibiotics cause polyneuritis?



    Is the Influenza vaccination given in the UK in 2005 / 2006 identical to the vaccination given in Belgium this year?



    In patients taking Methotrexate, why is it advised that they should not drink alcohol?



    ASSESSMENT AND DIAGNOSIS


    What percentage of smokers will never develop any symptomatic physiological deficit of lung function?



    A very high percentage of patients after major operations have subclinical DVTs. Is the d-dimer test therefore useful in excluding a DVT after such operations in a patient complaining of ankle swelling, for instance post-hip replacement?



    Is there a standard questionnaire that can be used to gently enquire whether a client is suffering with Erectile Dysfunction?



    What test should be carried out on patients taking methotrexate and how often



    Is a family history of cerebral vascular disease an increased risk factor for coronary vascular disease. Therefore when calculating a CHD risk percentage would the figure be mutiplied by 1.5% if there is a family hx of cva?



    CARDIOVASCULAR DISEASE


    Can patients with history of primary cerebral haemorrage ever have regular aspirin for secondary prevention?



    Should beta-blockers post MI be lifelong? which beta-blocker is best and what dose?



    What is the evidence for using midodrine in the treatment of postural hypotension?



    In a peri-menopausal woman of 40 (non-smoker), who is anxious not to conceive, what are the differing relative risks from VTE of the combined oral contraceptive pill compared with HRT.



    Is there current guidance on how often to routinely check U&E's in patients taking diuretics?



    CANCER


    Is there any value in genetic investigation in cases of asymptomatic patients with a family history of stomach carcinoma?



    MUSCULOSKELETAL DISEASE


    Are there any randomised controlled trials comparing intravenous pamidronate to oral bisphosphonates in the treatment of osteopenia?



    COMPLEMENTARY MEDICINE


    Is there any evidence to show beneficial effects of the alternative medicine Serrapeptase in relation to arthritis. A patient of mine says since she has been taking it shedoesnt need her NSAID . Are there any harmful effects?



    Hitting the Headlines - Evidence Behind the Press Stories

    Aspirin for the prevention of cardiovascular events

    Aspirin lowers the risk of heart problems in men and women in different ways reported two newspapers on 18 January 2006. The newspapers accurately reported the results of a systematic review which should, however, not be regarded as conclusive.
    Two newspapers (1-2) reported that aspirin taken regularly significantly reduced the risk of heart problems in men and women (by 14% and 12%, respectively) but in different ways. In men, the risk of heart attacks is reduced by 32%, and in women the risk of stroke is reduced by 17%. Both newspapers also note that aspirin is also associated with an increase in major bleeding.
    The newspaper articles were based on a systematic review (3) of six trials involving 95456 people (54% women) without existing cardiovascular disease. After an average of 6.4 years, the risk of cardiovascular events (heart attack, stroke, or death from these causes) was 14% lower in men and 12% lower in women taking aspirin compared to those not receiving the drug. Looking at the three event categories separately, only the risk of heart attack was significantly reduced in men (by 32%) and only the risk of stroke was significantly reduced in women (by 17%). There was no effect on rate of death detected in either men or women. The effects on heart attack and stroke are based on relatively small numbers of events.
    The newspapers reported the results of the research accurately. However the front page story in the Daily Express (1) overstated the positive findings of the study by incorrectly saying that the research showed that aspirin could be a 'lifesaver'.
    Evaluation of the evidence base for aspirin in the prevention of cardiovascular events in women and men

    Where does the evidence come from?

    The research was conducted by a team from the USA and Italy led by Dr DL Brown, based at the State University of New York.

    What were the authors' objectives?

    To determine if the benefits and risks of aspirin in the primary prevention of cardiovascular disease are different in men and women.

    What was the nature of the evidence?

    This was a systematic review of randomised controlled trials assessing aspirin for the prevention of cardiovascular disease, and reporting cardiovascular death, myocardial infarction and stroke and major bleeding as outcomes. Six trials involving 95456 participants (51342 women and 44114 men) were included in the review. Three trials included only men and one included only women. Three trials were in apparently healthy health care professionals, and 3 included individuals with risk factors for cardiovascular disease.

