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The Big Four Bulletin
6th January 2016 No. 464
Contents
BMJ
No issue published this week.
________________________________________________________________________
JAMA: The Journal of the American Medical Association (5th January 2016)

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen
Consumption and Quality of Life in Obese Older Patients With Heart Failure With
Preserved Ejection Fraction: A Randomized Clinical Trial

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in
Electronic Medical Records

Association Between Use of Oral Fluconazole During Pregnancy and Risk of
Spontaneous Abortion and Stillbirth
 Familial Risk and Heritability of Cancer Among Twins in Nordic Countries
________________________________________________________________________
The Lancet (2nd January 2016)

Safety and performance of the second-generation drug-eluting absorbable metal
scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month
results of a prospective, multicentre, non-randomised, first-in-man trial

Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis
inadequately controlled by topical treatments: a randomised, placebo-controlled, doseranging phase 2b trial

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD):
effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Availability and affordability of cardiovascular disease medicines and their effect on use
in high-income, middle-income, and low-income countries: an analysis of the PURE
study data
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 Current concepts in management of pain in children in the emergency department
________________________________________________________________________
The New England Journal of Medicine (24th December 2015 & 31st December 2015)

Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma

Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection

Selexipag for the Treatment of Pulmonary Arterial Hypertension

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
 A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds
________________________________________________________________________
BMJ
No issue published this week.
Back to Contents
________________________________________________________________________
JAMA: Journal of the American Medical Association (5th January 2016, Vol. 315, No.
1)
Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen
Consumption and Quality of Life in Obese Older Patients With Heart Failure With
Preserved Ejection Fraction: A Randomized Clinical Trial
Dalane W. Kitzman, Peter Brubaker, Timothy Morgan, et al.
JAMA. 2016;315(1):36-46. doi:10.1001/jama.2015.17346
http://jama.jamanetwork.com/article.aspx?articleid=2480484
Abstract
Importance More than 80% of patients with heart failure with preserved ejection fraction
(HFPEF), the most common form of heart failure among older persons, are overweight or
obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major
determinant of reduced quality of life (QOL).
Objective To determine whether caloric restriction (diet) or aerobic exercise training
(exercise) improves exercise capacity and QOL in obese older patients with HFPEF.
Design, Setting, and Participants Randomized, attention-controlled, 2 × 2 factorial trial
conducted from February 2009 through November 2014 in an urban academic medical
center. Of 577 initially screened participants, 100 older obese participants (mean [SD]:
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age, 67 years [5]; body mass index, 39.3 [5.6]) with chronic, stable HFPEF were enrolled
(366 excluded by inclusion and exclusion criteria, 31 for other reasons, and 80 declined
participation).
Interventions Twenty weeks of diet, exercise, or both; attention control consisted of
telephone calls every 2 weeks.
Main Outcomes and Measures Exercise capacity measured as peak oxygen
consumption (VO2, mL/kg/min; co–primary outcome) and QOL measured by the Minnesota
Living with Heart Failure (MLHF) Questionnaire (score range: 0–105, higher scores
indicate worse heart failure–related QOL; co–primary outcome).
Results Of the 100 enrolled participants, 26 participants were randomized to exercise; 24
to diet; 25 to exercise + diet; 25 to control. Of these, 92 participants completed the trial.
Exercise attendance was 84% (SD, 14%) and diet adherence was 99% (SD, 1%). By main
effects analysis, peak VO2 was increased significantly by both interventions: exercise, 1.2
mL/kg body mass/min (95% CI, 0.7 to 1.7), P < .001; diet, 1.3 mL/kg body mass/min (95%
CI, 0.8 to 1.8), P < .001. The combination of exercise + diet was additive (complementary)
for peak VO2 (joint effect, 2.5 mL/kg/min). There was no statistically significant change in
MLHF total score with exercise and with diet (main effect: exercise, −1 unit [95% CI, −8 to
5], P = .70; diet, −6 units [95% CI, −12 to 1], P = .08). The change in peak VO2 was
positively correlated with the change in percent lean body mass (r = 0.32; P = .003) and the
change in thigh muscle:intermuscular fat ratio (r = 0.27; P = .02). There were no studyrelated serious adverse events. Body weight decreased by 7% (7 kg [SD, 1]) in the diet
group, 3% (4 kg [SD, 1]) in the exercise group, 10% (11 kg [SD, 1] in the exercise + diet
group, and 1% (1 kg [SD, 1]) in the control group.
Conclusions and Relevance Among obese older patients with clinically stable HFPEF,
caloric restriction or aerobic exercise training increased peak VO2, and the effects may be
additive. Neither intervention had a significant effect on quality of life as measured by the
MLHF Questionnaire.
Trial Registration clinicaltrials.gov Identifier: NCT00959660
________________________________________________________________________
Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented
in Electronic Medical Records
Sara L. Van Driest, Quinn S. Wells, Sarah Stallings, et al.
