BMJ | 17 april 2010 | VoluMe 340 861
For the full versions of these articles see bmj.com
of diagnoses that account for 80% of all deaths in hospitals
nationally.3 A figure of 100 is the national reference value
and hospitals with higher or lower adjusted mortality have
values above or below 100.
The North West London Hospitals NHS Trust serves a
population of about 500 000. The trust received adverse
media coverage following the Healthcare Commission’s
report on its maternity services in July 20054 and in March
and April 20065 regarding a drug trial at Northwick Park
Hospital in which six men developed organ failure. Both
stories had an impact on staff morale and on patients’ per-
ceptions of Northwick Park Hospital. The HSMR for the
trust for 2006-7 was 84.6, 15.4 points below the national
value. We initiated a scheme aimed at reducing mortality
rates and increasing public confidence in the quality of
In 2006-7 there were 1142 deaths in North West London
Hospitals NHS Trust within the diagnoses used to calculate
the HSMR. We set a goal of a reduction of 110 deaths in
2007-8, equivalent to an HSMR of 81.0.
We targeted the diagnoses responsible for the largest
number of deaths for which evidence based methods to
reduce death rates were available. For two of these areas
we used Institute for Healthcare Improvement’s “care
bundles.”6 Care bundles are checklists of accepted clinical
guidelines. The institute defines a care bundle as “a col-
lection of processes needed to effectively and safely care
for patients undergoing particular treatments with inher-
ent risks. Several interventions are ‘bundled’ together
and, when combined, significantly improve patient care
For the six other treatment areas, the clinical elements
of the bundles were agreed by consensus with clinicians,
based on UK and US clinical guidelines.7-10 The format of
the bundles comprised a medical notes component, a flag
to mark the patients involved, and a tracer backing form
(see bmj.com). Clinicians were trained and encouraged to
use the bundles.
The top 25 diagnoses in the Clinical Classification Sys-
tem11 that in 2006-7 led to the largest number of deaths in
the trust were targeted using the eight care bundles (box
1). The 13 diagnoses that were monitored as best covering
the eight care bundles—the targeted diagnoses—are shown
in box 2.
Quality iMProveMent rePort
using care bundles to reduce in-hospital mortality:
Elizabeth Robb,1 2 Brian Jarman,3 4 Ganesh Suntharalingam,1 Clare Higgens,1 Rachel Tennant,1 Karen Elcock5
1North West London Hospitals NHS
Trust, Harrow HA1 3UJ
2Nursing, London South Bank
University, London SE1 0AA
3Imperial College, London
4Institute for Healthcare
Improvement, Cambridge, MA
5Thames Valley University, Slough
Correspondence to: B Jarman
Cite this as: BMJ 2010;340:c1234
Problem To reduce hospital inpatient mortality and thus
increase public confidence in the quality of patient care
in an urban acute hospital trust after adverse media
Design Eight care bundles of treatments known to be
effective in reducing in-hospital mortality were used in
the intervention year; adjusted mortality (from hospital
episode statistics) was compared to the preceding year
for the 13 diagnoses targeted by the intervention care
bundles, 43 non-targeted diagnoses, and overall mortality
for the 56 hospital standardised mortality ratio (HSMR)
diagnoses covering 80% of hospital deaths.
Setting Acute hospital trust in north west London.
Strategies for change Use of clinical guidelines in care
bundles in eight targeted clinical areas.
Interventions Use of care bundles in treatment areas for the
diagnoses leading to most deaths in the trust in 2006-7.
Key measures for improvement Change in adjusted
mortality in targeted and non-targeted diagnostic groups;
hospital standardised mortality ratio (HSMR) during the
intervention year compared with the preceding year.
Effect of the change The standardised mortality ratio (SMR)
of the targeted diagnoses and the HSMR both showed
significant reductions, and the non-targeted diagnoses
showed a slight reduction. Cumulative sum charts showed
significant reductions of SMRs in 11 of the 13 diagnoses
targeted in the year of the quality improvements, compared
with the preceding year. The HSMR of the trust fell from
89.6 in 2006-7 to 71.1 in 2007-8 to become the lowest
among acute trusts in England. 255 fewer deaths occurred
in the trust (174 of these in the targeted diagnoses) in
2007-8 for the HSMR diagnoses than if the 2006-7 HSMR
had been applicable. From 2006-7 to 2007-8 there was a
5.7% increase in admissions, 7.9% increase in expected
deaths, and 14.5% decrease in actual deaths.
