Making Education Easy
Issue 87 – 2014
Welcome to the eighty-seventh issue of GP Research Review.
The use of antibacterial prophylaxis to prevent urinary tract infection (UTI) recurrences in children with vesicoureteral
Prophylactic antibacterials prevent
reflux (VUR) remains controversial. However, unequivocal evidence published recently in the NEJM has attested to
the benefits of such treatment. The research involved children (aged 2–71 months) who were diagnosed with VUR
UTI recurrences in VUR
following a first or second episode of UTI. Those who were treated with trimethoprim/sulphamethoxazole over a
Intensification of metformin with
2-year period to prevent infections were far less likely to have recurrent UTI compared with those who received
insulin linked to CV events
placebo. Moreover, certain subgroups of children derived more benefit than others from antibacterial prophylaxis, particularly those with bladder and bowel dysfunction at study entry, and those who had a fever with their initial UTI.
How GPs want to learn in the
A large, prospective cohort study from France suggests that premenopausal women who have "very many" moles may
have a significantly higher risk of breast cancer than women who have no moles. Perhaps in future screening scores for breast cancer will include number of moles as an important marker.
Changes in healthcare policy can
The PrediMed study from Spain shows that an increase in extra virgin olive oil and nut intake in the context of a
adversely impact medication use
Mediterranean diet results in fewer adverse cardiovascular (CV) events (stroke, myocardial infarction, and CV death).
L-thyroxine therapy in subclinical
The higher the daily olive oil intake, the greater the risk reduction.
I hope you enjoy this issue and I welcome your comments and feedback. Kind Regards
The value of radiography in knee
Associate Professor Jim Reid
Refuting aspirin for prevention of
Moles linked to breast
Antimicrobial prophylaxis for children with vesicoureteral reflux
Authors: RIVUR Trial Investigators
Extra virgin olive oil good for the
Summary: The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial enrolled 607 children
aged 2–71 months who were diagnosed with vesicoureteral reflux (VUR) following a first or second episode of urinary
Ginger for nausea and vomiting
tract infection (UTI). The children were randomised to receive trimethoprim/sulphamethoxazole or placebo. Recurrent
in early pregnancy
UTI developed in 39 of 302 children (13%) who received prophylaxis as compared with 72 of 305 children (24%) who received placebo (relative risk 0.55; 95% CI, 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio [HR] 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (HR 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (HR 0.21; 95% CI, 0.08 to
Abbreviations used in this issue
0.58). The occurrence of renal scarring did not differ between the groups (11.9% for the prophylactic group and 10.2%
CVD = cardiovascular disease
for the placebo group). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates
OA = osteoarthritis
that were resistant to trimethoprim/sulphamethoxazole was 63% in the prophylaxis group and 19% in the placebo group.
UTI = urinary tract infection
VUR = vesicourecteral reflux
Comment: This study has a "yes/but" result. The risk of recurrence of infection was essentially halved with
prophylaxis, but in the group whose first recurrence was caused by E. coli, there was a high (63%) development
of resistance to trimethoprim/sulphamethoxazole. There was no difference in the development of renal scarring between the placebo and prophylactic group. The real conclusion is that the cause of the vesicoureteral reflux should be primarily addressed.
Reference: N Engl J Med 2014;370(25):2367-76
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GP Research Review
How do GPs want to learn in the digital era?
intensification of metformin
Authors: Yee M et al.
treatment with insulin
Summary: A total of 2500 GPs in Australia participated in a national survey conducted in 2012 that questioned
vs sulfonylureas and
their preferences for continuing medical education (CME) activities and motivation for choice. The vast majority (95%) preferred learning in a group rather than on their own. The analysis identified that 83% preferred face-
cardiovascular events and all-
to-face lecture-based formats, 70% preferred interactive group discussions, 66% preferred one-to-one learning
cause mortality among patients
with an expert, and 55% preferred online self-education. Relevance to clinical practice was the key motivation for participation (80%).
Roumie CL et al.
My feeling is that we are in a transition period. The oldies (that's me – though I am barely run-in)
"learned" by listening to pearls of wisdom being dropped from above in lectures. Damned if I can remember
Summary: Data were retrospectively analysed from the
much from lectures I have attended. The problem is that there are many ways that people learn and we are
national Veterans Health Administration, Medicare, and
all individuals. What is apparent from someone who has spent his whole professional life in medical education
National Death Index databases, which included 178,341
is – to teach is not to ensure learning occurs; to learn does not necessarily mean understanding occurs, and
veterans with diabetes initially treated with metformin from
understanding is not to do; but to do and understand is to remember. We all do this in different ways and
2001 through 2008 who subsequently added either insulin
in another 10 years when a new generation of doctors is upon us we will continue to advance our learning
(n=2948) or a sulphonylurea (n=39,990). The aim of the study
styles – but it will still be individual.