JAMA. 2016;315(1):47-57. doi:10.1001/jama.2015.17701
http://jama.jamanetwork.com/article.aspx?articleid=2480485
Abstract
Importance Large-scale DNA sequencing identifies incidental rare variants in established
Mendelian disease genes, but the frequency of related clinical phenotypes in unselected
patient populations is not well established. Phenotype data from electronic medical records
(EMRs) may provide a resource to assess the clinical relevance of rare variants.
Objective To determine the clinical phenotypes from EMRs for individuals with variants
designated as pathogenic by expert review in arrhythmia susceptibility genes.
Design, Setting, and Participants This prospective cohort study included 2022
individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5,
2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network
Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and
KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential
pathogenicity by 3 laboratories with ion channel expertise and by comparison with the
ClinVar database. Relevant phenotypes were determined from EMRs, with data available
from 2002 (or earlier for some sites) through September 10, 2014.
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Exposures One or more variants designated as pathogenic in SCN5A or KCNH2.
Main Outcomes and Measures Arrhythmia or electrocardiographic (ECG) phenotypes
defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG
data, and manual EMR review.
Results Among 2022 study participants (median age, 61 years [interquartile range, 56-65
years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency
<0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were
identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants
were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low
concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was
found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants
(difference, +4%; 95% CI, −5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected
QT intervals were not different in variant carriers vs those without (median, 429 vs 439
milliseconds; difference, −10 milliseconds; 95% CI, −16 to +3 milliseconds; P = .17). After
manual review, 22 of 63 participants (35%) with designated variants had any ECG or
arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds.
Conclusions and Relevance Among laboratories experienced in genetic testing for
cardiac arrhythmia disorders, there was low concordance in designating SCN5A and
KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic
genetic variants were not associated with an abnormal phenotype. These findings raise
questions about the implications of notifying patients of incidental genetic findings.
________________________________________________________________________
Association Between Use of Oral Fluconazole During Pregnancy and Risk of
Spontaneous Abortion and Stillbirth
Ditte Mølgaard-Nielsen, Henrik Svanström, Mads Melbye, Anders Hviid, Björn Pasternak
JAMA. 2016;315(1):58-67. doi:10.1001/jama.2015.17844.
http://jama.jamanetwork.com/article.aspx?articleid=2480487
Abstract
Importance Vaginal candidiasis is common during pregnancy. Although intravaginal
formulations of topical azole antifungals are first-line treatment for pregnant women, oral
fluconazole is often used despite limited safety information.
Objective To study the association between oral fluconazole exposure during pregnancy
and the risk of spontaneous abortion and stillbirth.
Design, Setting, and Participants Nationwide register-based cohort study in Denmark,
1997-2013. From a cohort of 1 405 663 pregnancies, oral fluconazole–exposed
pregnancies were compared with up to 4 unexposed pregnancies matched on propensity
score, maternal age, calendar year, and gestational age (based on gestational age at first
day of treatment with eligible controls surviving through this date). To test for confounding
by indication, pregnancies exposed to intravaginal formulations of topical azoles were
used as an additional comparator group.
Exposures Filled prescriptions for oral fluconazole were obtained from the National
Prescription Register.
Main Outcomes and Measures Hazard ratios (HRs) for spontaneous abortion and
stillbirth, estimated using proportional hazards regression.
Results Among 3315 women exposed to oral fluconazole from 7 through 22 weeks’
gestation, 147 experienced a spontaneous abortion, compared with 563 among 13 246
unexposed matched women. There was a significantly increased risk of spontaneous
abortion associated with fluconazole exposure (HR, 1.48; 95% CI, 1.23-1.77). Among
5382 women exposed to fluconazole from gestational week 7 to birth, 21 experienced a
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stillbirth, compared with 77 among 21 506 unexposed matched women. There was no
significant association between fluconazole exposure and stillbirth (HR, 1.32 [95% CI,
0.82-2.14]). Using topical azole exposure as the comparison, 130 of 2823 women exposed
to fluconazole vs 118 of 2823 exposed to topical azoles had a spontaneous abortion (HR,
1.62 [95% CI, 1.26-2.07]); 20 of 4301 women exposed to fluconazole vs 22 of 4301
exposed to topical azoles had a stillbirth (HR, 1.18 [95% CI, 0.64-2.16]).
Conclusions and Relevance In this nationwide cohort study in Denmark, use of oral
fluconazole in pregnancy was associated with a statistically significant increased risk of
spontaneous abortion compared with risk among unexposed women and women with
topical azole exposure in pregnancy. Until more data on the association are available,
cautious prescribing of fluconazole in pregnancy may be advisable. Although the risk of
stillbirth was not significantly increased, this outcome should be investigated further.
________________________________________________________________________
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries
Lorelei A. Mucci, Jacob B. Hjelmborg, Jennifer R. Harris, et al.
JAMA. 2016;315(1):68-76. doi:10.1001/jama.2015.17703.
http://jama.jamanetwork.com/article.aspx?articleid=2480486
Abstract
Importance Estimates of familial cancer risk from population-based studies are essential
components of cancer risk prediction.
