Den gode artikel

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Den gode artikel

• Christian Torp-Pedersen

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Først ansøgning om penge NIH

• Regn med at 2 bedømmere har læst ansøgningen
• Regn med at resten af udvalget læser på dit 1
  page summary samtidigt med at de hører en
  mundtlig gennemgang af en bedømmer

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(No Transcript)
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Et godt abstract

• En, højst to sætninger som forklarer hvorfor
  dette er ekstremt vigtigt
• Et kort metodeafsnit, det bliver næppe læst
• Et svulstigt resultatafsnit et abstract skal
  bestå af MANGE resultater
• En direkte konklusion på baggrund af de
  resultater som er nævnt i abstract uden for meget
  implikation

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Abstract a.m. John Camm

• A title with at least one buzz word
• A strong first sentence
• A strong conclusion
• All that rest in the middle just becomes a blurr

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Danish Investigations of Arrhythmia and Mortality
ON Dofetilide
DIAMOND
8
Overall Survival - Intention to Treat
1.0
Dofetilide - 311 deaths
0.8
Dofetilide (n762)
Placebo (n756)
0.6
Placebo - 317 deaths
Survival
0.4
0.2
Overall RR 0.95, 95 CI 0.811.11
P0.56
0.0
0
12
24
36
Months
9
Secondary Endpoints
Arrhythmia requiring treatment withdrawal
Cardiac deaths resus. C.A.
Recurrent MI
1.0
0.8
0.6
0.4
0.2
P0.79
P0.78
P0.90
0.0
0
0
1
2
3
1
2
3
1
2
0
3
Event Free Probability
Years
Years
Years
Events in patients with AF
Cardiac death
1.0
0.8
Dofetilide (n762)
Placebo (n756)
0.6
0.4
0.2
P0.89
P0.71
0.0
0
0
1
2
3
1
2
3
Years
Years
10
Ventricular Arrhythmia (Total)
Dofetilide n762
Placebo n756
12 (57)
14 (311)
VF
RCA
19
4
4 days
19
12
gt4 days
38
16
TOTAL
4
0
Death
4 days
317
307
gt4 days
311
317
TOTAL
Number with resuscitated cardiac arrest-death in
parenthesis
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Effect of Dofetilide on Atrial Fibrillation
No of patients enrolled in NSRwho developed AF
No of patients enrolled in AFwho converted to NSR
50
100
84
40
n1125 Plt0.001
35
75
n393 Plt0.001
30
50
20
28
11
25
10
0
0
Placebo
Dofetilide
Placebo
Dofetilide
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God dansk indledningt

• Cardiac arrhythmias are common in patients with
  congestive heart failure (CHF), contributing to
  both mortality and morbidity. The possibility of
  reducing morbidity has so far been overshadowed
  by severe safety concerns with antiarrhythmic
  drugs. Some class I drugs1 and the class III drug
  d-sotalol2 increase mortality in patients with
  myocardial infarction. Amiodarone appeared to
  prolong life in one CHF study,3 but this finding
  was not confirmed in Survival Trial of
  Antiarrhythmic Therapy in Congestive Heart
  Failure study,4 which showed no effect on
  mortality. A neutral outcome was also found in
  two other studies including some CHF patients.5,6
  Amiodarone is frequently used to treat
  arrhythmias in patients with CHF, but the
  considerable long term side effects limit its
  use. Digoxin has demonstrated safety in CHF in
  the Digitalis Investigation Group trial7 and is
  commonly used for rate control in atrial
  fibrillation associated with CHF.
• Dofetilide is a selective inhibitor of the rapid
  component of the delayed rectifier, outward
  potassium current (IKr), which prolongs the
  action potential duration and the effective
  refractory period in a concentration dependent
  manner. Clinical studies have demonstrated that
  the drug is effective in treating atrial
  fibrillation and flutter.8,9 As with other class
  III anti-arrhythmic drugs, dofetilide can cause
  proarrhythmia but the incidence is yet to be
  defined.
• The Danish Investigations of Arrhythmia and
  Mortality ON Dofetilide (DIAMOND) studies are two
  distinct studies investigating whether a
  reduction in mortality and morbidity can be
  achieved by long term dofetilide treatment in
  patients with left ventricular systolic
  dysfunction and either CHF or a recent myocardial
  infarction. This publication describes the
  results of the congestive heart failure study
  (DIAMOND-CHF)