was to compare the risk between therapies of a composite primary outcome of acute myocardial infarction (AMI), stroke
Reference: Aust Fam Physician 2014;43(6):399-402
hosptialisation, or all-cause death. Additional propensity
score matched analysis was performed on a subset of 2436 veterans in the insulin group and 12,180 veterans in the sulphonylurea group. Patients had received metformin for
Impact of changes to reimbursement of fixed combinations
a median of 14 months before treatment intensification;
of inhaled corticosteroids and long-acting β2-agonists in
median follow-up after this addition was 14 months. There were 172 vs 634 events for the primary outcome among
obstructive lung diseases
patients who added insulin vs sulfonylureas, respectively
Authors: Björnsdóttir US et al.
(42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07 to 1.58; p=0.009).
Summary: Outcomes are reported from an evaluation of the effects of a cost-saving policy change introduced by
AMI and stroke rates were statistically similar, 41 vs 229
the Icelandic government in 2010 that limited reimbursement of fixed inhaled corticosteroid/long-acting β2-agonist
events (10.2 and 11.9 events per 1000 person-years; aHR,
(ICS/LABA) combinations. The policy change took effect on 1 January 2010 (index date); data for the year
0.88; 95% CI, 0.59 to 1.30; p=0.52), whereas all-cause
preceding and following this date were analysed in 8241 patients with controlled/partly controlled asthma and/or
death rates were 137 vs 444 events, respectively (33.7 and
chronic obstructive pulmonary disease (COPD) who had been dispensed an ICS/LABA during 2009. Following the
22.7 events per 1000 person-years; aHR, 1.44; 95% CI,
policy change, 47.8% fewer fixed ICS/LABA combinations were dispensed during the post-index period among
1.15 to 1.79; p=0.001). There were 54 vs 258 secondary
patients whose asthma and/or COPD was controlled/partly controlled during the pre-index period. There were also
outcomes: AMI, stroke hospitalisations, or cardiovascular
fewer ICS monocomponents dispensed. After the policy change, 48.6% of patients were no longer receiving any
deaths (22.8 vs 22.5 events per 1000 person-years; aHR,
respiratory medications. This led to reduced disease control, as demonstrated by more healthcare visits (44.0%)
0.98; 95% CI, 0.71 to 1.34; p=0.87).
as well as more oral corticosteroid (76.3%) and short-acting β2-agonist (SABA; 51.2%) dispensations.
Comment: An interesting outcome. From the prescribing figures it seems that there was a significant overall
Comment: I have commented on over 850 papers during
reduction in control of asthma/COPD with reference to the increase in systemic steroid and short-acting
the Research Review series, and (I think) this is the first
bronchodilator prescribing. It is somewhat concerning that nearly 50% of respiratory patients are reported
one in which my interpretation has not been correct. Thank
as receiving no treatment following the policy change. It would be interesting to look further at time off work,
you for the "spotters" emailing about this. On reflection,
hospital admissions, acute presentations, and ED visits. Maybe – just maybe – the savings are expensive in
and reading this paper again – insulin did not win "hands
terms of overall health economics.
down" and the opposite is the case. Beware the sample size as the sulfonylurea set numbers greatly outnumber
Reference: Int J Clin Pract 2014;68(7):812-9
the insulin one, and this is of course reflected in the
absolute numbers of events. In a nutshell there basically was no statistical difference in rate of AMI, stroke, or cardiovascular deaths in the two groups, but all-cause
mortality was markedly increased in those on insulin.
Research Review and you have the right to inspect, update or delete your details at any time.
Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in the process. The reviews are a summarised
interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested
readers review the full trial data before forming a final conclusion on its merits.
Research Review publications are intended for New Zealand health professionals.
For treatment of
Your website password is: PRMELTN
Please review full da Auckland. TAPS PP3836-13MY
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The effect of L-thyroxine substitution on lipid profile, glucose
Effects of changing guidelines
homeostasis, inflammation and coagulation in patients with
on prescribing aspirin
for primary prevention of
Authors: Anagnostis P et al.