Objective To estimate familial risk and heritability of cancer types in a large twin cohort.
Design, Setting, and Participants Prospective study of 80 309 monozygotic and 123 382
same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of
Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years
between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804
who emigrated and were lost to follow-up.
Exposures Shared environmental and heritable risk factors among pairs of twins.
Main Outcomes and Measures The main outcome was incident cancer. Time-to-event
analyses were used to estimate familial risk (risk of cancer in an individual given a twin’s
development of cancer) and heritability (proportion of variance in cancer risk due to
interindividual genetic differences) with follow-up via cancer registries. Statistical models
adjusted for age and follow-up time, and accounted for censoring and competing risk of
death.
Results A total of 27 156 incident cancers were diagnosed in 23 980 individuals,
translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among
1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these,
38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer
type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer,
with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in
dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in
monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared
with the cumulative risk in the overall cohort (32%). For most cancer types, there were
significant familial risks and the cumulative risks were higher in monozygotic than dizygotic
twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability
was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate
(57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%;
95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%),
and corpus uteri (27%; 95% CI, 11%-43%).
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Conclusions and Relevance In this long-term follow-up study among Nordic twins, there
was significant excess familial risk for cancer overall and for specific types of cancer,
including prostate, melanoma, breast, ovary, and uterus. This information about hereditary
risks of cancers may be helpful in patient education and cancer risk counseling.
Back to Contents
________________________________________________________________________
The Lancet (2nd January 2016, Vol. 387, No. 10013)
Safety and performance of the second-generation drug-eluting absorbable metal
scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month
results of a prospective, multicentre, non-randomised, first-in-man trial
Michael Haude, Hüseyin Ince, Alexandre Abizaid, et al.
The Lancet Volume 387, No. 10013, p31–39, 2 January 2016
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00447-X/abstract
Summary
Background
Absorbable scaffolds were designed to overcome the limitations of conventional, nonabsorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds
are commercially available. We aimed to assess the safety and performance of a novel
second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with
de-novo coronary artery lesions.
Methods
We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous
coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain,
Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or
documented silent ischaemia, and a maximum of two de-novo lesions with a reference
vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months
1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and
a subgroup of patients was scheduled for intravascular ultrasound, optical coherence
tomography, and vasomotion assessment. All patients were recommended to take dual
antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late
lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with
ClinicalTrials.gov, number NCT01960504.
Findings
Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary
target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37),
and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients.
Intravascular ultrasound assessments showed a preservation of the scaffold area (mean
6·24 mm2 [SD 1·15] post-procedure vs 6·21 mm2 [1·22] at 6 months) with a low mean
neointimal area (0·08 mm2 [0·09]), and optical coherence tomography did not detect any
intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient
died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and
two (2%) patients needed clinically driven target lesion revascularisation. No definite or
probable scaffold thrombosis was observed.
Interpretation
Our findings show that implantation of the DREAMS 2G device in de-novo coronary
lesions is feasible, with favourable safety and performance outcomes at 6 months. This
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novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds
for treatment of obstructive coronary disease.
Funding
Biotronik AG.
________________________________________________________________________
Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis
inadequately controlled by topical treatments: a randomised, placebo-controlled,
dose-ranging phase 2b trial
Diamant Thaçi, Eric L Simpson, Lisa A Beck, et al.
The Lancet Volume 387, No. 10013, p40–52, 2 January 2016
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00388-8/abstract
Summary
Background
Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite
drivers of atopic dermatitis, evidenced by marked improvement after treatment with
dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to
assess the efficacy and safety of several dose regimens of dupilumab in adults with
moderate-to-severe atopic dermatitis inadequately controlled by topical treatments.
Methods
In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18
years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher
at screening (≥16 at baseline) and inadequate response to topical treatments from 91
study centres, including hospitals, clinics, and academic institutions, in Canada, Czech
Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly
assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by
Investigator's Global Assessment) and region (Japan vs rest of world) to receive
subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2
weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16
weeks. We used a central randomisation scheme, provided by an interactive voice
response system. Drug kits were coded, providing masking to treatment assignment, and
allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks
received volume-matched placebo every week when dupilumab was not given to ensure
double blinding. The primary outcome was efficacy of dupilumab dose regimens based on
EASI score least-squares mean percentage change (SE) from baseline to week 16.
Analyses included all randomly assigned patients who received one or more doses of
study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988.
Findings
Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and
380 patients were randomly assigned. 379 patients received one or more doses of study
drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks
[n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]).
EASI score improvements favoured all dupilumab regimens versus placebo (p<0·0001):
300 mg once a week (−74% [SE 5·16]), 300 mg every 2 weeks (−68% [5·12]), 200 mg
every 2 weeks (−65% [5·19]), 300 mg every 4 weeks (−64% [4·94]), 100 mg every 4
weeks (−45% [4·99]); placebo (−18% [5·20]). 258 (81%) of 318 patients given dupilumab
and 49 (80%) of 61 patients given placebo reported treatment-emergent adverse events;
nasopharyngitis was the most frequent (28% and 26%, respectively).
