public void MoveEETEfficacy(BE_State nextStateIn, BE_Cycle cycleIn)
{
status = BE_PatientStatus.Recurrence;
completedEET = true;
activeRecurrenceProbability = true;
postEETState = nextStateIn;
confirmedState = nextStateIn; // Assumption popst EET state is always confirmed.
currentState.Population--;
currentState = nextStateIn;
currentState.Population++;
needPostEETDecision = true;
if (postEETState.ID >= realPreEETState.ID) // Treatment failure. If in reality NoBarretts, it must be switched to naturel progression.
{
status = BE_PatientStatus.NaturalHistory;
activeRecurrenceProbability = false;
activeNaturalProgression = true;
}
if (postEETState.ID >= preEETState.ID) // Treatment failure is observed
{
concludedAsFailedEET = true;
}
}
public void FollowUpSurveillanceDecision(BE_Patient patientIn, BE_Cycle cycleIn)
{
if (patientIn.ConfirmedState.Type == BE_StateType.IMC || patientIn.ConfirmedState.Type == BE_StateType.SC)
{
patientIn.NextTreatment = cycleIn.ID;
}
else if (patientIn.ConfirmedState.ID > patientIn.PostEETState.ID && patientIn.CompletedMaxRFA == false && patientIn.FailedEET == false)
{
patientIn.NextTreatment = cycleIn.ID;
}
else
{
if (patientIn.PreEETState.Type == BE_StateType.NDBE || patientIn.PreEETState.Type == BE_StateType.LGD) // Assumption: If there is no adherence, the follow-up intervals continue.
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalLGD[Math.Min(patientIn.CountFollowUp, postIntervalLGD.Length - 1)];
}
else if (patientIn.PreEETState.Type == BE_StateType.HGD || patientIn.PreEETState.Type == BE_StateType.IMC)
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalHGD[Math.Min(patientIn.CountFollowUp, postIntervalHGD.Length - 1)];
}
else
{
Console.WriteLine(new System.ComponentModel.WarningException("Wrong follow-up surveillance!").Message);
}
}
}
public void PostSurgeryMortality(BE_Patient patientIn, BE_Cycle cycleIn, Random rand)
{
int yearDifference = (cycleIn.ID - patientIn.SurgeryCycle) / 4; // Assumption: Cycle length is three months.
double mortality = 0;
if (patientIn.PreSurgeryStateName == "T1a")
{
mortality = postMortalityT1a[Math.Min(yearDifference, postMortalityT1a.Length - 1)];
}
else if (patientIn.PreSurgeryStateName == "T1b")
{
mortality = postMortalityT1b[Math.Min(yearDifference, postMortalityT1b.Length - 1)];
}
else if (patientIn.PreSurgeryStateName == "SC")
{
mortality = postMortalitySC[Math.Min(yearDifference, postMortalitySC.Length - 1)];
}
else
{
Console.WriteLine(new System.ComponentModel.WarningException("Wrong PostSurgeryMortality!").Message);
}
if (rand.NextDouble() <= mortality)
{
patientIn.Die("PostSurgery");
}
}
public void PerformSurgery(BE_Patient patientIn, BE_Cycle cycleIn, Random rand)
{
patientIn.Status = BE_PatientStatus.Surgery;
patientIn.ActiveNaturalProgression = false; // When patients undergo surgery, they no longer move under natural progression probabilities.
patientIn.ActiveRecurrenceProbability = false; // When patients undergo surgery, they no longer move under recurrence probabilities.
patientIn.HasSurgery = true; // Assumption: Patient compliance is 100%.
patientIn.PreSurgeryStateName = DeterminePreSurgeryStateName(patientIn, rand); // The pre-surgery state of the patient is recorded.
patientIn.SurgeryCycle = cycleIn.ID; // The cycle in which the patient undergoes surgery is recorded.
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.Surgery);
// Cost is recorded on the patient, the surgery modality, and the cycle.
patientIn.UpdateCost(costSurgery);
this.UpdateCost(costSurgery);
cycleIn.UpdateCost(costSurgery);
// Surgery-related mortality.
double mortality = 0;
if (patientIn.ConfirmedState.Type == BE_StateType.IMC)
{
mortality = mortalityIMC;
}
else
{
mortality = mortalitySC;
}
if (rand.NextDouble() < mortality)
{
patientIn.Die("Surgery_Mortality");
return; // If the patient dies, the execution of this function is terminated.