    What interventions were examined in the research?

    Aspirin therapy, with dosage ranging from 100 mg every other day to 500 mg daily, was compared with placebo. The mean duration of therapy at follow-up ranged from 3.6 years to 10.1 years.

    What were the findings?

    Aspirin significantly reduced the odds of major cardiovascular events (cardiovascular death, myocardial infarction or stroke) by 12% in women and 14% in men.
    In women, aspirin had no significant effect on the rate of myocardial infarction, but significantly reduced the odds of stroke by 17%. Considering stroke subtypes, there was a significant 24% reduction in the odds of ischemic stroke but no significant effect on hemorrhagic stroke.
    In men, aspirin significantly reduced the odds of myocardial infarction by 32%. Although aspirin did not have a significant effect on all strokes or ischemic stroke, it was associated with a significant 69% increase in the odds of hemorrhagic stroke.
    In both men and women aspirin had no significant effect on total mortality or deaths from cardiovascular causes.
    In both men and women aspirin was associated with significantly increased odds of major bleeding of 70%.

    What were the authors' conclusions?

    The authors concluded that in both women and men, aspirin therapy reduced the risk of a composite of cardiovascular events. In women this was due to its effect on reducing the risk of ischemic stroke and in men it was due to a reduction in the risk of myocardial infarction. Aspirin significantly increased the risk of bleeding to a similar degree among men and women.

    How reliable are the conclusions?

    This systematic review appears to have been generally well conducted. However, the statistical power of the analyses may have been limited, particularly those considering the different categories of cardiovascular event. This was because the number of trials included in some of the comparisons was small and also because the outcomes studied (cardiovascular death, myocardial infarction and stroke and major bleeding) are relatively rare. Therefore, the indicated differences in effects in men and women should be considered with caution. Also it is possible that the apparent differences in the effect of aspirin in men and women may mainly reflect the difference in how common myocardial infarction and stroke are in men and women, rather than any real difference in its effect. The authors themselves suggest that further studies are needed to confirm the gender differences.

    Systematic reviews

    Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.
    There were two related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) (4-5) and three on the Database of Abstracts of Reviews of Effects (DARE) (6-8).

    References and resources

    1. Miracle aspirin. New proof that it prevents heart attacks and strokes. Daily Express, 18 January 2006, p1,4.
    2. Aspirin, the heart tonic for both sexes. Daily Mail, 18 January 2006, p24.
    3. Berger JS, Ronacaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295(3):306-313.
    4. Hankey GJ, Sudlow CLM, Dunbabin DW. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. The Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD001246. DOI: 10.1002/14651858.CD001246.
    5. Jackson PR, Aarabi M, Wallis JE. Aspirin for primary prevention of coronary heart disease. (Protocol). The Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004586. DOI: 10.1002/14651858.CD004586.
    6. Eidelman R S, Herbert P R, Wiesman S M, Hennekens C H. An update on aspirin in the primary prevention of cardiovascular disease. Archives of Internal Medicine 2003;163(17):2006-2010. [DARE Abstract]
    7. Hayden M, Pignone M, Phillips C, Mulrow C. Summary of the evidence: aspirin for the primary prevention of cardiovascular events. Rockville, MD, USA: Agency for Health Care Policy and Research 2002:33. [DARE Abstract]
    8. Boltri J M, Akerson M R, Vogel R L. Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic review of all-cause mortality. Journal of Family Practice 2002;51(8):700-704. [DARE Abstract]
    Consumer information
    British Heart Foundation
    NHS Direct - Heart Attack Prevention
    Healthy Heart

    "Drug meant to stop early birth 'brings it on instead'"

    A drug given to pregnant women to prevent premature birth has been found to double the risk, reported five newspapers (13 January 2006). The newspapers were generally accurate in reporting that a well-conducted trial found that metronidazole does not reduce, and may increase early preterm birth in high risk women.

