Assessing evidence quality: the GRADE approach
In 2004, a group of international experts in methodology and practice
guidelines first published the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of
evidence supporting medical interventions and develop recommendations. Since then, the group has published a six-part series for clinicians
using GRADE guidelines, and a series of articles supporting systematic review authors and guideline groups using GRADE in their work. Over
100 organisations worldwide — including the World Health Organization, the Cochrane Collaboration, the Joanna Briggs Institute, the American
College of Physicians, DynaMed Plus and UpToDate — have endorsed or adopted GRADE.
Read more in the MJA
GRADE working group website
Effect of aspirin on cardiovascular events and bleeding in the healthy elderly: ASPREE clinical trials
Aspirin is a well-established therapy for the secondary prevention of
cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have
an increased risk. This trial published in the New England Journal of Medicine (NEJM)
enrolled 19,114 community-dwelling
men and women in Australia and the United States who were 70 years of age or older and did not have cardiovascular disease, dementia, or disability.
9525 participants received 100 mg of enteric-coated aspirin, and 9589 received placebo. After a median of 4.7 years of follow-up, the rate of
cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group.
The rate of major haemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively.
Effect of aspirin on disability-free survival in the healthy elderly
Effect of aspirin on all-cause mortality in the healthy elderly
MJA RESEARCH SKILLS – Survival studies: competing risks, immortality & censoring
If time is an integral part of a study, then a key issue is what else
happened to the participants during the time between their recruitment and the time at which we tried to record their outcomes. If we did not
find them, is that because they emigrated or died? If they died, was their death related to their original illness? Did they take some other
therapy in the interim? Time complicates all studies, but most complications can be managed by collecting detailed data on participants over
time and using survival analysis. Find out about survival analysis in this recent latest instalment of the MJA Research Skills
Increasing omega-6 fats reduces total serum cholesterol, but not other blood fat fractions or adiposity
This recent Cochrane review
assessed the effects
of increasing omega-6 fats (linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid) on cardiovascular health, mortality,
lipids and adiposity, using previously unpublished data. 19 RCTs, including 6461 participants who were followed for one to eight years, were included.
The authors found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than myocardial infarction (MI) – where 53 people may
need to increase omega-6 fat intake to prevent 1 person from experiencing MI. High-quality evidence suggests increasing omega-6 fats reduces total serum
cholesterol, but not other blood fat fractions or adiposity.
Early, intense rehabilitation aids recovery after serious traumatic head injury
A review of 11 studies, published in Archives
of physical medicine and rehabilitation
, found that starting rehabilitation early, while people were still in intensive
care – even while still unconscious, and continuing intensive neurorehabilitation, promotes functional recovery and improve outcomes
for people with moderate to severe traumatic brain injury compared with usual care. These effects were replicated based solely on
studies with a low overall risk of bias.
Read NIHR review
MJA RESEARCH SKILLS - Understanding statistical principles in linear and logistic regression
In a recent instalment of the MJA Research Skills
series, the authors introduce the concept of multivariable regression. A regression model establishes the relationship between one or
more exposure, or explanatory, variables and an outcome. The resulting model describes the nature of the relationship between explanatory
variables and outcome, and can be used to predict an unknown outcome value based on given values of the explanatory variables.
Fewer side-effects and similar benefits from shorter chemotherapy after bowel cancer surgery
Guidelines worldwide recommend a six-month combination of a
fluoropyrimidine chemotherapy drug with oxaliplatin, for people with high-risk stage II or III colorectal cancer that has spread through the
bowel wall or to nearby lymph nodes. Side effects of oxaliplatin, including disabling neuropathy, increase with dose. The international SCOT
trial, published in Lancet oncology
, enrolled 6,088 patients and demonstrated similar effectiveness with a three-month
chemotherapy course with the same drugs. Less than half as many patients reported severe neuropathy. Quality of life scores were better with
Read NIHR review
In-hospital 24 hour delay before surgery not a risk factor for complications in patients with acute appendicitis
This meta-analysis of 45 studies (152,314 patients) published in the British
journal of surgery
demonstrates that delaying appendicectomy for presumed uncomplicated appendicitis for up to 24 hours after admission does not
appear to be a risk factor for complicated appendicitis, postoperative surgical-site infection or morbidity.