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Prøver igen

• Prevention of ventricular and supraventricular
  arrhythmias in patients with congestive heart
  failure is an important goal with the object of
  reducing mortality and morbidity. A series of
  antiarrhythmic drugs have been tested in clinical
  trials without success. Thus, several class 1
  drugs and the class III drug d-sotalol have been
  demonstrated to be associated with increased
  mortality compared to placebo. Amiodarone has in
  a single survival study been demonstrated to
  reduce mortality, but this observation has not
  been confirmed in a series of other studies.
  Amiodarone is associated with frequent side
  effects that may be serious, and which has
  prevented the possibility of using this drug on a
  wide scale for non- lifethreatening conditions.
  The Danish studies of arrhythmia and mortality on
  dofetilide were designed to study the possibility
  of reducing mortality and morbidity in patients
  with congestive heart failure using the novel
  class III antiarrhythmic drug dofetilide. This is
  a selective inhibitor of the rapid component of
  the delayed rectifier, outward potassium current
  (IKr), which prolongs the effective refractory
  period. There is no effect on ATP dependent
  potassium channels. Clinical studies have
  demonstrated that the drug is particularly
  effective in treating patients with atrial
  arrhythmias. The target population in the Diamond
  CHF study was high risk patients with congestive
  heart failure. To ensure that the population
  would be as representative as possible of these
  patients as seen in clinical practice screening
  of consecutive patients admitted to hospital was
  specifically required. The primary endpoint was
  all cause mortality and the possibility of
  reducing morbidity was studied by having
  hospitalisation for worsening of heart failure as
  one secondary endpoint.

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Final

• Congestive heart failure is a serious disease
  that may be exacerbated by many factors unrelated
  to ventricular dysfunction. One factor that is
  important in determining the symptoms and
  clinical course of patients with severe
  congestive heart failure is the maintenance of
  normal sinus rhythm. Unfortunately, atrial
  fibrillation (AF) is common in patients with
  heart failure and can impair exercise tolerance
  and exacerbate symptoms by causing loss of atrial
  contraction, leading to hemodynamic and
  thromboembolic consequences, or by increasing the
  rapidity of the ventricular response leading to
  tachycardia and a shortened diastolic filling
  period.14 Although digitalis can attenuate the
  ventricular response at rest, it fails to do so
  during exercise and thus does not eliminate the
  effect of AF on exercise tolerance.5 In
  addition, previous studies have shown that AF
  increases the risk of cardiovascular morbidity in
  patients with heart failure.6 Hence, prevention
  of AF or conversion of AF are worthwhile goals in
  patients with congestive heart failure.
• Currently available drug therapy to prevent or
  convert AF can have adverse effects that are
  possibly detrimental in patients with heart
  failure, including an increase in mortality.7
  Heart failure patients receiving class I drugs
  for AF in the SPAF trial had a 3-fold increase in
  mortality and arrhythmic deaths.7 Quinidine
  therapy has also been associated with a 3-fold
  increase in mortality.8 The only exception has
  been the class III drug, amiodarone, which has
  been associated with favorable effects in heart
  failure.9,10 However, this drug is frequently
  associated with serious cardiac and noncardiac
  side effects.11
• Dofetilide is a novel class III antiarrhythmic
  drug that selectively inhibits the rapid
  component of the delayed rectifier potassium
  current (IKr) and prolongs the effective
  refractory period.1214 As a pure class III
  agent, it has no negative inotropic effects, even
  in patients with a markedly reduced left
  ventricular ejection fraction.15 In addition,
  dofetilide has no effect on cardiac conduction or
  sinus node function in patients with pre-existing
  cardiac disease.15,16 Dofetilide has been shown
  to convert AF to sinus rhythm and is effective
  for maintaining sinus rhythm in 70 of patients
  for at least six months.17,18
• The DIAMOND-CHF (Danish Investigations of
  Arrhythmia and Mortality on Dofetilide) study was
  designed to evaluate whether dofetilide affects
  survival or morbidity in patients with reduced
  left ventricular (LV) function and congestive
  heart failure.

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Hvem er publikum?
16
Hvem er publikum?

• En editor
• To referees

17
Hvem er publikum?

• En editor
• To referees
• Editor ved intet
• Referees ved meget lidt

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Introduktion

• Et formål At forklare hvorfor en travl editor
  skal læse videre
• Fortæl hvorfor dit arbejde er nødvendigt

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Praktisk introduktion

• En indledning som forklarer at dette er EKSTEMT
  vigtigt
• Der er en afgrundsdyb mangel på vigtig viden om
  dette emne!
• Derfor gjorde jeg/vi ..