    Five newspapers (1-5) reported that metronidazole, an antibiotic given to around one in 200 pregnant women to prevent premature birth, increases the risk of premature birth.

    The research (6) was a well-conducted double blind randomised controlled trial, in which 100 pregnant women at high risk of preterm delivery were randomised to receive either metronidazole or placebo for one week. There was no difference in the proportion of women delivering before 30 weeks gestation between the metronidazole and placebo groups. However, significantly more women in the metronidazole treated group delivered before 37 weeks gestation than in the placebo group (62% and 39% respectively). The authors' concluded that metronidazole does not does not reduce and may increase early preterm birth in high risk pregnant women.

    The newspapers were generally accurate in their reporting of the trial, however one newspaper reported that the number of premature babies born as a result of the drug was more than 1,000 over the last month (1), whilst the other newspapers reported the figure to be around 1,000 per year (2, 3, 4, 5). This figure was not reported in the research study. Although the authors' conclusion seems to be supported by the research, only 100 women were randomised, therefore, the trial may have been underpowered and unable to detect statistically significant differences in some outcomes between groups.

    Evaluation of the evidence base for metronidazole for the prevention of preterm birth in women at high risk.

    Where does the evidence come from?

    This multi-centre trial was conducted at fourteen UK hospitals, led by Professor Andrew Shennan of the Maternal and Fetal Research Unit at St Thomas' Hospital in London. The study was funded by Tommy's the baby charity, who had no involvement in the study.

    What were the authors' objectives?

    The objective was to determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy.

    What was the nature of the evidence?

    The study was a double blind, randomised placebo controlled trial involving 892 asymptomatic
    pregnant women who were at between 23 and 24 weeks of gestation, with a singleton pregnancy, and who were at high risk of pre-term birth (history of previous preterm birth or preterm prelabour rupture of membranes, previous late miscarriage, uterine anatomical abnormality, prior cervical surgery or current cervical cerclage). Gestational age was confirmed by obstetric ultrasound. Women were excluded if they had been prescribed metronidazole within four weeks prior to study recruitment. Randomisation was computer-generated by the trial statistician and sent to a commercial packaging company to pre-package and label the tablets. The tablets were identical, sealed in opaque containers and dispensed by local pharmacies independent of the investigators and attending clinicians. Randomisation was stratified by clinic and week of gestation when the positive fFN result was obtained.
    A sample size calculation determined that 420 women with positive fFN tests were required to detect a statistically significant difference between metronidazole and placebo groups. Outcome data were collected from maternity records and hospital computer databases, using trial-specific data collection forms.

    What interventions were examined in the research?

    Women were screened at 24 weeks and 27 weeks gestation for presence of fFN in cervicovaginal secretions, which is used to predict risk of preterm delivery. One hundred women with a positive result at the 24 or 27-week fFN test were randomised to receive either metronidazole 400mg three times daily for seven days, or indistinguishable placebo. Women were asked to record the time and date that they took each tablet and asked to return the tablet packaging, in order to assess their compliance. The fFN test was repeated at 30 weeks gestation.
    The primary outcome measure was delivery prior to 30-week gestation; secondary outcome measures included delivery prior to 37-week gestation and parameters of neonatal outcome. Interim analyses were performed after each 50 women were recruited.

    What were the findings?

    The study was stopped early due to difficulty in recruitment. 892 women were tested for fFN status and 730 tests were repeated at 27 weeks. 116 pregnancies tested positive on either the 24 or 27-week test and 100 women accepted randomisation. Compliance with medication was good, with 75% of women returning their records; of which only seven missed any dose. Women in the intervention and control groups were comparable, except for number of qualifications; those in the placebo group were statistically significantly more likely to have left school with fewer qualifications.

    Following treatment the 30-week fFN test result reverted to negative in 48% women randomised to metronidazole and 50% women randomised to placebo. Antenatal admissions were more frequently recorded in the metronidazole group, however the length of stay was similar between groups.