Lessons learnt Implementing care bundles can lead to
reductions in death rates in the clinical diagnostic areas
targeted and in the overall hospital mortality rate.
About 7% of hospital admissions are associated with
adverse events, of which about 8% result in death, and
about half of the adverse events are avoidable.1 2 The hos-
pital standardised mortality ratio (HSMR), a comparative
measure of a hospital’s overall mortality, focuses on a group
“the authors’ main outcome
metric is a comparison
between death rates in
2006-7 and 2007-8, based
on hospital episode statistics
(HeS). However, 2008-9
HeS data have now been
available for a few months,
and the trust should have
access to even more recent
data. the key question is:
have these reductions been
asks Robert J Shaw, economic
adviser, in a rapid response
BMJ | 17 april 2010 | VoluMe 340
About 1200 care bundle sheets were used, 1000 at North-
wick Park Hospital and 200 at the other two hospital sites
in the trust.
The 95% confidence intervals were calculated for the
56 standardised mortality ratios (SMRs) that constitute the
HSMR and for the targeted and non-targeted diagnostic
groups for 2006-7 and 2007-8. The SMR for the targeted
diagnostic groups and the HSMR showed a significant
reduction, but the SMR of the non-targeted group was not
significantly reduced (fig 1).
Figure 2 compares the trust’s HSMRs from 1996-7 to
2008-9 with HSMRs for England. A funnel plot of HSMRs
of all acute hospital trusts in England in 2007-8, shows that
the trust’s HSMR reduced from 89.6 in 2006-7 to 71.1 in
2007-8, the lowest in England (see bmj.com).
We calculated the number of deaths that would have
occurred in 2007-8 if the relevant 2006-7 mortality ratio
had applied, and compared this with observed deaths in
2007-8. There were 83 fewer deaths in the non-targeted
diagnoses and 174 for the targeted diagnoses (255 for the
In 2007-8 the crude death rate for the non-targeted diag-
noses dropped to 2.7% from 3.4% in 2006-7, to 5.7% from
6.9% for the targeted diagnoses, and to 3.7% from 4.6%
for all diagnoses.
Figure 3 shows the change from April 2006 to March
2008 of the HSMR cusum statistic (log of the odds ratio)
with time. The cusum charts for the individual targeted
diagnoses show that the charts crossed the 99% alert level
for seven of the 13 targeted diagnoses, and for the HSMR
indicating a halving of the risk of death compared with the
national value (see bmj.com).
HSMR was significantly reduced at Northwick Park
H ospital, the hospital with the highest usage of care bun-
dles, but not at the other two hospitals (see bmj.com).
This paper reports the results of implementing eight care
bundles (guidelines for effective and safe patient care) in
the North West London Hospitals NHS Trust during 2007 to
2008, targeted on reducing mortality in several diagnostic
areas with high numbers of deaths. For the 13 Clinical Clas-
sification System diagnoses that most closely covered the
The quality improvement project started on 1 April
2007. The quantitative measure used for evaluation was
the adjusted mortality for each of the 13 targeted clini-
cal diagnostic areas, as well as the change in the trust’s
overall HSMR. Adjusted mortality was determined from
monthly mortality analyses of routinely recorded hospital
episode statistics.12-15 These covered all admissions to the
Cumulative sum (cusum) charts were used to track the
changes of mortality for each diagnosis. The probability
of death is calculated for each patient admitted using
national death rates. A function (log odds ratio) of the
weighted difference between the actual deaths and the
expected deaths was plotted cumulatively.16 17 Once the
chart reaches a preset level an alert is registered, indicat-
ing double, or half, the odds of death compared with the
national death rate.