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Interpretation
Dupilumab improved clinical responses in adults with moderate-to-severe atopic dermatitis
in a dose-dependent manner, without significant safety concerns. Our findings show that
IL-4 and IL-13 are key drivers of atopic dermatitis.
Funding
Sanofi and Regeneron Pharmaceuticals.
________________________________________________________________________
Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD):
effectiveness results from the pilot phase of a pragmatic open-label randomised
trial
Sheena McCormack, David T Dunn, Monica Desai, et al.
The Lancet Volume 387, No. 10013, p53–60, 2 January 2016
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00056-2/abstract
Summary
Background
Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis
(PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit
could be counteracted by risk compensation in users of PrEP. We did the PROUD study to
assess this effect.
Methods
PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We
enrolled HIV-negative gay and other men who have sex with men who had had anal
intercourse without a condom in the previous 90 days. Participants were randomly
assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and
emtricitabine (200 mg) either immediately or after a deferral period of 1 year.
Randomisation was done via web-based access to a central computer-generated list with
variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary
outcomes for the pilot phase were time to accrue 500 participants and retention;
secondary outcomes included incident HIV infection during the deferral period, safety,
adherence, and risk compensation. The trial is registered with ISRCTN (number
ISRCTN94465371) and ClinicalTrials.gov (NCT02065986).
Findings
We enrolled 544 participants (275 in the immediate group, 269 in the deferred group)
between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the
trial steering committee recommended on Oct 13, 2014, that all deferred participants be
offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patientyears in the immediate group versus 222 (90%) of 245 patient-years in the deferred group.
Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in
the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure
prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001;
absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a
similar population would need access to 1 year of PrEP to avert one HIV infection. We
recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea,
headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the
occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia,
between groups, despite a suggestion of risk compensation among some PrEP recipients.
Interpretation
In this high incidence population, daily tenofovir–emtricitabine conferred even higher
protection against HIV than in placebo-controlled trials, refuting concerns that
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effectiveness would be less in a real-world setting. There was no evidence of an increase
in other sexually transmitted infections. Our findings strongly support the addition of PrEP
to the standard of prevention for men who have sex with men at risk of HIV infection.
Funding
MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.
________________________________________________________________________
Availability and affordability of cardiovascular disease medicines and their effect on
use in high-income, middle-income, and low-income countries: an analysis of the
PURE study data
Rasha Khatib, Martin McKee, Harry Shannon, et al. for the PURE study investigators
The Lancet Volume 387, No. 10013, p61–69, 2 January 2016
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00469-9/abstract
Summary
Background
WHO has targeted that medicines to prevent recurrent cardiovascular disease be available
in 80% of communities and used by 50% of eligible individuals by 2025. We have
previously reported that use of these medicines is very low, but now aim to assess how
such low use relates to their lack of availability or poor affordability.
Methods
We analysed information about availability and costs of cardiovascular disease medicines
(aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies
gathered from 596 communities in 18 countries participating in the Prospective Urban
Rural Epidemiology (PURE) study. Medicines were considered available if present at the
pharmacy when surveyed, and affordable if their combined cost was less than 20% of
household capacity-to-pay. We compared results from high-income, upper middle-income,
lower middle-income, and low-income countries. Data from India were presented
separately given its large, generic pharmaceutical industry.
Findings
Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four
cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of
30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59
rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%)
of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and
one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%)
of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular
disease medicines were potentially unaffordable for 0·14% of households in high-income
countries (14 of 9934 households), 25% of upper middle-income countries (6299 of
24 776), 33% of lower middle-income countries (13 253 of 40 023), 60% of low-income
countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16 874).
In low-income and middle-income countries, patients with previous cardiovascular disease
were less likely to use all four medicines if fewer than four were available (odds ratio [OR]
0·16, 95% CI 0·04–0·57). In communities in which all four medicines were available,
patients were less likely to use medicines if the household potentially could not afford them
(0·16, 0·04–0·55).
Interpretation
Secondary prevention medicines are unavailable and unaffordable for a large proportion of
communities and households in upper middle-income, lower middle-income, and lowincome countries, which have very low use of these medicines. Improvements to the
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availability and affordability of key medicines is likely to enhance their use and help
towards achieving WHO's targets of 50% use of key medicines by 2025.
Funding
Population Health Research Institute, the Canadian Institutes of Health Research, Heart
and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and
Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline,
Novartis, King Pharma, and national or local organisations in participating countries.
________________________________________________________________________
Review
Current concepts in management of pain in children in the emergency department
Baruch S Krauss, Lorenzo Calligaris, Steven M Green, Egidio Barbi
The Lancet Volume 387, No. 10013, p83–92, 2 January 2016
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61686-X/abstract
Summary
Pain is common in children presenting to emergency departments with episodic illnesses,
acute injuries, and exacerbation of chronic disorders. We review recognition and
assessment of pain in infants and children and discuss the manifestations of pain in
children with chronic illness, recurrent pain syndromes, and cognitive impairment,
including the difficulties of pain management in these patients. Non-pharmacological
interventions, as adjuncts to pharmacological management for acute anxiety and pain, are
described by age and development. We discuss the pharmacological management of
acute pain and anxiety, reviewing invasive and non-invasive routes of administration,
pharmacology, and adverse effects.