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Methods

• Kan som ofte hackes fra andre artikler
• Husk at skrive ALLE sætninger om
• Et kedeligt afsnit som altid kan forkortes
• Statistik skriv HVILKE metoder der anvendes, og
  ikke om HVORDAN de anvendes

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Results

• Præsentere populationen
• Undgå at gentage oplysninger
• Logisk opdeling helst med små overskrifter
• Kom kritik i forkøbet medAnalyses of
  sensitivityOther analyses
• Det centrale budskab skal være grafisk hvis det
  overhovedet kan lade sig gøre

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Resultater

• Billeder er bedre end ord

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Pfeffer 1992 - SAVE
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Variables Homozygocity for both GG and CC variants (n73) Other combinations of sequence variants (n1249) Homozygocity for both AA and TT variants (n88)
Office systolic BP, mm Hg 128.7 (124.9-132.4) 129.3 (128.3-130.2) 132.5 (129.1-135.9)
Office diastolic BP, mm Hg 81.2 (78.9-83.5) 81.5 (80.9-82.0) 84.1 (82.0-86.2)
Office heart rate, beats/min 66.1 (63.9-68.4) 65.1 (64.5-65.7) 67.4 (65.4-69.5)
Mean 24-hr systolic BP, mm Hg 123.1 (120.2-125.9) 125.4 (124.7-126.1) 129.1 (126.5-131.6)
Mean 24-hr diastolic BP, mm Hg 72.2 (70.3-74.1) 73.3 (72.8-73.8) 76.0 (74.3-77.7)
Mean 24-hr heart rate, beats/min 69.1 (67.1-71.1) 70.6 (70.1-71.1) 72.3 (70.5-74.2)
Mean daytime systolic BP, mm Hg 129.0 (126.1-131.9) 130.9 (130.2-131.6) 134.9 (132.2-137.5)
Mean daytime diastolic BP, mm Hg 76.5 (74.5-78.5) 77.2 (76.7-77.7) 80.3 (78.4-82.1)
Mean daytime heart rate, beats/min 72.8 (70.7-74.9) 73.6 (73.1-74.1) 75.7 (73.8-77.6)
Mean nighttime systolic BP, mm Hg 108.4 (105.3-111.6) 112.3 (111.5-113.1) 114.9 (112.1-117.7)
Mean nighttime diastolic BP, mm Hg 61.6 (59.6-63.6) 63.7 (63.2-64.2) 65.5 (63.7-67.3)
Mean nighttime heart rate, beats/min 60.4 (58.2-62.5) 63.5 (62.9-64.0) 64.9 (62.9-66.9)
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R
Sigmaplot
Anderson, C - upubliceret
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Vær loyal overfor protokollen Men ikke med
teksten
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Packer - 1996
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Discussion

• Statement of principal findings
• Relation til andre studier Husk ikke blot at
  skrive at andre fundet hist og pist, men fremhæv
  svaghederne og dermed indirekte egen styrke
• Metodeforhold
• Styrker og Svagheder
• Implikation
• Konklusion

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Statement of principal findings

• This is the first study to demonstrate.Ikke
  alle tidsskrifter ønsker priority claims
• The principal finding of this study

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Relation til andre studier

• Undgå generelle sætningerSimilar findings have
  also been found by
• Skriv hellere A small study by . Using a
  different technique .An older study .

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Metodeforhold

• Beskrive at ens metoder er optimale
• Undgå at skuffe læseren skriv eventuelle
  svagheder førstWhile the epidemiological
  approach has limitations, this study .

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Implication

• Ekstremt vigtigt et studie SKAL have
  konsekvenser.
• Konsekvensen kan være klinisk, metodemæssigt,
  fremtidig forskning..

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Man arbejder med hver sætning!

• These results demonstrate that the risk of cancer
  for all insulins was neutral after 1 year, but
  the confidence intervals remains high for humans
  insulins because of power.
• The power to examine human insulins was low, but
  for all other insulins the risk of cancer was
  neutral after 1 year.

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Konklusion

• Principal finding i ny indpakning

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Svarbreve til tidsskrifter

• Editor er doven
• Risikoen for at det går tilbage til reviewer er
  stor
• Reviewere har stadigt travlt

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Sørg for at de kun skal læse ET dokument EN gang

• Start med et svulstigt takkebrev
• Første kommentar af første reviewer
• Egne kommentarer til dette
• Manuskript tidligere version
• Manuskript nuværende version
• Afsnit skal være så tydelig markeret at det er
  helt intuitivt hvad der er reviewer kommentarer,
  hvad der er svar o.s.v.

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Svar!!

• Henvis gerne tilbage aldrig frem
• Lav aldrig gentagelser
• Lav gerne ligegyldige rettelser Nevertheless,
  in order to clarify this further ......
• Vær trods alt dette HELT klar i mælet når en
  kommentar tilbagevises dette skal kun være i
  yderste nød!