    There was no statistically significant difference in the proportion of women who delivered before 30 weeks gestation between the metronidazole and placebo groups. Statistically significantly more women in the metronidazole treated group delivered before 37 weeks gestation than in the placebo group (62% and 39% respectively). In a subgroup analysis, statistically significantly more women in the metronidazole group had spontaneous onset of labour (rather than indicated delivery) before 37 weeks gestation than in the placebo group (79% and 50% respectively). There were no statistically significant differences in birthweight, 1- and 5-minute Apgar scores, Special Care Baby Unit admissions or survival between the metronidazole and placebo groups.

    What were the authors' conclusions?

    The authors concluded that metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test and that preterm birth may be increased by metronidazole therapy.

    How reliable are the conclusions?

    The authors' conclusions are supported by the findings of this well conducted trial. Randomisation, concealment of allocation and blinding procedures appear to have been appropriate. There were no significant differences between women assigned to the two treatment groups, other than number of qualifications. Compliance with medication was reported as being good. The outcomes measured were clinically relevant and systematically collected. Statistical analyses appear to have been appropriate. The sample size calculation determined that 420 women with positive fFN tests would be required to detect a statistically significant difference between the metronidazole and placebo groups. However, only 116 women with positive tests were recruited, of which 100 were randomised, therefore, the trial may have been underpowered and unable to detect statistically significant differences in some outcomes between groups.

    Systematic reviews

    Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.
    There were four related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) (7-10) and four on the Database of Abstracts of Reviews of Effects (DARE) (11-14). However these reviews investigated antibiotics in general, including metronidazole, rather than specifically investigating metronidazole alone.

    References and resources

    1. Birth-delay drugs that don't work. Daily Express, 13 January 2006, p40.
    2. Pregnancy drug 'doubles risk of premature birth'. Daily Mail, 13 January 2006, p9.
    3. Labour-delaying drug linked to 1,000 pre-term babies a year. The Guardian, 13 January 2006, p8.
    4. Premature baby drug doubles risk. Daily Telegraph, 13 January 2006, p1.
    5. Drug meant to stop early birth 'brings it on instead'. The Times, 13 January 2006, p5.
    6. Shenan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, et al. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG: An International Journal of Obstetrics and Gynaecology 2006;113(1):65-74.
    7. King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. The Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD000246. DOI: 10.1002/14651858.CD000246.
    8. Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P. Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality. The Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD002250. DOI: 10.1002/14651858.CD002250.
    9. Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of membranes. The Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD001058. DOI: 10.1002/14651858.CD001058.
    10. McDonald H, Brocklehurst P, Parsons J. Antibiotics for treating bacterial vaginosis in pregnancy. The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD000262. DOI: 10.1002/14651858.CD000262.pub2.
    11. Egarter C, Leitich H, Husslein P, Kaider A, Schemper M. Adjunctive antibiotic treatment in preterm labor and neonatal morbidity: a meta-analysis. Obstetrics and Gynecology 1996;88(2):303-309. [DARE Abstract]
    12. Koumans E H, Markowitz L E, Hogan V. Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: a synthesis of data. Clinical Infectious Diseases 2002;5(Supplement 2):S152-S172. [DARE Abstract]
    13. Leitich H, Brunbauer M, Bodner-Adler B, Kaider A, Egarter C, Husslein P. Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis. American Journal of Obstetrics and Gynecology 2003;188(3):752-758. [DARE Abstract]
    14. Riggs M A, Klebanoff M A. Treatment of vaginal infections to prevent preterm birth: a meta-analysis. Clinical Obstetrics and Gynecology 2004;47(4):796-807. [DARE Provisional Abstract]
    Consumer information
    National Childbirth Trust
    Tommy's: the baby charity

    "New cervical test 'not any better'

    Liquid-based cytology cervical cancer screening method is no better than the conventional Papanicolaou (Pap) smear test, reported two newspapers (13 January 2006). The newspapers reflected the conclusions of the systematic review (3), however, this review has some limitations regarding study quality, potential bias and generalisability.