MJA CLINICAL SKILLS – Bedside cognitive assessment
Cognitive impairment and its related syndromes can be challenging to
diagnose in a short patient encounter. Brief evidence-based assessments of cognition are sensitive, and practical screens can determine if
further testing and intervention are required. For these reasons, cognitive screening is important, as early cognitive impairment can be easily
missed. A recent instalment of MJA Clinical Skills
offers some tips on conducting a brief bedside cognitive examination.
Physiotherapy before abdominal surgery helps prevent pneumonia
A recent Australian and New Zealand study involving adult patients listed for elective upper
abdominal surgery (n=432), published in the BMJ
, found that a 30 minute preoperative physiotherapy session provided within existing
hospital multidisciplinary preadmission clinics halves the incidence of postoperative pulmonary complications and specifically hospital acquired pneumonia. Further
research is required to investigate benefits to mortality and length of stay.
Read NIHR review
Atraumatic needles reduce headaches following lumbar puncture
Use of atraumatic, rather than conventional, needles for lumbar puncture more
than halves the rate of post-procedure headache, according to a recent systematic review of high-quality evidence published in the Lancet
Moreover, this improvement does not come at the expense of procedure success rates. These findings offer clinicians and stakeholders a comprehensive assessment
and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture.
Read NIHR review
RANZCP clinical practice guidelines for mood disorders: Bipolar disorder summary
This guideline summary from the Royal Australian and New Zealand College of
Psychiatrists (RANZCP) published in the MJA
focuses on bipolar disorder. It is intended as an aid to the management of
this complex disorder for primary care physicians working in collaboration with psychiatrists to implement successful long term management.
MJA RESEARCH SKILLS – Guided by the research design: choosing the right statistical test
Choosing the right statistical test or model can be baffling for researchers, and if it
is not conducted correctly, the results from statistical analyses can be misleading. The latest instalment in the MJA Research Skills
series discusses some common medical research designs, ranging from simple to more complicated, and provides an outline of which statistical test to apply in
each instance. In these contexts, data are collected from a sample that is assumed to be representative of a wider population, and the conclusions drawn from the
analyses apply to the wider population.
Stopping biological drugs for rheumatoid arthritis can lead to twice the relapse rate
Drug treatments for rheumatoid arthritis suppress the immune system,
putting people at higher risk of infection. The disease has episodes of improvement and deterioration so judging the effects of treatment can be difficult.
This review published in Annals of rheumatic diseases
aims to inform shared decisions on optimal drug doses to balance
the risk of side effects with the risk of relapse for those wishing to reduce their dose.
Read NIHR review
MJA RESEARCH SKILLS – Distributions and what to do when they are non-normal
Medical researchers often want to find out how medically relevant outcomes
are related to other factors. To do so, they carry out analyses and fit models that are based on assumptions about the nature of the research data.
The latest instalment in the MJA Research Skills
series describes three methods which may be used when one commonly
made assumption is not met. The methods are demonstrated on a real dataset in which the outcome is an index of harmful use of alcohol, with higher
scores indicating a higher incidence of harmful behaviours.
Biological therapies for psoriasis do not increase serious infection risk
People with psoriasis who take an immune-modulating treatment
are no more likely to get serious infections than people taking standard therapies, according to a recent study published in the Journal
of investigative dermatology
. This study used a large database of people with psoriasis from the UK and Ireland. It compared serious
infection risk of the biological therapies – etanercept, adalimumab or ustekinumab (n=5,617) – with non-biological oral therapies (n=3,421). After
accounting for factors such as other illnesses, it found none of the biological therapies studied had a higher risk of infection compared to non-biological
therapies or compared to each other.
Read NIHR review
MJA CLINICAL SKILLS - Spirometry: key to the diagnosis of respiratory disorders
The latest instalment in the MJA Clinical Skills
discusses spirometry. It remains the cornerstone of respiratory function testing and is the key to diagnosing and monitoring the most common respiratory disorders.