Summary: The effects of L-thyroxine therapy on lipidaemic profile, coagulation markers, high-sensitivity C-reactive
Authors: Hissett J et al.
protein (hsCRP) and glucose homoeostasis are reported for 32 patients (mean age 52.1 years) with subclinical
Summary: De-identified electronic health record (EHR)
hypothyroidism. At baseline, mean thyroid-stimulating hormone (TSH) levels were 6.79 mIU/mL. At 6 months, after
data were obtained for 131,050 individuals >17 years
restoration of euthyroidism, significant reductions from baseline were observed in systolic blood pressure (BP; from
of age with a known diagnosis of cardiovascular disease
135.2 to 129.7 mmHg; p=0.03) and diastolic BP (from 79.5 to 72.1 mmHg; p=0.03) only in those patients with
(CVD) or at increased risk of CVD, as determined by
baseline TSH levels >7 mIU/mL. L-thyroxine therapy had no significant effect upon body weight, total cholesterol,
diagnostic, demographic, and clinical data collected
LDL or HDL cholesterol, triglycerides, apolipoprotein B, fasting plasma glucose or insulin, homoeostasis model
from 33 primary care practices in 11 different clinical
assessment-insulin resistance (HOMA-IR), hsCRP, antithrombin III, protein C, protein S, fibrinogen or homocysteine
organisations spread across 6 states in the USA.
levels, except for a decrease in apolipoprotein A1 (p=0.04) and an increase in lipoprotein (a) levels (p=0.02).
Changes in recorded aspirin use were observed among
the patients across 4 time periods (time 1: 1 January
Comment: Subclinical hypothyroidism is not that uncommon. Patients who present with atypical symptoms
2007 to 31 December 2007; time 2: 1 January 2008
often have a thyroid-stimulating hormone test done as part of a screen. If it is high, full thyroid function tests
to 31 December 2008; time 3: 1 January 2009 to
are undertaken (T3 and T4 levels) and the result is that frequently they fall into the "grey" area of being neither
31 May 2010; and time 4: 1 June 2010 to 31 May
one thing nor the other, or perhaps "just within the range of normality". This study suggests that if patients are
2011). From 2007 to 2011, aspirin usage reflected
normotensive then watchful expectancy may be the way to go. If BP is elevated, it may be worthwhile for a trial of
in the EHR increased for the entire population and for
thyroxine replacement to see if this reduces BP.
each individual high-risk diagnosis. The percentage
of the population initiating aspirin therapy for primary
Reference: Int J Clin Pract 2014;68(7):857-63
prevention within a year of diagnosis of CVD risk factors
or CVD "equivalency" increased between 2007 and
2011. Aspirin usage also increased steadily over the
4-year period among those with a new diagnosis of
The value of routine radiography in patients with knee
CVD, indicating no negative impact from new negative
osteoarthritis consulting primary health care: a study of agreement
primary prevention studies.
Authors: Skou ST et al.
Comment: This is yet another study questioning the
Summary: This Danish study explored agreement between the radiographic and clinical diagnosis in knee osteoarthritis
use of aspirin as a prophylactic measure in patients
(OA), as well as the ability of radiography to rule out serious pathology in clinical knee OA. The analysis involved referral
who do not have established CVD. The current
forms from GPs and radiographs of 1334 patients aged >40 years not previously diagnosed with knee OA. A Cohen's
evidence suggests that the risk of adverse effects of
kappa was used to examine the agreement between primary indication for radiographic referral (± clinical knee OA;
aspirin in those without established CVD (including
according to the recommendations from the European League Against Rheumatism) and the radiographic diagnosis
diabetics) is greater than any preventive benefit.
(± radiographic KOA; Kellgren and Lawrence score ≥1). The strength of the agreement was 0.106 to 0.298, with the
Note that this does not apply for established disease.
lowest agreement in the youngest patients and the highest in the oldest patients. An evaluation of radiographic features in a subset of 997 patients with clinical knee OA identified conditions needing further investigation or specific treatment
Reference: J Am Board Fam Med 2014;27(1):78-86
(osteonecrosis, osteochondral lesion, fracture and subluxation) in 5 radiographs (0.5%).
Comment: This is a complex issue involving patient expectation, specialist requirement, allocation of points for
surgery, and as the authors suggest, ruling out other diagnosis or serious pathology. I can only imagine the retort, if I referred a patient to an orthopaedic surgeon for opinion for consideration for joint replacement without an x-ray. But I agree that the film seldom adds to the decision outcome – maybe a need for consideration for radiologists, generalists, and orthopaedic surgeons to rethink.
Reference: Eur J Gen Pract 2014;20(1):10-6
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Independent commentary by Associate Professor Jim Reid.
Jim Reid graduated in medicine at the University of Otago Medical School in Dunedin New Zealand. He had
previously trained as a pharmacist. He undertook his postgraduate work at the University of Miami in Florida.
Currently he is Head of Rural Health and Deputy Dean of the School at the Dunedin School of Medicine. He has a
private family medicine practice at the Caversham Medical Centre, Dunedin, New Zealand.
For full bio .