Back to Contents
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The New England Journal of Medicine (24th December 2015 Vol. 373, No. 26 & 31st
December 2015, Vol. 373, No. 27)
Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma
Michael Schaapveld, Berthe M.P. Aleman, Anna M. van Eggermond et al.
N Engl J Med 2015; 373:2499-2511 December 24, 2015 DOI: 10.1056/NEJMoa1505949
http://www.nejm.org/doi/full/10.1056/NEJMoa1505949
Abstract
BACKGROUND
Survivors of Hodgkin’s lymphoma are at increased risk for treatment-related subsequent
malignant neoplasms. The effect of less toxic treatments, introduced in the late 1980s, on
the long-term risk of a second cancer remains unknown.
METHODS
We enrolled 3905 persons in the Netherlands who had survived for at least 5 years after
the initiation of treatment for Hodgkin’s lymphoma. Patients had received treatment
between 1965 and 2000, when they were 15 to 50 years of age. We compared the risk of
a second cancer among these patients with the risk that was expected on the basis of
cancer incidence in the general population. Treatment-specific risks were compared within
the cohort.
RESULTS
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With a median follow-up of 19.1 years, 1055 second cancers were diagnosed in 908
patients, resulting in a standardized incidence ratio (SIR) of 4.6 (95% confidence interval
[CI], 4.3 to 4.9) in the study cohort as compared with the general population. The risk was
still elevated 35 years or more after treatment (SIR, 3.9; 95% CI, 2.8 to 5.4), and the
cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95%
CI, 45.4 to 51.5). The cumulative incidence of second solid cancers did not differ according
to study period (1965–1976, 1977–1988, or 1989–2000) (P=0.71 for heterogeneity).
Although the risk of breast cancer was lower among patients who were treated with
supradiaphragmatic-field radiotherapy not including the axilla than among those who were
exposed to mantle-field irradiation (hazard ratio, 0.37; 95% CI, 0.19 to 0.72), the risk of
breast cancer was not lower among patients treated in the 1989–2000 study period than
among those treated in the two earlier periods. A cumulative procarbazine dose of 4.3 g or
more per square meter of body-surface area (which has been associated with premature
menopause) was associated with a significantly lower risk of breast cancer (hazard ratio
for the comparison with no chemotherapy, 0.57; 95% CI, 0.39 to 0.84) but a higher risk of
gastrointestinal cancer (hazard ratio, 2.70; 95% CI, 1.69 to 4.30).
CONCLUSIONS
The risk of second solid cancers did not appear to be lower among patients treated in the
most recent calendar period studied (1989–2000) than among those treated in earlier
periods. The awareness of an increased risk of second cancer remains crucial for
survivors of Hodgkin’s lymphoma. (Funded by the Dutch Cancer Society).
________________________________________________________________________
Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection
William M. Geisler, Apurva Uniyal, Jeannette Y. Lee, et al.
N Engl J Med 2015; 373:2512-2521 December 24, 2015 DOI: 10.1056/NEJMoa1502599
http://www.nejm.org/doi/full/10.1056/NEJMoa1502599
Abstract
BACKGROUND
Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial
reproductive morbidity. Recent studies have raised concern about the efficacy of
azithromycin for the treatment of chlamydia infection.
METHODS
We conducted a randomized trial comparing oral azithromycin with doxycycline for the
treatment of urogenital chlamydia infection among adolescents in youth correctional
facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline
(100 mg twice daily for 7 days). The treatment was directly observed. The primary end
point was treatment failure at 28 days after treatment initiation, with treatment failure
determined on the basis of nucleic acid amplification testing, sexual history, and outer
membrane protein A (OmpA) genotyping of C. trachomatis strains.
RESULTS
Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin,
and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each
treatment group (65% male) made up the per-protocol population. There were no
treatment failures in the doxycycline group. In the azithromycin group, treatment failure
occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed
difference in failure rates between the treatment groups was 3.2 percentage points, with
an upper boundary of the 90% confidence interval of 5.9 percentage points, which
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exceeded the prespecified absolute 5-percentage-point cutoff for establishing the
noninferiority of azithromycin.
CONCLUSIONS
In the context of a closed population receiving directly observed treatment for urogenital
chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline
was 100%. The noninferiority of azithromycin was not established in this setting. (Funded
by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number,
NCT00980148).
________________________________________________________________________
Selexipag for the Treatment of Pulmonary Arterial Hypertension
Olivier Sitbon, Richard Channick, Kelly M. Chin, et al. for the GRIPHON Investigators
N Engl J Med 2015; 373:2522-2533 December 24, 2015 DOI: 10.1056/NEJMoa1503184
http://www.nejm.org/doi/full/10.1056/nejmoa1503184
Abstract
BACKGROUND
In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown
to be beneficial in the treatment of pulmonary arterial hypertension.