Local nerve blocks can improve outcomes for people with hip fracture
Local nerve blocks around the time of hip fracture surgery reduced pain on movement
within 30 minutes of injection. People had less need for opioid pain-relief and were quicker to mobilise after surgery. This updated Cochrane review
identified 31 trials providing moderate to high-quality evidence. The benefits were small but could make a meaningful difference to the patient’s experience and
outcomes. Earlier mobilisation combined with less need for opioids and their associated risk of respiratory depression may have contributed to reduced risk of pneumonia.
Read NIHR review
Using mesh does not improve results in vaginal prolapse surgery
This large pragmatic study published in The Lancet
at over 3000 women with vaginal prolapse. Half of these were randomised; the rest contributed data but were not part of the main evaluation. The study separately
compared synthetic mesh and biological tissue grafts to a repair without these additions. It also took account of whether it was women’s first or subsequent repair
operation. There was no difference in prolapse symptoms or quality of life at two years in women who had surgery that used mesh or biological graft and those who
had standard surgery. About 12% of women overall had minor or major complications from the mesh.
SEE ALSO: Report in 'Health technology assessment' by same authors
Effects of cannabis among adults with chronic pain
Cannabis is increasingly available for the treatment of chronic
pain, yet its efficacy remains uncertain. This systematic review published in Annals of internal medicine
assessed the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain
and general adult populations. From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain in
some patients, but insufficient evidence exists for other types of chronic pain. According to 11 systematic reviews and 32 primary studies,
harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive
impairment. Present research is limited by: few methodologically rigorous trials; cannabis formulations studied may not reflect commercially
available products; and few trials of older, chronically ill populations and patients who use cannabis heavily.
MJA RESEARCH SKILLS - Statistical and clinical significance
In published research, a statistically significant result is often wrongly interpreted as
representing a clinically important finding. In this article – the latest instalment in the MJA
series outlining accessible statistics
for clinicians – the author explores the meanings of statistical and clinical significance.
Allied health professionals have an important role in the treatment of juvenile idiopathic arthritis
Juvenile idiopathic arthritis (JIA) is a chronic, autoimmune, inflammatory joint disease.
It is the most common arthritis in children and adolescents. Pharmaceutical therapy including non-steroidal anti-inflammatory drugs, corticosteroid injections
and biological drugs are the forefront of gold standard care in JIA. Emerging evidence on the non-invasive, physical and mechanical therapies in JIA, suggest
that allied health professionals (AHP) also play an important role as part of this gold standard approach. This paper by local authors, published in the Journal
of paediatrics and child health
, aims to assist AHP in attaining gold standard practice, by providing evidence-based summaries on the presentation
of lower limb pathologies in JIA and the allied health therapies available.
Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration
This recent Cochrane review
included a total of
five RCTs with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C,
vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias. They found that taking vitamin E or
beta-carotene supplements will not prevent or delay the onset of age-related macular degeneration (AMD). The same probably applies to vitamin C
and the multivitamin (Centrum Silver) investigated in the one trial reported to date. There is no evidence with respect to other antioxidant
supplements, such as lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements may have harmful effects, and clear evidence
of benefit is needed before they can be recommended.
SEE ALSO: Cochrane Review on antioxidant vitamin and mineral supplements for slowing the progression of AMD, written by the same review team
Improved Assessment of Chest pain Trial (IMPACT)
A recent study from the Royal Brisbane and Women’s Hospital, published in the MJA
reported that three-quarters of patients presenting to EDs with chest pain could be rapidly assessed using risk stratification tools, early troponin testing and selective objective testing. The
Improved Assessment of Chest pain Trial (IMPACT) included 1366 patients who presented over 3 years with symptoms of suspected acute coronary syndrome (ACS). The researchers found an
overall 30-day ACS rate of 6.6%, none of which occurred in the low risk group. There were 14 ACS cases (1.8%) in intermediate risk patients.
Clinical Practice Guideline: Laparoscopic hysterectomy for benign indications
Since the introduction of minimally invasive gynecologic surgery, the percentage of advanced
laparoscopic procedures has greatly increased worldwide. The Dutch Society of Gynecological Endoscopic Surgery developed a national guideline for laparoscopic
hysterectomy according to the principles of evidence-based medicine in collaboration with clinical librarians. This article published in Archives of gynecology
provides a summary of the main recommendations.