}
// Surgery-related adverse events.
if (rand.NextDouble() <= adverseEvent.Probability)
{
patientIn.adverseEventHistory.Add(cycleIn.ID, BE_AdverseEventType.Surgery);
patientIn.UpdateCost(adverseEvent.Cost);
this.UpdateCost(adverseEvent.Cost);
cycleIn.UpdateCost(adverseEvent.Cost);
}
// Chemotherapy for some of the patients with SC.
if (patientIn.ConfirmedState.Type == BE_StateType.SC)
{
if (rand.NextDouble() <= chemotherapyRatioSC)
{
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.Chemotherapy);
patientIn.UpdateCost(costChemotherapy);
this.UpdateCost(costChemotherapy);
cycleIn.UpdateCost(costChemotherapy);
}
}
patientIn.NextTreatment = cycleIn.ID + 1; // Assumption: Patients receive postsurgery care in each cycle.
}
public void MoveNaturalProgression(BE_State[] states, BE_Cycle cycleIn, Random rand)
{
int newIndex = currentState.FindNextStateID(rand);
currentState.Population--;
currentState = states[newIndex];
stateHistory.Add(cycleIn.ID, currentState.Type);
currentState.Population++;
}
public void ScreenPatient(BE_Patient patientIn, BE_Cycle cycleIn, Random rand)
{
// Six possible outcomes: "true_positive", "false_negative", "true_negative", "false_positive", "death", and "no_show"
if (rand.NextDouble() <= adherence) // The patient comply with the screening test.
{
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.Screening);
// Cost is recorded on the patient, the screening modality, and the cycle.
patientIn.UpdateCost(cost);
this.UpdateCost(cost);
cycleIn.UpdateCost(cost);
// Screening-related mortality.
if (rand.NextDouble() <= mortality)
{
patientIn.Die("Screening_" + type.ToString());
patientIn.screenResult.Add(BE_ScreeningResult.Death);
return; // If the patient dies, the execution of this function is terminated.
}
// Screening-related adverse events.
// missing AE
if (patientIn.CurrentState.Type != BE_StateType.NoBarretts) // The patient is not in the NoBarretts state, it means the patient has the disease.
{
if (rand.NextDouble() <= sensitivity)
{
patientIn.HasPositiveTest = true;
patientIn.screenResult.Add(BE_ScreeningResult.TruePositive); // Correct diagnosis of the disease.
}
else
{
patientIn.screenResult.Add(BE_ScreeningResult.FalseNegative); // Wrong diagnosis of the disease.
}
}
else // The patient is in the NoBarretts state, it means the patient is healthy.
{
if (rand.NextDouble() <= specificity)
{
patientIn.screenResult.Add(BE_ScreeningResult.TrueNegative); // Correct diagnosis for the healthy patient.
}
else
{
patientIn.HasPositiveTest = true;
patientIn.screenResult.Add(BE_ScreeningResult.FalsePositive); // Wrong diagnosis for the healthy patient.
}
}
}
else // The patient does not comply with the screening test.
{
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.ScreeningNoShow);
patientIn.screenResult.Add(BE_ScreeningResult.NoShow);
}
}
public void PostSurgeryCare(BE_Patient patientIn, BE_Cycle cycleIn)
{
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.PostSurgery);
// Cost is recorded on the patient, the surgery modality, and the cycle.
patientIn.UpdateCost(costAnnualPostCare / 4);
this.UpdateCost(costAnnualPostCare / 4);
cycleIn.UpdateCost(costAnnualPostCare / 4);
patientIn.NextTreatment = cycleIn.ID + 1; // Assumption: Patients receive postsurgery care in each cycle.
}
public void GiveEETSession(BE_Patient patientIn, BE_Cycle cycleIn, BE_State[] statesIn, Random rand)
{
if (patientIn.CountEET == 0)
{
patientIn.Status = BE_PatientStatus.EET;
patientIn.PreEETState = patientIn.ConfirmedState;
patientIn.RealPreEETState = patientIn.CurrentState;
patientIn.ActiveNaturalProgression = false;
}
patientIn.CountEET++; // Assumption: Patient compliance is 100%.
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.EET);
// Cost is recorded on the patient, the EET modality, and the cycle.
patientIn.UpdateCost(costPerSession);
this.UpdateCost(costPerSession);
cycleIn.UpdateCost(costPerSession);
// EET-related mortality.
if (rand.NextDouble() <= mortality)
{
patientIn.Die("EET_Mortality");
return; // If the patient dies, the execution of this function is terminated.
}
// EET-related adverse events.
if (rand.NextDouble() <= adverseEvent.Probability)
{
patientIn.adverseEventHistory.Add(cycleIn.ID, BE_AdverseEventType.EET);
patientIn.UpdateCost(adverseEvent.Cost);
this.UpdateCost(adverseEvent.Cost);
cycleIn.UpdateCost(adverseEvent.Cost);
}
if (patientIn.CountEET == sessionCount)
{
int nextStateID = FindEfficacyState(patientIn.RealPreEETState.ID, rand);
patientIn.MoveEETEfficacy(statesIn[nextStateID], cycleIn);
}
else
{
patientIn.NextTreatment = cycleIn.ID + 2; // Assumption: EET sessions are held at six-month intervals.