Box 1 | Care bundles used to reduce in-hospital mortality
Central venous catheter/line asepsis
Diarrhoea and vomiting
Ventilator acquired pneumonia
Meticillin resistant Staphylococcus aureus infections
Surgical site infections
Chronic obstructive pulmonary disease
Box 2 | Targeted diagnoses from Clinical Classification
Peritonitis and intestinal abscess
Senility and organic mental disorders
Pleurisy pneumothorax pulmonary collapse
Aspiration pneumonitis food/vomitus
Skin and subcutaneous tissue infections
Urinary tract infections
Acute cerebrovascular disease
Other gastrointestinal disorders
Septicaemia (except in labour)
Chronic obstructive pulmonary disease and bronchiectasis
Congestive heart failure non-hypertensive
Fig 1 | Hospital standardised mortality ratios (HSMRs) 2006-7
and 2007-8, calculated with 2007-8 national baseline; bars
indicate 95% confidence intervals
Fig 2 | Hospital standardised mortality ratios (HSMRs) for
North West London Hospitals NHS Trust and England, using
2007-8 reference baseline (England=100); bars indicate 95%
2000-1 2001-22002-32003-4 2004-52005-6 2006-72007-8
BMJ | 17 april 2010 | VoluMe 340 863
eight care bundles used, and also for all 56 diagnoses used
to calculate the overall hospital standardised mortality rate,
the adjusted death rate was significantly lower in 2007-8
than in 2006-7. In the intervention period 174 fewer deaths
occurred in the targeted diagnoses, and 255 fewer deaths
in all diagnoses, than if the 2006-7 adjusted death rates
applied in 2007-8.
The trust’s HSMR fell from 89.6 in 2006-7 to 71.1 in
2007-8 to become the lowest of the English acute trusts
that year. This reduction became significant about one
month after the start of the quality improvement initiative.
HSMRs have been reducing in England since 2001-2, and
from 2004-5 to 2007-8 the reduction in our trust (45.7) was
greater than the England reduction (19.2) and proportion-
ately greater during 2007-8, when the reduction for Eng-
land was 6.2 and for our trust was 18.7.
Northwick Park Hospital used five sixths of the total care
bundles used in the trust. It was the only one of the three
hospitals in the trust with a significant reduction of HSMR
from 2006-7 to 2007-8.
A limitation of this type of study is the difficulty establish-
ing a causal link between introducing the care bundles and
the reduced mortality. However, the significant reduction in
mortality occurred only at the site where the care bundles
were predominantly used; it occurred in the year in which
the care bundles were introduced, starting in the month of
introduction; and it occurred for the targeted diagnoses and
not for the not-targeted diagnoses.
There could have been a Hawthorne effect related to the
participants in the project knowing that they were being
monitored.18 There could also have been a contamination
effect because the clinicians would have treated patients
with both targeted and non-targeted diagnoses, but this
would most likely have reduced the difference between the
Two earlier UK studies using HSMRs have reported simi-
lar mortality reductions to ours.19 20 In the United States
the “100,000 Lives” campaign recruited more than 3000
hospitals to a mortality reduction project that made some
use of care bundles and HSMRs.21
The methods described in this study could be generally
applicable. Monthly analyses of adjusted death rates are
routinely used by about 67% of acute hospitals in England
and make monitoring changes in mortality relatively simple.
These methods could be used to monitor whether mortal-
ity reduction continues over time and whether other care
bundles are effective.
We thank the many excellent clinicians at North West london Hospitals NHS
Trust for their collaboration. Derek Bell was external adviser in the early stages
of developing the acute assessment unit and supported the care bundle
concept and Theresa Murphy was the project leader. Dr Foster intelligence
provided access to adjusted death rates data and the institute for Healthcare
improvement gave advice on the use of care bundles. Frank Davidoff, paul
Batalden, paul aylin, alex Bottle, Gareth parry, Joanne Zaborowski, and
Steve Middleton read and commented on the paper. We found the SQuire
guidelines (www.squire-statement.org) particularly helpful.
Contributors: see bmj.com.
Funding: No separate funding.
Competing interests: ER, GS, CH, and RT work at the North West London
Hospitals NHS Trust. BJ is Director of the Imperial College Dr Foster unit,
advises Dr Foster Intelligence, and is part time senior fellow at the Institute for
provenance and peer review: Not commissioned; externally peer reviewed.
Vincent C. Understanding and responding to adverse events. 1
Vincent C. Incident reporting and patient safety. 2
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North West London Hospitals NHS Trust. Healthcare Commission, 2005.
BBC News. Drug trial victims given £10,000. 27 April 2006. 5
Institute for Healthcare Improvement. Raising the bar with bundles: 6
treating patients with an all-or-nothing standard. April 2006.