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Association between melanocytic nevi and
Evidence-based natural health by Dr Chris Tofield
risk of breast diseases: the French E3N
Olive oil intake and risk of cardiovascular
Authors: Kvaskoff M et al.
disease and mortality in the PREDIMED study
Summary: The French E3N study followed 89,902 women aged 40–65 years
Authors: Guasch-Ferré M et al.
from June 1990 to June 2008, exploring associations between number of naevi
Summary: This analysis included 7216 men and women aged 55–80 years
and breast cancer risk. At study entry, women were categorised by number of naevi
participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, assigned
(none; a few; many; very many). During the study period, 5956 breast cancers
at baseline to 1 of 3 interventions: Mediterranean Diets supplemented with nuts or
(including 5245 invasive tumours) were diagnosed. In Cox proportional hazards
extra-virgin olive oil, or a control low-fat diet. None of the participants had CVD at
regression models adjusted for age, education, and known breast cancer risk
enrolment, but they were at high CV risk because of the presence of type 2 diabetes or
factors, women with "very many" naevi had a significantly higher breast cancer risk
≥3 of the following risk factors: current smoking, hypertension, high LDL cholesterol,
(HR 1.13; 95% CI, 1.01 to 1.27 vs "none"; p =0.04), although significance was
low HDL cholesterol, overweight or obesity, and family history of premature CVD
lost after adjustment for personal history of benign breast disease or family history
(stroke, myocardial infarction and CV death). The study aimed to assess the association
of breast cancer. The 10-year absolute risk of invasive breast cancer increased from
between total olive oil intake, its varieties (extra virgin and common olive oil) and
3749 per 100,000 women without naevi to 4124 per 100,000 women with "very
the risk of CVD and mortality. Over a median follow-up of 4.8 years, 277 CV events
many" naevi. The association was restricted to premenopausal women (HR 1.40,
and 323 deaths were recorded. Participants in the highest energy-adjusted tertile of
p =0.01), even after full adjustment (HR 1.34; p =0.03), but did not differ
baseline total olive oil and extra-virgin olive oil consumption had a 35% (HR 0.65; 95%
according to breast cancer type or hormone receptor status. Significantly positive
CI, 0.47 to 0.89) and 39% (HR 0.61; 95% CI, 0.44 to 0.85) lower risk of major CV
dose–response relationships were observed between number of naevi and history
events, respectively, compared to those in the reference. Higher baseline total olive oil
of biopsy-confirmed benign breast disease (n=5169; p <0.0001) and family
consumption was associated with a 48% reduction in the risk of CV mortality (HR 0.52;
history of breast cancer in first-degree relatives (n=7472; p =0.0003).
95% CI, 0.29 to 0.93). Each increase of 10 g/day in extra-virgin olive oil consumption was associated with a 10% reduction in the risk of CV events and a 7% reduction
Comment: Fascinating! The message from this study is that when undertaking
in mortality risk. No significant associations were found for cancer and all-cause
skin checks for naevi, look out for the woman with a large number of naevi.
mortality. The associations between CV events and extra virgin olive oil intake were
The numerical value of "very many" is not evaluated in this study, and of course
significant in the Mediterranean diet intervention groups and not in the control group.
family history etc. is important. But this is an important observation – women with multiple naevi are at greater risk of benign and malignant breast disease.
Comment: Interestingly, the olive oil group in this study did better than the low-fat
diet group. And not only that, but the greater the daily olive oil intake, the lower
Reference: PLoS Med 2014;11(6):e1001660
the CV risk. Should we now be steering our high-risk patients (or anyone else for
that matter) away from the green top milk and recommend more olive oil instead? Food for thought.
Dr Christopher Tofield
Reference: BMC Med 2014;12:78
Dr Tofield completed his medical training at St Bartholomew's
and the Royal London Hospital in London and is now a
fulltime General Practitioner in Tauranga.
For full bio
Effects of ginger for nausea and vomiting in
Authors: Thomson M et al.
Summary: This meta-analysis of randomised, placebo-controlled trials using ginger
for nausea and vomiting in early pregnancy (NVEP) included 6 studies (508 subjects; 256 received ginger and 252 received placebo). Use of ginger ( 1 g daily) for ≥4 days
was found to be associated with a 5-fold likelihood of improvement in NVEP.
Comment: Ginger is a very popular choice for pregnant women suffering from
nausea or vomiting. According to this Canadian meta-analysis, however, you need to ingest approximately 1 g of ginger a day for it to be effective. That's around 8 or 9 Griffins ginger biscuits a day, at 0.12 g ginger per biscuit. Happy munching.
Reference: J Am Board Fam Med 2014;27(1):115-22
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2014 RESEARCH REVIEW
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