}
}
public void SurveilPatient(BE_Patient patientIn, BE_Cycle cycleIn, Random rand)
{
if (rand.NextDouble() <= adherence) // The patient comply with surveillance.
{
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.Surveillance);
// Cost is recorded on the patient, the surveillance modality, and the cycle.
patientIn.UpdateCost(cost);
this.UpdateCost(cost);
cycleIn.UpdateCost(cost);
// Surveillance-related mortality.
if (rand.NextDouble() <= mortality)
{
patientIn.Die("Surveillance");
return; // If the patient dies, the execution of this function is terminated.
}
// Surveillance-related adverse events.
if (rand.NextDouble() <= adverseEvent.Probability)
{
patientIn.adverseEventHistory.Add(cycleIn.ID, BE_AdverseEventType.Surveillance);
patientIn.UpdateCost(adverseEvent.Cost);
this.UpdateCost(adverseEvent.Cost);
cycleIn.UpdateCost(adverseEvent.Cost);
}
if (rand.NextDouble() <= sensitivity)
{
patientIn.ConfirmedState = patientIn.CurrentState; // Correct diagnosis of the health state.
SurveillanceDecision(patientIn, cycleIn, rand);
}
else
{
patientIn.NextSurveillance = cycleIn.ID + intervalNDBE; // Assumption: In the case of misdiagnosis, it is treated as NDBE.
}
}
else
{
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.SurveillanceNoShow);
patientIn.NextSurveillance = cycleIn.ID + intervalNDBE; // Assumption: If there is no adherence, it is treated as NDBE.
}
}
public void GiveTouchUpRFA(BE_Patient patientIn, BE_Cycle cycleIn, BE_State[] statesIn, Random rand)
{
patientIn.CountRFA++; // Assumption: Patient compliance is 100 %.
if (patientIn.CountRFA == maxTouchUpRFA)
{
patientIn.CompletedMaxRFA = true;
}
patientIn.CountFollowUp = 0; // The patient's follow-up intervals are reset.
patientIn.PreEETState = patientIn.ConfirmedState;
patientIn.RealPreEETState = patientIn.CurrentState;
patientIn.ActiveNaturalProgression = false;
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.RFA);
// Cost is recorded on the patient, the EET modality, and the cycle.
patientIn.UpdateCost(costRFA);
this.UpdateCost(costRFA);
cycleIn.UpdateCost(costRFA);
// EET-related mortality.
if (rand.NextDouble() <= mortality)
{
patientIn.Die("RFA_Mortality");
return; // If the patient dies, the execution of this function is terminated.
}
// EET-related adverse events.
if (rand.NextDouble() <= adverseEvent.Probability)
{
patientIn.adverseEventHistory.Add(cycleIn.ID, BE_AdverseEventType.RFA);
patientIn.UpdateCost(adverseEvent.Cost);
this.UpdateCost(adverseEvent.Cost);
cycleIn.UpdateCost(adverseEvent.Cost);
}
int nextStateID = FindEfficacyState(patientIn.RealPreEETState.ID, rand);
patientIn.MoveEETEfficacy(statesIn[nextStateID], cycleIn);
}
public void GivePalliativeTreatment(BE_Patient patientIn, BE_Cycle cycleIn)
{
patientIn.Status = BE_PatientStatus.Palliative;
patientIn.ActiveNaturalProgression = false; // When patients receive palliative treatment, they no longer move under natural progression probabilities.
patientIn.ActiveRecurrenceProbability = false; // When patients receive palliative treatment, they no longer move under recurrence probabilities.
patientIn.UnderPalliative = true; // Assumption: Patient compliance is 100%.
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.Palliative);
// Cost is recorded on the patient, the palliative treatment modality, and the cycle.
patientIn.UpdateCost(costAnnual / 4); // Assumption: The cycle length is three months, and the palliative treatment cost is provided annually.
this.UpdateCost(costAnnual / 4);
cycleIn.UpdateCost(costAnnual / 4);
// Palliative treatment-related mortality is handled in the mortality part of the code.
patientIn.NextTreatment = cycleIn.ID + 1; // Assumption: Patients receive palliative treatment in each cycle.
}
public void MoveRecurrence(BE_EET EETIn, BE_State[] states, BE_Cycle cycleIn, Random rand)
{
if (rand.NextDouble() <= EETIn.recurrence[preEETState.ID])
{
status = BE_PatientStatus.NaturalHistory;
activeRecurrenceProbability = false;
activeNaturalProgression = true;
int newIndex = EETIn.FindRecurrenceState(preEETState.ID, rand);
currentState.Population--;
currentState = states[newIndex];
stateHistory.Add(cycleIn.ID, currentState.Type);
currentState.Population++;
}
else
{
stateHistory.Add(cycleIn.ID, currentState.Type);
}
}
public void SurveillanceDecision(BE_Patient patientIn, BE_Cycle cycleIn, Random rand) // Decides whether the patient needs treatment or when is the next surveillance cycle.