National Institute for Health and Clinical Excellence. www.nice.org.uk 7
Department of Health. National Institute for Health and Clinical 8
Excellence (NICE) clinical guidelines: 14th wave. April 2007.
Agency for Healthcare Research and Quality. Clinical practice 9
guidelines archive. www.ahrq.gov/clinic/cpgarchv.htm
Centers for Disease Control and Prevention. Guidelines by topic. http://10
Elixhauser A, Andrews RM, Fox S. Clinical classifications for health 11
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1984-1995. Stationery Office, 2001. www.bristol-inquiry.org.uk.
(Chapter 27: Care of an Appropriate Standard, Paragraph 51.)
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performance using risk-adjusted cumulative sum charts. Biostatistics
Breslow NE, Day NE. Statistical methods in cancer research, volume 17
ii: the design and analysis of cohort studies. International Agency for
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Mayo E. The human problems of an industrial civilization. Macmillan, 18
Jarman B, Bottle A, Aylin P, Browne M. Monitoring changes in hospital 19
standardised mortality ratios. BMJ 2005;330:329.
Wright J, Dugdale B, Hammond I, Jarman B, Neary M, Newton D, et al. 20
Learning from death: a hospital mortality reduction programme. J R Soc
McCannon CJ, Schall MW, Calkins DR, Nazem AG. Saving 100 000 lives 21
in US hospitals. BMJ 2006;332:1328-30.
accepted: 8 February 2010
N Engl J
Fig 3 | In-hospital mortality for the 56 diagnoses leading to
80% all deaths. Rising line indicates reducing mortality; X
shows the 99% alert level has been reached, indicating a
halving of the risk of death. Figures in parentheses show the
number of patients involved at each time for calculations
starting on 1 April 2006
Date of discharge (number of patients)
Cusum statistic - positive
Apr 06 (34)
Jun 06 (5557)
Sep 06 (10 980)
Nov 06 (16 158)
Feb 07 (21 842)
May 07 (27 448)
Jul 07 (33 233)
Oct 07 (38 890)
Jan 08 (44 794)
Mar 08 (50 707)
BMJ | 17 april 2010 | VoluMe 340
sense was reduced to the costal margins, proprioception
to the ankle, and pinprick to mid-foot level.
Magnetic resonance imaging showed T2 signal abnor-
mality in the posterior cervical cord at C2-4 (figure).
Electrophysiology found lower limb motor abnormalities
consistent with a motor neuronopathy, but sensory nerve
action potentials were normal. Central motor conduction to
the limbs (a method for examining the central motor path-
ways, in which the difference between the latency of motor
evoked potentials and peripheral conduction time is deter-
mined) indicated corticospinal disease. There was evidence
of normochomic normocytic anaemia, thrombocytosis, and
relative lymphopenia. Serum copper and caeruloplasmin
were both low (table). He was treated with intravenous cop-
per acetate solution equivalent to 2 mg a day for 10 days,
followed by oral copper acetate 8 mg a day, reduced to a
maintenance dose of 2 mg, which he continues to take. One
year later he had regained his normal weight, he walked
without an aid, and performance on the Romberg test was
improved. His pain and other neurological signs did not
improve, but the abnormalities in his full blood count and
biochemical profile resolved fully (table).
A 37 year old man presented in 1999, at another hospital,
with poor balance in the dark and tingling and burning in
his toes. Over the following year, his sensory symptoms
ascended to his chest, hands, and forearms. Examination
showed a positive Romberg’s sign. Visual acuity was reduced
to 6/12 (right) and 6/18 (left) after pinhole correction, but
otherwise cranial nerve examination, including fundoscopy,
was normal. He had full power and flexor plantar reflexes.
Light touch and pinprick sensation were impaired in his legs,
distally in his arms, and in a shield-like distribution over his
chest. Vibration sense was absent up to the jaw. Joint posi-
tion sense was impaired in the toes and fingers.
