Critically analyse the manuscript, ‘External validation of clinical decision rules for children with wrist trauma’. Identify the strengths and gaps in the clinical decision rule used by Mulders et al.

Question 1
(20 marks) Consider this case study:

A 55-year-old male presents to the ED complaining of chest pain for the past two days. His pain is substernal and non-radiating. The patient’s description was tightness but not related to exertion. The male patient has no associated shortness of breath, nausea or diaphoresis, no cough or fever and the patient has never had this pain before. However, the patient does have a history of hypertension. Does this patient require additional cardiac care in the ED or should he be admitted to hospital for further follow-up or can the patient be safely discharged for outpatient follow-up?

Decision Making in Health may be overcome by using the PROACTIVE (problem-reframe-objectives-alternatives-consequences and chances- trade-offs-integrate-value-explore-evaluate) approach. This comprehensive approach to clinical decision-making considers all advantages and disadvantages prior to taking action. Use the stepped PROACTIVE approach to help in your decision analysis to treat this patient. Make sure to clearly identify each step and provide supporting evidence (using published literature). Answers should not exceed 500 words for each part.

Step 1 PRO:

(Problem-Reframe-Objective):

Define the problem, consider all perspectives (i.e., the patient, the clinician, and the healthcare service), and focus on the objective (what is the medical effectiveness, diagnostic uncertainty etc). (5 marks)

Step 2 ACT:

(Alternatives-Consequences-Trade-offs): Use the literature to provide you with some evidence about the potential interventions. Consider the information from the literature to create a hypothetical decision tree, balance sheet or Markov cohort model. Include possible outcomes and potential probabilities. Provide references for your decisions. (9 marks)
Step 3 IVE:

(Integrate-Value-Explore-Evaluate): Using the decision tree, balance sheet or Markov cohort model from part (ii) above, determine the desirable and undesirable outcomes. Discuss the clinical decision that leads you to the most appropriate outcome. Justify your answer. (6 marks)
Question 2

Question 2 Part (A) (6 marks) In this two-part question, you are required to produce decision making models based on recurring events using Cohort simulation and Markov modelling.

Cohort simulation:

In 1981, the first case of human immunodeficiency virus (HIV), which is the etiological agent for acquired immunodeficiency syndrome (AIDS), was diagnosed in the USA and has since been defined as a sexually-transmitted disease throughout the world. Consider a cohort of 20,000 patients who have contracted the disease. Patients may be classified as being in one of three possible states: well, active disease, deceased. The transition probabilities for each cycle imply that there is a 0.65 chance a patient’s disease will be under control with the treatment, a 0.25 chance that the disease will be active but the patient will be unwell and a 0.1 chance that the patient will die.

Provide a graphical display of the transitions through three cycles (2 marks)
Provide a Markov trace of the first ten cycles or until all patients have died. (2 marks)
If we are to terminate the simulation when the fraction of the cohort remaining alive and well falls below the 5% threshold, at what cycle of the simulation would this occur and how many patients in this hypothetical cohort would still be well? (2 marks)

Question 2 – Part (B) (10 Marks) Markov model:

Human Papilloma Virus:
According to the Health Canada Web site (www.hc-sc.gc.ca), “HPV is likely one of the most common sexually transmitted infections (STIs) in Canada”. Several types of HPV are known to circulate in the population. Some types lead to genital warts, while others lead to cancers. The virus is often asymptomatic and can switch between active and inactive states.

Screening programmes have been established to detect and treat early instances of infection-related diseases.

Develop the model (hypothetical) for HPV transmission. Your health states are: cervical screening (healthy), HPV exposure (potentially infected), diagnosis of STIs (genital warts), diagnosis of cancer (cervical etc), and early treatment.

Assume that from the healthy state, women being screened have a 35% chance of a positive HPV test, all other women stay in a healthy state. For those with HPV exposure there is a 31% chance that they are deemed well, 5% chance that the women stay in the HPV exposed state for retest, 14% chance of cervical cancer, 13% chance of genital warts and 37% chance of receiving early treatment.

Women that have a diagnosis of cervical cancer have an 80% chance of receiving early treatment while the remainder stay in the same state. Women that have a diagnosis of genital warts have a 62% chance of receiving early treatment, 2% chance of staying in the same state or are deemed well and healthy otherwise.

Women that receive early treatment have a 2% chance of staying in the same state, failure of early treatment returns 30% to cervical cancer and 5% to genital warts with others deemed well and healthy otherwise.

Provide a transition matrix to show the model’s probabilities. (2 marks)
Graphically show all the transition probabilities for the HPV pathways, modelled as a Markov chain. (3 marks)

Consider the long-term predictions of women’s behaviour over time among 20,000 young women who are healthy and regularly have cervical screening. What is the likelihood of having a positive HPV test, followed by a diagnosis of genital warts, given early treatment then returning to a healthy state? (2 marks)

Of the women that contract genital warts, what is the likelihood they will develop cervical cancer? Provide the probability and the number of women. (2 marks)

If this were a real-world model, which important health state has been overlooked? (1 mark)

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Question 3

(14 marks) Critically analyse the manuscript, ‘External validation of clinical decision rules for children with wrist trauma’. Identify the strengths and gaps in the clinical decision rule used by Mulders et al. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391386/)
Answers in any part should not exceed 500 words.

Identify and define the problem. (2 marks)

Have the authors provided a thorough examination of the literature? Discuss the method and terms used (3 marks)

Examine the three previous studies the authors have evaluated (Pershad, Webster and Rivara). Were these studies appropriate for comparison and to validate the clinical decision rule? (5 marks)

The authors compare their results with the Amsterdam Paediatric Wrist rules study. Discuss. (2 marks)
Suggest anything that could have been done better. (2 marks)

Suggested extra reading material:

Question 3 Suggested reading: ‘A clinical decision rule for the use of plain radiography in children after acute wrist injury: development and external validation of the Amsterdam Pediatric Wrist Rules’ by Slaar ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706582/ )

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