    • On 13th January 2006, two newspapers (1,2) reported that the liquid-based cytology screening method for cervical cancer, was no better than the conventional Pap smear test.

    • The research, published in the Lancet (3), was a systematic review, which included 56 primary studies. The studies examined the results of over a million slides. The results showed that there was no evidence that liquid-based cytology either reduced the proportion of unsatisfactory slides, or had greater accuracy in detecting higher-grade lesions, than conventional cytology.

    • The newspaper reports generally provided an accurate report of the authors' conclusions. However, the studies included in the main analysis of the review varied greatly, both clinically and statistically. In addition, there were limitations regarding the quality of included studies, potential for publication bias, and the exclusion of studies using automated systems, which may impact on the reliability and generalisability of the results. The authors' conclusion that large randomised controlled trials are needed is supported.

    Evaluation of the evidence base for the comparative performance of cervical cytology techniques

    Where does the evidence come from?

    The systematic review was conducted by researchers from the Screening and Test Evaluation Program, and Victorian Cytology Service in Australia, led by Dr Davey. The research was part funded by the National Health and Medical Research Council of Australia.

    What were the authors' objectives?

    To compare the performance of liquid-based cytology for screening for cervical cancer, with that of conventional cytology.

    What was the nature of the evidence?

    The study was a systematic review, which included 56 primary studies. The authors searched two electronic bibliographic databases and the reference lists of included studies and previous reviews for studies published in peer-reviewed journals.

    What interventions were examined in the research?

    Studies that described a direct comparison between two cytology techniques for screening for cervical cancer; liquid-based cytology and conventional cytology, with results for both being read using manual techniques (and not an automated screening system), were reviewed. Liquid-based cytology and conventional cytology were compared in terms of the proportion of slides classified as unsatisfactory, the proportion of slides classified in each cytology category, and the accuracy of detection of high-grade disease. An overall pooled difference was calculated using a random effects meta-analysis. Further analyses were conducted taking into account study design, quality and setting. The sensitivity and specificity of tests were calculated where possible, to investigate the accuracy of the two techniques.

    What were the findings?

    The authors classified five studies as high quality, 32 as medium quality and 19 as low quality. None of the studies randomly assigned women to the two techniques evaluated, however the five studies that were considered high quality were paired sample studies.

    In the 46 studies that provided information on percentages of unsatisfactory slides, 3,646 of 483,050 (0.75%) of the liquid based cytology slides, and 5,389 of 662,401 (0.81%) of the conventional cytology slides were considered unsatisfactory. The proportional difference in the number of unsatisfactory slides between the two techniques ranged from -10.8 to 8.9%. When results from these studies were pooled, the difference in the number of unsatisfactory slides between the two techniques was -0.14%, and not statistically significant.

    Analysis showed that overall there was no statistically significant difference in the median differences in the proportion of unsatisfactory slides, when the studies were stratified according to study design, quality or setting.

    Four of the 37 high and medium quality studies provided sufficient data to calculate sensitivity and specificity. None of the studies provided evidence that liquid-based cytology improved accuracy in the detection of high-grade disease.

    What were the authors' conclusions?

    The authors concluded that there was no evidence that liquid-based cytology reduced the proportion of unsatisfactory slides, or detected more high-grade lesions in high quality studies than conventional cytology. They also stated that large randomised controlled trials are needed.

    How reliable are the conclusions?

    The review was appropriately conducted with regard to study selection, quality assessment and data extraction, with each of these being carried out in duplicate. Two electronic databases were searched and only studies published in peer-reviewed journals were included, therefore there is a potential for publication bias. The pooling of results in a meta-analysis of studies that varied so much, both clinically and statistically, may not have been appropriate. The results seem to support the conclusion that there is no evidence to suggest that liquid-based cytology reduced the proportion of unsatisfactory slides compared to conventional cytology. However, the limitations regarding the quality of included studies, potential for publication bias, and the exclusion of studies using automated systems should be kept in mind.