METHODS
In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we
randomly assigned 1156 patients with pulmonary arterial hypertension to receive placebo
or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were
eligible for enrollment if they were not receiving treatment for pulmonary arterial
hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist,
a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of
death from any cause or a complication related to pulmonary arterial hypertension up to
the end of the treatment period (defined for each patient as 7 days after the date of the last
intake of selexipag or placebo).
RESULTS
A primary end-point event occurred in 397 patients — 41.6% of those in the placebo group
and 27.0% of those in the selexipag group (hazard ratio in the selexipag group as
compared with the placebo group, 0.60; 99% confidence interval, 0.46 to 0.78; P<0.001).
Disease progression and hospitalization accounted for 81.9% of the events. The effect of
selexipag with respect to the primary end point was similar in the subgroup of patients who
were not receiving treatment for the disease at baseline and in the subgroup of patients
who were already receiving treatment at baseline (including those who were receiving a
combination of two therapies). By the end of the study, 105 patients in the placebo group
and 100 patients in the selexipag group had died from any cause. Overall, 7.1% of patients
in the placebo group and 14.3% of patients in the selexipag group discontinued their
assigned regimen prematurely because of adverse events. The most common adverse
events in the selexipag group were consistent with the known side effects of prostacyclin,
including headache, diarrhea, nausea, and jaw pain.
CONCLUSIONS
Among patients with pulmonary arterial hypertension, the risk of the primary composite
end point of death or a complication related to pulmonary arterial hypertension was
significantly lower with selexipag than with placebo. There was no significant difference in
mortality between the two study groups. (Funded by Actelion Pharmaceuticals; GRIPHON
ClinicalTrials.gov number, NCT01106014).
________________________________________________________________________
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Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
Dominique Baeten, Joachim Sieper, Jürgen Braun, et al. for the MEASURE 1 and
MEASURE 2 Study Groups
N Engl J Med 2015; 373:2534-2548 December 24, 2015 DOI: 10.1056/NEJMoa1505066
http://www.nejm.org/doi/full/10.1056/nejmoa1505066
Abstract
BACKGROUND
Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to
control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase
3 trials of secukinumab in patients with active ankylosing spondylitis.
METHODS
In two double-blind trials, we randomly assigned patients to receive secukinumab or
placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg
per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by
subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks
starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous
secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3;
and every 4 weeks starting at week 4. At week 16, patients in the placebo group were
randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The
primary end point was the proportion of patients with at least 20% improvement in
Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week
16.
RESULTS
In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for
subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively
(P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%,
and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo,
respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The
significant improvements were sustained through 52 weeks. Infections, including
candidiasis, were more common with secukinumab than with placebo during the placebocontrolled period of MEASURE 1. During the entire treatment period, pooled exposureadjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s
disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumabtreated patients.
CONCLUSIONS
Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous
loading, provided significant reductions in the signs and symptoms of ankylosing
spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in
significant improvement only with a higher intravenous loading dose. (Funded by Novartis
Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375).
________________________________________________________________________
Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection
Jordan J. Feld, Ira M. Jacobson, Christophe Hézode, et al for the ASTRAL-1 Investigators
N Engl J Med 2015; 373:2599-2607 December 31, 2015 DOI: 10.1056/NEJMoa1512610
http://www.nejm.org/doi/full/10.1056/NEJMoa1512610
Abstract
BACKGROUND
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A simple treatment regimen that is effective in a broad range of patients who are
chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.
METHODS
We conducted a phase 3, double-blind, placebo-controlled study involving untreated and
previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including
those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly
assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the
NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching
placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions,
patients with genotype 5 did not undergo randomization but were assigned to the
sofosbuvir–velpatasvir group. The primary end point was a sustained virologic response at
12 weeks after the end of therapy.
RESULTS
Of the 624 patients who received treatment with sofosbuvir–velpatasvir, 34% had HCV
genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and
7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had
been previously treated for HCV. The rate of sustained virologic response among patients
receiving sofosbuvir–velpatasvir was 99% (95% confidence interval, 98 to >99). Two
patients receiving sofosbuvir–velpatasvir, both with HCV genotype 1, had a virologic
relapse. None of the 116 patients receiving placebo had a sustained virologic response.
Serious adverse events were reported in 15 patients (2%) in the sofosbuvir–velpatasvir
group and none in the placebo group.
CONCLUSIONS
Once-daily sofosbuvir–velpatasvir for 12 weeks provided high rates of sustained virologic
response among both previously treated and untreated patients infected with HCV
genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead
Sciences; ClinicalTrials.gov number, NCT02201940).
________________________________________________________________________
Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Graham R. Foster, Nezam Afdhal, Stuart K. Roberts, et al. for the ASTRAL-2 and
ASTRAL-3 Investigators
N Engl J Med 2015; 373:2608-2617 December 31, 2015 DOI: 10.1056/NEJMoa1512612
http://www.nejm.org/doi/full/10.1056/NEJMoa1512612
Abstract
BACKGROUND
In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor
sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic
response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.