{
patientIn.Status = BE_PatientStatus.NaturalHistory;
if (patientIn.ConfirmedState.Type == BE_StateType.NDBE)
{
patientIn.NextSurveillance = cycleIn.ID + intervalNDBE;
patientIn.IsLastSurveillanceLGD = false; // two times in a row is required
}
else if (patientIn.ConfirmedState.Type == BE_StateType.LGD)
{
if (patientIn.IsLastSurveillanceLGD == false)
{
patientIn.NextSurveillance = cycleIn.ID + intervalLGD;
patientIn.IsLastSurveillanceLGD = true;
}
else
{
if (rand.NextDouble() <= persistentLGD)
{
patientIn.NextTreatment = cycleIn.ID;
}
else
{
patientIn.NextSurveillance = cycleIn.ID + intervalNDBE; // Assumption: If it is not persistent LGD, it is treated as NDBE.
patientIn.IsLastSurveillanceLGD = false;
}
}
}
else if (patientIn.ConfirmedState.Type == BE_StateType.HGD || patientIn.ConfirmedState.Type == BE_StateType.IMC || patientIn.ConfirmedState.Type == BE_StateType.SC)
{
patientIn.NextTreatment = cycleIn.ID;
}
else
{
// Shouldn't be here with since there is no natural regression to NoBarretts. But it can happen with false positives.
}
}
public void FollowUpSurveilPatient(BE_Patient patientIn, BE_Cycle cycleIn, Random rand)
{
patientIn.CountFollowUp++; // It increases whether the patient complies or not, because the follow-up intervals must be in conjunction with the guideline recommendations.
if (rand.NextDouble() <= adherence)
{
// Intervention history is added to the patient's records.
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.FollowUpSurveillance);
// Cost is recorded on the patient, the surveillance modality, and the cycle.
patientIn.UpdateCost(cost);
this.UpdateCost(cost);
cycleIn.UpdateCost(cost);
// Surveillance-related mortality.
if (rand.NextDouble() <= mortality)
{
patientIn.Die("Follow-up surveillance");
return; // If the patient dies, the execution of this function is terminated.
}
// Surveillance-related adverse events.
if (rand.NextDouble() <= adverseEvent.Probability)
{
patientIn.adverseEventHistory.Add(cycleIn.ID, BE_AdverseEventType.FollowUpSurveillance);
patientIn.UpdateCost(adverseEvent.Cost);
this.UpdateCost(adverseEvent.Cost);
cycleIn.UpdateCost(adverseEvent.Cost);
}
if (rand.NextDouble() <= sensitivity) // Correct diagnosis of the health state.
{
patientIn.ConfirmedState = patientIn.CurrentState;
FollowUpSurveillanceDecision(patientIn, cycleIn);
}
else
{
// Assumption: In the case of misdiagnosis, the follow-up intervals continue the same based on patients pre-EET state.
if (patientIn.PreEETState.Type == BE_StateType.NDBE || patientIn.PreEETState.Type == BE_StateType.LGD)
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalLGD[Math.Min(patientIn.CountFollowUp, postIntervalLGD.Length - 1)];
}
else if (patientIn.PreEETState.Type == BE_StateType.HGD || patientIn.PreEETState.Type == BE_StateType.IMC)
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalHGD[Math.Min(patientIn.CountFollowUp, postIntervalHGD.Length - 1)];
}
else
{
Console.WriteLine(new System.ComponentModel.WarningException("Wrong follow-up surveillance!").Message);
}
}
}
else
{
patientIn.interventionHistory.Add(cycleIn.ID, BE_InterventionType.FollowUpSurveillanceNoShow);
// Assumption: If there is no adherence, the follow-up intervals continue the same based on patients pre-EET state.
if (patientIn.PreEETState.Type == BE_StateType.NDBE || patientIn.PreEETState.Type == BE_StateType.LGD)
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalLGD[Math.Min(patientIn.CountFollowUp, postIntervalLGD.Length - 1)];
}
else if (patientIn.PreEETState.Type == BE_StateType.HGD || patientIn.PreEETState.Type == BE_StateType.IMC)
{
patientIn.NextSurveillance = cycleIn.ID + postIntervalHGD[Math.Min(patientIn.CountFollowUp, postIntervalHGD.Length - 1)];
}
else
{
Console.WriteLine(new System.ComponentModel.WarningException("Wrong follow-up surveillance!").Message);
}
}
}