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• The editor
•  
• We wish to thank HEART for giving us a
  comprehensive review and for giving us the
  opportunity to have a revised manuscript
  evaluated. Below we have replied to each of the
  comments given by the referees. A principal issue
  is whether a clinical diagnosis of diabetes can
  be accepted. Ideally diabetes should be defined
  by international criteria, but this is rarely
  available in studies of clinical epidemiology.
  The majority of the literature on clinical
  epidemiology of diabetes in patients with heart
  failure and patients with ischemic heart disease
  relies on similar definitions as those we have
  used.
•  
• We hope you will consider the revised manuscript
  suitable for publication in HEART.
•  
• In the following reviewer comments are indicated
  in italic and our reply in bold text. Changes to
  the manuscript are shown in normal text.

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Sød mand!

• -- The definition of new onset diabetes is also
  confusing. The authors should
• try to indicate how many patients fulfilled the
  standard definition of diabetes
• through the study. The results refer to 2
  different types of new onset diabetes.
• This is also confusing
•  
• Our reply We acknowledge that our definition of
  new onset diabetes may be difficult to read and
  we have prepared a new section. There are NOT 2
  types of new onset diabetes in this manuscript
  but the predefined endpoint of diabetes related
  adverse event and new onset diabetes.

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Previous

• Because the diabetes-related adverse events also
  included events (hyperglycemia, decreased glucose
  tolerance) that were not necessarily diabetes, we
  subsequently defined a new endpoint
  retrospectively, new onset diabetes. This
  endpoint included all patients who either had
  either an adverse event coded as diabetes
  mellitus or diabetic coma, or who had started
  chronic medical therapy with insulin or oral
  antidiabetic medication or who had at least 2
  random blood glucose readings above 11.2 mmol/L
  (random glucose was measured 4 times during the
  first year and thereafter once a year). In
  patients in whom only a single high random
  glucose measurement was reported, we queried the
  investigator whether the patient had diabetes. If
  confirmed, the presence of an endpoint was noted.
  

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Revised

• Because the diabetes-related adverse events also
  included events (hyperglycemia, decreased glucose
  tolerance) that were not necessarily diabetes, we
  subsequently defined a new endpoint
  retrospectively, new onset diabetes. This was
  considered present if
• A clinical diagnosis of diabetes was reported. If
  the investigator reported an adverse event coded
  as diabetes mellitus or diabetic coma, or if the
  patients had started chronic medical therapy with
  insulin or oral glucose lowering therapy.
• If the patient had at least 2 random blood
  glucose reading above 11.1 mmol/L. Random glucose
  was measured 4 times during the first year and
  thereafter once a year. Random glucose was
  measured by the investigator using the local
  laboratory. Blood glucose was requested, but in
  some cases plasma glucose may have been reported.
  For this reason we used the conservative estimate
  of 11.1 as the cut-off.
• If adverse event reporting was unclear/contradicto
  ry from the original case report forms (such as
  the reporting of a single high blood glucose
  reading) and additional page was sent to the
  investigators requesting to review the patient
  file and confirm the existence of diabetes, give
  the date diabetes was diagnosed and tick the
  following possibilities need for diabetic
  medication, repeated high blood glucose results,
  a positive oral glucose tolerance test, repeated
  high fasting glucose. Only when a date (at least
  month/year) and at least one of the tick boxes
  was answered as yest was the patient classified
  as diabetic.

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• Results and discussion
• - Mortality reduction was NOT significant in
  diabetic patients. The reading of
• the abstract, and discussion suggests otherwise.
  This should be corrected
•  
• Our reply The last sentence in the result
  section of the abstract reads Both diabetics
  and non-diabetics at baseline had a similar
  reduction in mortality with carvedilol compared
  to metoprolol (RR 0.85 CI 0.69-1.06 and RR 0.82
  CI, 0.71-0.94, respectively). We clearly show
  that the confidence limits for patients with
  diabetes cross the line of unity. We consider the
  statement that mortality reduction was similar
  appropriate because there was no interaction. In
  response to this comment and in response to
  referee 2 we have changed the conclusion of the
  abstract
•  
• Old abstract conclusion
• Conclusion In patients with chronic heart
  failure, carvedilol is associated with less
  development of new onset diabetes compared to
  metoprolol. Carvedilol is superior to metoprolol
  in improving long-term outcomes in both diabetic
  and non-diabetic patients.
•  
• Revised version
• Conclusion - This study demonstrates both a high
  prevalence and incidence of diabetes in patients
  with heart failure over a course of 5 years. New
  onset diabetes was more likely to occur during
  treatment with metoprolol than during treatment
  with carvedilol.