Investigations at first presentation identified anaemia,
with vitamin B-12 and folate deficiency, but when these
were corrected by his general practitioner he continued to
deteriorate. He was referred to our unit for a second opinion
in 2002. On close questioning we discovered that for sev-
eral years he had consumed more than four litres of a cola
drink per day. He had lost his teeth, and his dentures were
anchored with dental cement (Super Poligrip Ultra Fresh
denture adhesive cream, GlaxoSmithKline), which he used
in large amounts (a 68 g tube every three days). By this time
he had developed mild weakness of ankle dorsiflexion, and
the abnormality of light touch and pinprick sensation had
progressed to C2 level, sparing his face and a narrow strip
over the middle of his back. Investigations found microcytic
anaemia, neutropenia, and lymphopenia. B-12 and folate
concentrations were now in the normal range. Serum cop-
per was low, with low caeruloplasmin and raised serum zinc
Copper deficiency often goes undiagnosed
Patients presenting with a neurological syndrome typical
of B-12 deficiency may actually be manifesting symptoms
of copper deficiency, as has been recognised over the past
decade.1 Most commonly, they have a progressive spinal
cord syndrome resulting in poor balance due to loss of prop-
rioception. The cases we report show that copper deficiency,
which has various causes, is more common than previously
realised and often goes undiagnosed. Increased awareness
of this condition is vital because early diagnosis and treat-
ment can prevent severe disability.
A 65 year old man presented in 2006, having fallen in
the shower on closing his eyes; he had burning and tight-
ness affecting his feet and had recently lost weight. Over
six months he became bedbound due to poor balance. He
had undergone partial gastrectomy in 1973 for a duode-
nal ulcer. Three years before the neurological symptoms
developed, he was diagnosed with asymptomatic B-12
deficiency, which was successfully treated.
Initial examination showed a positive Romberg test and
an inability to walk heel-to-toe. Cranial nerve examination
was unremarkable. Tone and power were normal, ankle
jerks were depressed, and one plantar reflex was exten-
sor. Over six months he developed spastic weakness in his
legs (hip flexion MRC grade 4), hyper-reflexia, and bilateral
extensor plantar reflexes. Sensory disturbance suggested
greater abnormality in the posterior columns; vibration
leSSon oF tHe Week
Copper deficiency as a treatable cause of poor balance
Zhaleh Khaleeli,1 Daniel G Healy,2 Anthony Briddon,3 Michael P Lunn,2 Mary M Reilly,2 John Land,3
1Department of Neurology, National
Hospital for Neurology and
Neurosurgery, London WC1N 3BG
2MRC Centre for Neuromuscular
Diseases, National Hospital for
Neurology and Neurosurgery,
Queen Square, London WC1N 3BG
3Neurometabolic Unit, National
Hospital for Neurology and
Neurosurgery, London WC1N 3BG
4Department of Clinical
Neurosciences, Barts and the
London School of Medicine and
Dentistry, London E1 2AT
Correspondence to: G Giovannoni
Cite this as: BMJ 2010;340:c508
T2 weighted MRI shows high signal in the cervical cords of
BMJ | 17 april 2010 | VoluMe 340 865
(table). Magnetic resonance imaging showed extensive T2
signal abnormality in the posterior aspect of the entire cervi-
cal cord (figure). Electrophysiology suggested a pure sensory
neuropathy or neuronopathy. Visual evoked potentials were
delayed in the left optic nerve.
He was treated with 2 mg of intravenous copper chloride
in 250 ml of normal saline on three consecutive days, and
for five days after one and four months. After the third treat-
ment his haemoglobin concentration and white cell count
became normal, and after further oral copper replacement
his copper, caeruloplasmin, and zinc concentrations were
also normal (table). His symptoms have not improved but
he is neurologically stable. Oral copper supplementation
has been stopped, and his copper and zinc concentrations
Copper is an essential component of proteins and metal-
loenzymes in the central nervous system. Copper deficient
sensory ataxia, called swayback disease, has been recog-
nised for decades in ruminant animals but only recently in
humans.2 Over the past decade a wide variety of neurologi-
cal syndromes secondary to acquired copper deficiency have
been reported.3 Malabsorption secondary to gastric surgery
is the commonest cause,4 followed by hyperzincaemia (zinc
excess causes up-regulation of the metallothionein trans-
porter, for which zinc competes with copper; copper has a
higher affinity for metallothionein, remains bound to it, and
is shed into the intestinal tract5).
In case 1, gastrectomy—which was widely performed for
peptic ulcer disease before the 1990s—is the likely cause of
hypocupraemia. Recognised complications of gastrectomy,
which may occur acutely or decades after surgery,6 include
B-12 deficiency, but hypocupraemia is rarely considered.