    Systematic reviews

    Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

    There was one related systematic review (4) and one review which is currently being completed and will be available in the future (5) identified on the Cochrane Database of Systematic Reviews (CDSR). There were four related reviews identified on the Database of Abstracts of Reviews of Effects (DARE) (6-9).

    References and resources

    1. New cervical test 'not any better'. Daily Telegraph, 13 January 2006, p2.

    2. Doubts over new smear test. The Times, 13 January 2006, p5.

    3. Davey E, Barratt A, Irwig L, Chan SF, Macaskill P, Mannes P, Saville AM. Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review. Lancet 2006;367:122-132.

    4. Forbes C, Jepson R, Martin-Hirsch P. Interventions targeted at women to encourage the uptake of cervical screening. The Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD002834. DOI: 10.1002/14651858.CD002834.

    5. Koliopoulos G, Martin-Hirsch P, Paraskevaidis E, Arbyn M. HPV testing versus cervical cytology for screening for cancer of the uterine cervix. (Protocol). The Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD004709. DOI: 10.1002/14651858.CD004709.

    6. Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, van Ballegooijen M, van den Akker E. A systematic review of the role of human papillomavirus testing within a cervical screening programme. Health Technology Assessment 1999;3(14):1-204. [DARE Abstract]

    7. Australian Health Technology Advisory Committee. Review of automated and semi-automated cervical screening devices. Canberra, ACT, Australia: Commonwealth Department of Health and Family Services 1998. [DARE Abstract]

    8. Buntinx F, Brouwers M. Relation between sampling device and detection of abnormality in cervical smears: a meta-analysis of randomised and quasi-randomised studies. BMJ 1996;313:1285-1290. [DARE Abstract]

    9. Nanda K, McCrory D C, Myers E R, Bastian L A, Hasselblad V, Hickey J D, Matchar D B. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Annals of Internal Medicine 2000;132(10):810-819. [DARE Abstract]

    10. Payne N, Chilcott J, McGoogan E. Liquid-based cytology in cervical screening: a rapid and systematic review. Health Technology Assessment 2000;4(18).

    11. Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, Brewer N. Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis. Health Technology Assessment 2004;8(20).

    Consumer information

    CancerBACUP: Cervical cancer information centre

    NHS Direct: Cancer of the cervix

    Cancer Research UK

    Previous Hitting the Headlines summaries on this topic

    'Vaccine for cervical cancer'. Hitting the Headlines archive, 7 October 2005.

    Cervical cancer vaccine 'in two years'. Hitting the Headlines archive, 7 April 2005.

    'Vaccine for cervical cancer'. Hitting the Headlines archive, 2 February 2005.

    'Vaccine hope over cervical cancer'. Hitting the Headlines archive, 12 November 2004.

    'Vaccine to beat cervical cancer'. Hitting the Headlines archive, 29 October 2004.

    A vaccine for cervical cancer? Hitting the Headlines archive, 20-21 November 2002.



    Electric shock and drugs for the treatment of depression

    Electric shock therapy and drugs are the best treatment response to depression reported two newspapers (13 January 2006). The newspaper articles were based upon an overview of recent developments and current controversies in the treatment of depression that was not conducted using systematic methodology.


    • Two newspapers (1,2) (13 January 2006) report that anti-depressants and electroconvulsive therapy (ECT) are still the best way to treat depression, according to a paper in the Lancet.(3) Both newspapers focussed upon the authors statements, as emphasised in the Lancet press release,(4) regarding the effects of ECT and the use of antidepressants.

    • The article, which was published in the 'Seminar' section of the Lancet, was an overview of recent developments and current controversies in the management of depression. This was not a systematic review of all the evidence regarding the effects of either ECT or antidepressant therapy. Although a number of electronic databases had been searched to identify relevant literature, this was then used, in line with the aims of the review, to illustrate the "recent developments and current controversies in depression".

    • The newspaper articles accurately summarised the statements made on the effectiveness of ECT and antidepressant therapy and recent public concerns about potential side effects as presented in the Lancet press release. However, neither of the newspapers stated that their articles were based upon an overview written to stimulate debate in the field, rather than a specific piece of research.

