How to write papers/manuscripts while still in fellowship

1. How to write papers/manuscripts while still in fellowship Michael Hawkes, MD, PhD

2. Objectives • To know the importance of publication during fellowship • To describe the steps of writing a scientific manuscript • To know strategies for scheduling manuscript writing during fellowship • To differentiate the role of peer reviewed publication in academic and nonacademic careers

3. Types of articles you could write: • Case report • Case series (retrospective chart review) • Case-control study (retrospective) • Prospective clinical study • RCT • Basic/translational science • Other (review articles, clinical practice guidelines, cost-effectiveness, decision analysis, etc.)

4. 1. Case Report

5. 1. Case report + - Not usually high impact Expect a long process getting it published • Relatively quick write-up (no data collection) • Fits easily into clinical workload • An interesting/unusual case, e.g., weird organism • Good practice for scientific writing

6. 2. Retrospective chart review

7. 2. Retrospective chart review + - Descriptive, no control group, retrospective data limits impact Be realistic in choice of journal (or aim high, expect rejections, and prolong time to publication) Can run into snags in analysis: e.g., missing data • Case series or case-control study • Data collection is easier than prospective studies • Faster timeline, no funding needed • Feasible in fellowship • Can pick a rare condition

8. 4. Prospective observational study

9. 4. Prospective observational study + - Takes a lot of time Not possible for any but the most common diseases in the timeframe of a fellowship Start very early Need staff and money • Higher impact • Needs attention to design, planning, sample size • Hypothesis-testing • Data collection more complete, better quality; analysis more straightforward • ? Take advantage of bio-banked samples

10. 5. RCT + - Ethics and planning will be very time-consuming $$$ Low feasibility in fellowship • High impact, if it works • Needs attention to sample size (so that a negative result is also meaningful) • Trial quality management requires a whole team • Could tag along on an existing/ongoing study (clarify authorship and “ownership” of the project)

11. 6. Basic/translational science + - Not everyone’s cup of tea Dedicated time and salary support needed Probably an add-on to a standard fellowship Opportunity cost Lots of frustrations, ideas often don’t pan out • May be intellectually rewarding • Could participate in ongoing studies • Can learn new skills, different knowledge base • Need a good supervisor

12. 7. Other • Medical education • Cost-effectiveness • Decision analysis • Review article • Clinical guideline

13. 6. Basic/translational science

14. Nitric Oxide protects blood brain barrier integrity 10.7 14.3 10.8 10.6 8.2 12.5

15. Nitric Oxide reduces parasite sequestration in the brain

16. Adjunctive iNO improves survival compared to artesunate alone

18. Angiopoietin-2 predicts mortality in severe malaria

19. Inhaled nitric oxide for severe malaria Hypothesis Supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. Children receiving adjunctive iNO will have a more rapid improvement in Ang-2. Rationale • biological plausibility, based on known actions of NO in modulating endothelial activation • pre-clinical efficacy data from animal models of experimental cerebral malaria • a human trial of the NO precursor L-arginine, which improved endothelial function in adults with severe malaria

21. Design Randomized, placebo-controlled, blinded, parallel group comparison of iNO versus room air placebo Empewo enhungi eyo musudha

22. Participants Inclusion criteria • Age 1-10 years • Positive rapid diagnostic test • Features of severe malaria: repeated seizures, prostration, impaired consciousness, respiratory distress • Willing to complete follow up schedules for the study Exclusion criteria • Baseline metHb >2% • Chronic illness: renal, cardiac, hepatic, diabetes, epilepsy, cerebral palsy, clinical AIDS. • Severe malnutrition • Severe malarial anemia without other signs of severe malaria

23. Intervention • Active treatment • iNO 80 ppm • Delivered by face mask • Up to 72 hours • Placebo • Room air as above

24. Primary Outcome: longitudinal Ang-2 Sample size: n=180 Hypothesized effect of iNO Computer Simulation : power calculation

25. Secondary Outcomes Efficacy • 48 hour and 14 day mortality • Recovery times: • time to fever resolution • time to sit unsupported • time to hospital discharge • Time to parasite clearance • Recrudescence at D14 Safety and tolerability • Methemoglobinemia Neurocognitive outcome • 6 months after discharge

33. Screening and enrolment

34. Demographic characteristics

35. Parasite density

36. Recovery times (days)

37. Mortality

38. Translational aspects • Rapid translation of findings in experimental models to a RCT in humans • Re-positioning of established pharmaceutical for a new indication: severe malaria • Ang-2 identified as a quantitative marker of disease severity • Surrogate primary endpoint • Efficient study design

39. Objectives • To know the importance of publication during fellowship

41. Objectives • To describe the steps of writing a scientific manuscript

42. Writing up (what works for me) • Start with results (figures and tables) • Fill in background and discussion • Methods: easy • Abstract last • Tell a “story” (logical flow) • Frame within the existing literature (what does the study add?) • Model after other studies

43. Objectives • To know strategies for scheduling manuscript writing during fellowship

44. Objectives • To differentiate the role of peer reviewed publication in academic and nonacademic careers

45. YOUR PICTURE HERE