The mildly raised serum zinc and markedly raised urinary
zinc concentrations, in the absence of an exogenous source
of zinc, are in keeping with other studies and may be a sec-
In case 2 the high levels of zinc raised the possibility of
an external source. Our laboratory analysis of the cola drink
did not find high zinc content; the only exogenous source
of zinc identified was the dental cement, which contained
polymethylvinylethermaleic acid, a calcium-zinc salt. After
he switched to a dental adhesive with lower zinc content
(Super Poligrip Free, GlaxoSmithKline), the patients’ indi-
ces became normal even though oral copper was stopped.
Hyperzincaemia and hypocupraemia have been associated
with overuse of dental cement,7 10 and four patients report-
edly developed neurological symptoms after using dental
cement in similar quantities to case 2, which is far in excess
of the recommended daily zinc intake.11 Whether the asso-
ciation between hyperzincaemia and dental cement is wide-
spread remains difficult to prove.
We also considered whether the cola drink contributed
to the symptoms of hypocupraemia in case 2. An associa-
tion with the sugars used in soft drinks has been reported in
rats,12 but a link has not been proved in humans.13
Copper is necessary for the integrity of the red blood cell
membrane, and as a caeruloplasmin component it is vital for
oxidation and transport of ferrous iron,14 hence the hypoc-
aeruloplasminaemia and anaemia seen in our patients, and
the abnormal results of iron studies and bone marrow find-
ings in case 2. Neutropenia, and rarely pancytopenia,15 as
well as thrombocytosis,16 have also been described, although
the mechanisms remain unclear. Although both patients had
low concentrations of vitamin B-12 initially, case 1 had been
treated before the onset of neurological symptoms, and in
case 2 symptoms did not improve with treatment. B-12 defi-
ciency commonly coexists with hypocupraemia,17 and both
result in myeloneuropathy. In addition, both our patients
had similar features on magnetic resonance imaging, typical
of B-12 myelopathy.18 This underlines the importance of con-
sidering hypocupraemia in patients with symptomatic B-12
deficiency who do not improve with treatment.8 Further neu-
rological deterioration is prevented by copper replacement,
and limited improvement is seen in some cases.2 8- 10 19
Given the number of gastrectomies performed, and the
multiple potential sources of zinc ingestion, copper defi-
ciency may be underdiagnosed. Cases of copper deficiency
have been reported when zinc has been used to treat acro-
dermatitis hepatica and sickle cell anaemia, and when it
has been taken prevent common colds.7 20 21 Zinc is also
used to promote ulcer healing7 and in multivitamin prepa-
rations. Practitioners should measure serum copper levels
in all patients presenting with predominantly posterior col-
umn spinal cord dysfunction (disproportionate loss of joint
position and vibration sense). Peripheral neuropathy, leg
spasticity, altered full blood count, and a history of B-12
deficiency may also be present. Greater recognition of this
syndrome is vital to prevent irreversible disability.
Investigations before and after copper replacement
Test (normal range)
Haemoglobin (130-170 g/l)
White cell count (3-10×109/l)
Mean corpuscular volume (80-99 fl)
Platelets (150-400 ×109/l)
Vitamin B-12 (180-700 ng/l)
Red cell folate (150-650 µg/l)
Serum iron (9-30 µmol/l)
Total iron binding capacity (45-70 µmol/l)
Iron binding sat (20-50%)
Ferritin (µ22-275 g/l)
Serum copper (11-21 µmol/l)
24 hr urinary copper (0.2-1.0 mmol/l/24h)
Serum zinc (11-18 µmol/l)
Caeruloplasmin (1.1-2.7 µmol/l)
In both patients, these test results were normal or negative: electrolytes and plasma glucose; liver function
tests, albumin; thyroid function tests; clotting factors; plasma homocysteine, organic and amino acid profile,
other B vitamins including B-6, vitamins A, D, and E (to exclude functional B-12 and other vitamin deficiencies);
antibodies against intrinsic factor, parietal cells, reticulin, and gliadin, anti-endomysial antibodies (to exclude
coeliac disease); antiphospholipid antibodies, autoimmune screen, HTLV 1 and 2, TPHA (treponema pallidum
haemagglutination test), oligoclonal bands (to screen for other causes of myelopathy: antiphospholipid
syndrome, connective tissue diseases, tropical spastic paraparesis, syphilis, and demyelinating diseases).