METHODS
We conducted two randomized, phase 3, open-label studies involving patients who had
received previous treatment for HCV genotype 2 or 3 and those who had not received
such treatment, including patients with compensated cirrhosis. In one trial, patients with
HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir,
in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weightbased ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype
3 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir for 12 weeks
(277 patients) or sofosbuvir–ribavirin for 24 weeks (275 patients). The primary end point
for the two trials was a sustained virologic response at 12 weeks after the end of therapy.
RESULTS
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Among patients with HCV genotype 2, the rate of sustained virologic response in the
sofosbuvir–velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which
was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir–ribavirin group
(P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in
the sofosbuvir–velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the
rate of 80% (95% CI, 75 to 85) in the sofosbuvir–ribavirin group (P<0.001). The most
common adverse events in the two studies were fatigue, headache, nausea, and
insomnia.
CONCLUSIONS
Among patients with HCV genotype 2 or 3 with or without previous treatment, including
those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir–velpatasvir
resulted in rates of sustained virologic response that were superior to those with standard
treatment with sofosbuvir–ribavirin. (Funded by Gilead Sciences; ASTRAL-2
ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953).
________________________________________________________________________
Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
Michael P. Curry, Jacqueline G. O’Leary, Natalie Bzowej, et al. for the ASTRAL-4
Investigators
N Engl J Med 2015; 373:2618-2628 December 31, 2015 DOI: 10.1056/NEJMoa1512614
http://www.nejm.org/doi/full/10.1056/NEJMoa1512614
Abstract
BACKGROUND
As the population that is infected with the hepatitis C virus (HCV) ages, the number of
patients with decompensated cirrhosis is expected to increase.
METHODS
We conducted a phase 3, open-label study involving both previously treated and
previously untreated patients infected with HCV genotypes 1 through 6 who had
decompensated cirrhosis (classified as Child–Pugh–Turcotte class B). Patients were
randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor
sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks,
sofosbuvir–velpatasvir plus ribavirin for 12 weeks, or sofosbuvir–velpatasvir for 24 weeks.
The primary end point was a sustained virologic response at 12 weeks after the end of
therapy.
RESULTS
Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2,
15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype
5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI],
74 to 90) among patients who received 12 weeks of sofosbuvir–velpatasvir, 94% (95% CI,
87 to 98) among those who received 12 weeks of sofosbuvir–velpatasvir plus ribavirin, and
86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir–velpatasvir.
Post hoc analysis did not detect any significant differences in rates of sustained virologic
response among the three study groups. Serious adverse events occurred in 19% of
patients who received 12 weeks of sofosbuvir–velpatasvir, 16% of those who received 12
weeks of sofosbuvir–velpatasvir plus ribavirin, and 18% of those who received 24 weeks of
sofosbuvir–velpatasvir. The most common adverse events were fatigue (29%), nausea
(23%), and headache (22%) in all patients and anemia (31%) in the patients receiving
ribavirin.
CONCLUSIONS
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Treatment with sofosbuvir–velpatasvir with or without ribavirin for 12 weeks and with
sofosbuvir–velpatasvir for 24 weeks resulted in high rates of sustained virologic response
in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences;
ASTRAL-4 ClinicalTrials.gov number, NCT02201901).
________________________________________________________________________
A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds
The FLOW Investigators
N Engl J Med 2015; 373:2629-2641December 31, 2015 DOI: 10.1056/NEJMoa1508502
http://www.nejm.org/doi/full/10.1056/nejmoa1508502
Abstract
BACKGROUND
The management of open fractures requires wound irrigation and débridement to remove
contaminants, but the effectiveness of various pressures and solutions for irrigation
remains controversial. We investigated the effects of castile soap versus normal saline
irrigation delivered by means of high, low, or very low irrigation pressure.
METHODS
In this study with a 2-by-3 factorial design, conducted at 41 clinical centers, we randomly
assigned patients who had an open fracture of an extremity to undergo irrigation with one
of three irrigation pressures (high pressure [>20 psi], low pressure [5 to 10 psi], or very low
pressure [1 to 2 psi]) and one of two irrigation solutions (castile soap or normal saline).
The primary end point was reoperation within 12 months after the index surgery for
promotion of wound or bone healing or treatment of a wound infection.
RESULTS
A total of 2551 patients underwent randomization, of whom 2447 were deemed eligible
and included in the final analyses. Reoperation occurred in 109 of 826 patients (13.2%) in
the high-pressure group, 103 of 809 (12.7%) in the low-pressure group, and 111 of 812
(13.7%) in the very-low-pressure group. Hazard ratios for the three pairwise comparisons
were as follows: for low versus high pressure, 0.92 (95% confidence interval [CI], 0.70 to
1.20; P=0.53), for high versus very low pressure, 1.02 (95% CI, 0.78 to 1.33; P=0.89), and
for low versus very low pressure, 0.93 (95% CI, 0.71 to 1.23; P=0.62). Reoperation
occurred in 182 of 1229 patients (14.8%) in the soap group and in 141 of 1218 (11.6%) in
the saline group (hazard ratio, 1.32, 95% CI, 1.06 to 1.66; P=0.01).