    • There are a number of systematic reviews that have assessed the effects of both ECT and antidepressant therapy in the treatment of depression (see below for details).

    Systematic reviews

    Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

    There were two related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) (5-6) and three related reviews on the Database of Abstracts of Reviews of Effects (DARE) (7-9).

    References and resources

    1. Electric shock treatment 'best response' to depression. The Guardian, 13 January 2006, p14.

    2. Electric shock and drugs 'are best hope for depressives'. The Times, 13 January 2006, p16.

    3. Ebmeier KP, Donaghey C, Steele JD. Recent developments and current controversies in depression. Lancet 2006;367:153-167.

    4. Antidepressants and electroconvulsive therapy are the best treatment options for depression. Lancet press release, 13 January 2006.

    5. Van der Wurff FB, Stek ML, Hoogendijk WL, Beekman ATF. Electroconvulsive therapy for the depressed elderly. The Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD003593. DOI: 10.1002/14651858.CD003593.

    6. Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J. Selective serotonin reuptake inhibitors (SSRIs) versus other antidepressants for depression. The Cochrane Database of Systematic Reviews 1999, Issue 4. Art. No.: CD001851. DOI: 10.1002/14651858.CD001851.

    7. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003;361:799-808. [DARE Abstract]

    8. Kho K H, van Vreeswijk M F, Simpson S, Zwinderman A H. A meta-analysis of electroconvulsive therapy efficacy in depression. Journal of ECT 2003;19(3):139-147. [DARE Abstract]

    9. University of Newcastle upon Tyne. Centre for Health Services Research; University of York. Centre for Health Economics. The choice of antidepressants for depression in primary care. Newcastle upon Tyne: University of Newcastle upon Tyne, Centre for Health Services Research 1998:67. [DARE Abstract]

    10. Improving the recognition and management of depression in primary care. Effective Health Care 2002;7(5):1-12.

    11. Greenhalgh J, Knight C, Hind D, Beverley C, Walters S. Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies. Health Technology Assessment 2005;9(9).

    Consumer information

    MIND

    Mental Health Foundation

    Depression Alliance

    Previous Hitting the Headlines summaries on this topic

    Seroxat and the risk of suicide. Hitting the Headlines archive, 22 August 2005.

    'Antidepressants 'little better than placebos'. Hitting the Headlines archive, 21 July 2004.

    Antidepressants and the risk of suicide. Hitting the Headlines archive, 21 July 2004.

    Therapy beats pills if you are miserable. Hitting the Headlines archive, 3 December 2000.


    Added value of a clinical decision support system when combined with a community intervention.

    This study in the Journal of the American Medical Association, compared the sole use of a community intervention with the use of the community intervention combined with a clinical decision support system to assist with the prescribing of antimicrobial drugs for acute respiratory tract infections.

    The results showed that antimicrobial prescribing decreased with the combined intervention, thus demonstrating that the clinical decision support system added value to the community intervention.

    What's New from the National Library for Health

    posted by Kieran at 8:35 am 0 comments

    Site Index

    Contributors

    • Tracy
    • Kieran

    Links

    • Fade Library
    • Fade Health News Current Awareness
    • National Library for Health
    • Aditus

      Previous Posts

      • Post 24: 24 March 2006
      • Post 23: 17 March 2006
      • Post 22: 10th March 2006
      • Post 21: 3rd March 2006
      • Post 20: 24th February 2006
      • Post 19: 17th February 2006
      • Post 18: 10 February 2006
      • Post 17: 3rd February 2006
      • Post 16: 27 January 2006
      • Post 15: 20 January 2006

      Archives

      • September 2005
      • October 2005
      • November 2005
      • December 2005
      • January 2006
      • February 2006
      • March 2006

      Powered by Blogger

    Tag Cloud: Site Navigation.

    Tag clouds show tags used to identify posts with particular content.

    The more frequently a word is used to describe content, the larger it will be displayed within the cloud.

    Just click on a word to see which posts have been tagged using that term