In case 1, bone marrow examination was normal; in case 2 it was normocellular with erythroid predominance,
supporting a peripheral cause for neutropenia. Iron stores were reduced, and there was evidence of cytoplasmic
In case 2 a penicillamine challenge excluded Wilson’s disease (which can paradoxically reduce serum copper).
A small bowel biopsy (to screen for malabsorption) was normal. Genetic testing for acaeruloplaminaemia, a rare
cause of low caeruloplasmin, was negative.
— = test not carried out.
*At least six months after start of oral maintenance regimen.
Case 1 Case 2
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complications of gastric bypass surgery for morbid obesity. Neurology
Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, 7
Levinson BS et al. Zinc-induced copper deficiency: a report of three
cases initially recognized on bone marrow examination. Am J Clin
Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy 8
produces a clinical picture like subacute combined degeneration.
Prodan CI, Holland NR, Wisdom PJ, Burstein SA, Bottomley SS. CNS 9
demyelination associated with copper deficiency and hyperzincemia.
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Myelo-optico-neuropathy in copper deficiency occurring after partial
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occult zinc ingestion tip the balance? J Neurol 2007;254:1012-7.
endgames picture quiz: More than skin deep?
We mistakenly published the name of only the first
author (Mark J Austin) of the three authors of this article
(BMJ 2010;340:c932, print publication 6 March,
p 541). The second and third authors are Shaheed Islam,
foundation year 1 doctor, and Paul Kitchen, consultant,
both from the department of gastroenterology, Medway
Maritime Hospital, Gillingham.
Management of obesity: summary of SiGn guideline
Owing to a processing error, this Practice article by
Jennifer Logue and colleagues (BMJ 2010;340:c154,
print publication 27 Feb, pp 474-7) was not updated
to take account of the withdrawal in Europe in
January 2010 of sibutramine, formerly a drug used
to treat obesity. In two places, therefore, the article
should say: “Consider orlistat” [not “Consider orlistat
or sibutramine”]. Orlistat is now the only drug
recommended in the treatment of obesity.
complications: tracking down the data on oseltamivir
In this Features article by Deborah Cohen (BMJ
2009;339:b5387, print publication 12 Dec, pp 1342-7)
we missed out the “h” in Hanna Rhind’s surname
Preventing alcohol related harm to health
In the second paragraph of this editorial by Trish Groves
(BMJ 2010;340:c372, print publication 23 Jan, pp 161-2)
we mistakenly referred to Miller as being the author of a
linked article in the same issue that was in fact written
by Claire Harkins (BMJ 2010;340:b5659, p 187).
news: in brief
An item titled “Mefloquine may contribute to mental
health problems in troops” in the “In brief” column
of the news section (BMJ 2010;340:c162, print
publication 16 Jan, p 122) did not correctly summarise
the results of a research report that we were reporting
The item said that “One in seven (14%) US military
personnel deployed to Afghanistan in 2007 who were
given mefloquine had known contraindications to it,”
whereas we should have said: “One in 29 (3.4%) US
military personnel deployed to Afghanistan in 2007
who were given mefloquine had known (documented)
contraindications to it.” However, among those with
known contraindications, mefloquine was indeed
inappropriately prescribed to 1 in 7.
Home based versus centre based cardiac rehabilitation:
cochrane systematic review and meta-analysis
The authors of this paper, Hasnain M Dalal and
colleagues, have alerted us to errors in the figure (BMJ
2010;340:b5631, print publication 30 Jan, p 249). The
column headings in the forest plot and the labelling
under the forest plot (Centre based and Home based)
should be reversed. This does not affect the conclusions
of the paper.
research online box
The first item in this information box (BMJ 2010;340,
print publication 6 Feb, p 299) refers to venlafaxine
as a “selective serotonin receptor inhibitor.” A reader
has reminded us there is no such thing, that there are
selective serotonin reuptake inhibitors but venlafaxine
isn’t one of them. Venlafaxine is a serotonin and
noradrenaline reuptake inhibitor.
if only WHi was done well
In this letter by John C Stevenson and colleagues
about the women’s health initiative (WHI) trial (BMJ
2010;340:c591, print publication 20 Feb, p 382),
the difference in ovarian cancer incidence between
hormone replacement therapy and placebo was, as we
said, non-significant, but we then wrongly added a
P value of 0.02 during editing.
Corrections and clarifications
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