CONCLUSIONS
The rates of reoperation were similar regardless of irrigation pressure, a finding that
indicates that very low pressure is an acceptable, low-cost alternative for the irrigation of
open fractures. The reoperation rate was higher in the soap group than in the saline group.
(Funded by the Canadian Institutes of Health Research and others; FLOW
ClinicalTrials.gov number, NCT00788398).
Back to Contents
________________________________________________________________________
Sources
BMJ: British Medical Journal
http://www.bmj.com/theBMJ
JAMA: The Journal of the American Medical
Association
http://jama.ama-assn.org/
- 16 -
The Lancet
www.thelancet.com
The New England Journal of Medicine
The British Medical Journal (BMJ), The Lancet and the
New England Journal of Medicine (NEJM) can all be
accessed in full-text through your NHS Athens
account. The Journal of the American Medical
Association (JAMA) is available in print only. Print
copies are held in the Library.
http://content.nejm.org/
https://www.evidence.nhs.uk/n
hs-evidence-content/journalsand-databases
If you have not already registered for an NHS Athens
Account, please register at:
or http://www.openathens.net/
https://openathens.nice.org.uk
/
NB: It is recommended that you register on a Trust
(NHS) PC for speedy confirmation of your username
and password. Once registered, your account can be
accessed from any device with online access.
________________________________________________________________________
Library News
________________________________________________________________________
DynaMed Plus
Good news! Following a successful trial of this resource, the Library & Knowledge Service
has purchased a 12 month subscription. DynaMed Plus is the enhanced version of
DynaMed and comprises a more user-friendly search feature along with a range of
different images.
DynaMed Plus can be accessed via the Library intranet and internet pages. To log in you
will need an Athens username & password (there is a hyperlink to register for an account
on the Library intranet homepage).
Many thanks to all those who took part in the trial and responded to the survey.
________________________________________________________________________
Free Exam Resources for Doctors
Please find below links to resources providing free, or partially free, access to exam
resources for doctors:
MRCPass: https://www.mrcpass.com
Revise MRCP: http://www.revisemrcp.com/
- 17 -
Medexam.net: http://www.medexam.net/
Almost a Doctor: http://almostadoctor.co.uk/
PassMed: http://www.passmed.co.uk/
Radiology Master-Class: http://radiologymasterclass.co.uk
________________________________________________________________________
Health Service Journal
The Library has had an online subscription to the ‘Health Service Journal’ from
January 2015. We are aware that a number of Trust staff have registered for the
online access but unfortunately due to the high cost of the renewal, the online
subscription will cease on 31st December 2015.
The Library has a subscription to the print version for 2016. If you require any
articles from this journal, please contact the Library.
________________________________________________________________________
Have you heard of PROSPERO?
PROSPERO is the International Prospective Register of Systematic Reviews
produced by the Centre for Reviews and Dissemination (CRD) at the University of York.
PROSPERO is helping to reduce unplanned duplication and encouraging greater
information sharing and collaboration worldwide. Registration increases transparency and
helps safeguard against selective reporting; allowing readers to compare published
research with what was planned at the outset. The database now holds over 10,000
published records.
Overview of PROSPERO: http://www.crd.york.ac.uk/PROSPERO/
Link to PROSPERO database: http://www.crd.york.ac.uk/prospero/search.asp
________________________________________________________________________
Library Training Sessions 2016
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Critical appraisal - an introduction:
¨ February Tuesday 2nd 2:00pm – 3:30pm (RCT paper), Thursday 25th 2:00pm – 3:30pm
(Qualitative Study paper)
¨ March Tuesday 1st 10:30am – 12:00pm (RCT paper), Thursday 17th 2:00pm – 3:30pm
(Systematic Review paper)
¨ April Tuesday 5th 2:00pm – 3:30pm (Qualitative Study paper), Thursday 14th 10:30am –
12:00pm (RCT paper)
¨ May Wednesday 4th 2:00pm – 3:30pm (Systematic Review paper), Tuesday 17th
10:30am – 12:00pm (RCT paper)
¨ June Thursday 2nd 10:30am –12:00pm (Qualitative Study paper), Tuesday 21st 2:00pm
– 3:30pm (RCT paper)
RCT research - study design basics & critical appraisal (joint session
with Trust statisticians):
¨ February Friday 26th 10:30am – 12pm
Includes practical critical appraisal session
¨ June Wednesday 15th 10:30am – 12pm
Includes practical critical appraisal session
Booking Training
To book a place on any of the above courses please contact Suzanne Toft, Training
Librarian (Chartered), on extension 88148 or via email at [email protected].
________________________________________________________________________
Produced by:
Library & Knowledge Service
Derby Teaching Hospitals NHS Foundation Trust
Contact:
[email protected]
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Follow us on Twitter @DHFTLibrary
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