Acupuncture effective for chronic pain in primary care
This synthesis of high-quality data from 18000 patients, published in the UK NIHR journal
Programme grants for applied research
found that acupuncture was more effective than both usual care and sham acupuncture for
chronic pain, consisting of musculoskeletal pain related to the neck and low back, knee osteoarthritis, and chronic headache. Acupuncture also improved quality of
life compared with standard care and was assessed to be a good use of NHS resources.
Read NIHR review
MJA RESEARCH SKILLS – Understanding statistical hypothesis tests and power
The latest instalment in the MJA
outlining accessible statistics for clinicians, co-written by HNELHD staff member John Attia, examines the importance of clinical and biological
science in the construction and clinical interpretation of statistical hypothesis tests.
Higher CVH status is highly beneficial regarding mortality and vascular event risks in the elderly: The Three-City Study
The benefit of ideal cardiovascular health (CVH) on health-related outcomes
in middle-aged patients is firmly established. In the growing elderly population, the high prevalence of comorbidities and medications for chronic
diseases may offset such benefit. This study published in the Journal of the American College of Cardiology
the association of ideal CVH with mortality, incident coronary heart disease, and stroke events in elderly individuals from the community. In subjects
with greater than or equal to 5 metrics at the ideal level – compared with those with less than or equal to 2 – there was a 29% decreased risk of all-cause mortality and 67% for coronary heart
disease and stroke combined.
LOCAL RESEARCH: Azithromycin add-on improves persistent uncontrolled asthma outcomes
Professor Peter Gibson, from the Department of Respiratory and Sleep
Medicine, JHH, and colleagues conducted a randomised, double-blind, placebo controlled parallel group trial to determine whether oral
azithromycin decreases the frequency of asthma exacerbations in adults with symptomatic asthma despite current use of inhaled corticosteroid
and long-acting bronchodilator. 420 patients were randomly assigned to receive azithromycin 500mg or placebo three times per week for 48 weeks.
The study, published in Lancet
, found that patients with asthma symptoms uncontrolled by inhaled corticosteroids and
long-acting bronchodilators had fewer exacerbations of asthma and experienced improved quality of life with the addition of azithromycin.
Low-dose aspirin offers marked reduction in preterm pre-eclampsia in high risk pregnancies
Preterm preeclampsia is an important cause of maternal and perinatal
death and complications. In this multi-centre, double-blind, placebo-controlled trial published in the NEJM
women with singleton pregnancies who were at high risk for preterm preeclampsia were randomly assigned to receive low-dose aspirin (150 mg
per day), or placebo, from 11 to 14 weeks of gestation until 36 weeks of gestation. Preterm preeclampsia occurred in 1.6% of participants
in the low-dose aspirin group, compared to 4.3% in the placebo group. Adherence was good, and there were no significant between-group
differences in the incidence of neonatal adverse outcomes or other adverse events.
MJA RESEARCH SKILLS - Deconfounding confounding Part 2: Using directed acyclic graphs
The latest instalment in the MJA
accessible statistics for clinicians, co-written by HNELHD staff John Attia, continues its discussion of analytical bias — also known as confounding.
Confounding can be induced by a network of variables rather than just a single variable, and adjusting for potential confounders can paradoxically
increase confounding. One of the few true innovations in epidemiological methods has been the emergence of directed acyclic graphs (DAGs) to identify
Which treatment best relieves menopause flushes? Results from the NICE guideline network meta-analysis
Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring
in approximately 75% of postmenopausal women, and are severe in 25%. This review of randomised controlled trials (n = 8326 women), published
, found that for women in natural menopause who have not undergone hysterectomy, transdermal estradiol and
progestogen (O+P) was the most effective treatment for VMS relief, when compared to placebo.
Vitamin D supplementation to prevent acute respiratory tract infections
A recent systematic review and meta-analysis of individual
participant data (n=10,933, aged 0 to 95 years), collected from high quality randomised controlled trials, investigated the overall
effect of vitamin D supplementation on risk of acute respiratory tract infection. The study, published in the BMJ
found that vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants. Patients who were very
vitamin D deficient and those not receiving bolus doses experienced the most benefit.