qsp/achalasia/ach_mrgsolve_model.R at main · pipetcpt/qsp

Repository navigation

History

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

361

362

363

364

365

366

367

368

369

370

371

372

373

374

375

376

377

378

379

380

381

382

383

384

385

386

387

388

389

390

391

392

393

394

395

396

397

398

399

400

401

402

403

404

405

406

# =============================================================================

# Achalasia (식도이완불능증) — QSP Model

# Disease: Primary idiopathic achalasia — Chicago Classification v4.0

# Phenotype: Impaired LES relaxation (IRP > 15 mmHg) + esophageal aperistalsis

# Pathobiology: Autoimmune (HSV-1/HLA-DQA1*0103/DQB1*0603) loss of

# inhibitory NO/VIP myenteric neurons → LES non-relaxation +

# body aperistalsis → dysphagia, regurgitation, weight loss

# Drugs modeled (PK + PD): ISDN (NO donor), Nifedipine (Cav1.2 blocker),

# Sildenafil (PDE5 inhibitor), Tadalafil (PDE5),

# Botulinum toxin A (SNAP-25 cleavage, intra-LES)

# Procedures: PD (pneumatic dilation), LHM (Heller myotomy), POEM (peroral

# endoscopic myotomy) modeled as instantaneous LES_PRESS step changes

# Scenarios (10): no Tx, ISDN, Nifedipine, Sildenafil, Tadalafil, Botox,

# PD, LHM, POEM, Combo (ISDN + Sild)

# Endpoints: Eckardt 0-12, IRP, LES residual pressure, esophageal diameter,

# TBE 5-min column, QoL, AE flags

# Calibration anchors:

# - Boeckxstaens 2011 NEJM (European Achalasia Trial PD vs LHM 86 vs 90% at 2y)

# - Werner 2019 NEJM (POEM vs LHM 83% vs 81% at 2y, Hannover)

# - Ponds 2019 JAMA (POEM vs PD 92% vs 54% at 2y)

# - Pasricha 1995 NEJM, 1996 GE (Botox pilot/RCT)

# - Triadafilopoulos 1991 Dig Dis Sci (Nifedipine SL crossover)

# - Bortolotti 2000 Gastroenterology (Sildenafil 50 mg)

# - Eckardt 1992 Gastroenterology (score validation)

# - Yadlapati 2021 Neurogastroenterol Motil (Chicago v4.0)

# - Vaezi 2020 ACG guideline; Zaninotto 2018 ISDE

# =============================================================================

library(mrgsolve)

code <- '

$PARAM @annotated

// ---------- Patient covariates -----------------------------------------------

BWT : 70 : Body weight (kg)

AGE : 50 : Age (years)

SEX : 0 : Sex (0=F, 1=M)

SUBTYPE : 2 : Chicago subtype (1=I, 2=II, 3=III)

DURATION : 3 : Disease duration (years)

SURG_OK : 1 : Surgical candidate (1=yes, 0=no)

CYP3A4 : 1 : CYP3A4 phenotype (0.5 PM, 1 EM, 2 UM)

// ---------- Isosorbide dinitrate (ISDN) — sublingual / PO --------------------

ISDN_F : 1.00 : SL bioavail (F=1 SL; F=0.22 PO)

ISDN_KA : 1.40 : SL absorption rate (1/h)

ISDN_CL : 90 : Clearance L/h (high first-pass mononitrate conversion)

ISDN_V : 90 : Volume of distribution (L) — SL

ISDN_ISMN_CL : 10 : ISMN clearance (active mononitrate proxy, L/h)

ISDN_EMAX : 0.40 : Max ΔLES tone reduction (fraction)

ISDN_EC50 : 5.0 : EC50 in plasma (mg/L) effective in LES

ISDN_HEAD_E : 0.50 : Headache potency (per mg/L)

// ---------- Nifedipine -------------------------------------------------------

NIF_F : 0.50 : SL/PO bioavailability

NIF_KA : 1.20 : Absorption rate (1/h)

NIF_CL : 30 : Clearance L/h

NIF_V : 100 : Volume of distribution (L)

NIF_EMAX : 0.35 : Max ΔLES tone reduction (fraction)

NIF_EC50 : 30 : EC50 (ng/mL)

NIF_HYPO_E : 0.40 : Postural hypotension potency

// ---------- Sildenafil -------------------------------------------------------

SIL_F : 0.41 : Oral bioavailability

SIL_KA : 1.50 : Absorption rate (1/h)

SIL_CL : 41 : Clearance L/h

SIL_V : 105 : Volume of distribution (L)

SIL_EMAX : 0.40 : Max ΔLES tone reduction

SIL_EC50 : 100 : EC50 (ng/mL)

SIL_HEAD_E : 0.30 : Headache potency

SIL_HYPO_E : 0.20 : Hypotension potency

// ---------- Tadalafil --------------------------------------------------------

TAD_F : 0.36 : Oral bioavailability

TAD_KA : 0.80 : Absorption rate (1/h)

TAD_CL : 2.5 : Clearance L/h (slow → 17 h t½)

TAD_V : 60 : Volume of distribution (L)

TAD_EMAX : 0.40 : Max ΔLES tone reduction

TAD_EC50 : 80 : EC50 (ng/mL)

// ---------- Botulinum toxin A (Botox) intra-LES injection --------------------

BOT_DOSE : 100 : Total Botox dose (U) per session

BOT_KE : 0.0040 : Effective LES decay rate (1/d) → ~6 mo duration

BOT_EMAX : 0.55 : Maximal ΔLES tone reduction (fraction)

BOT_EC50 : 25 : Local U equivalent giving half-max (units)

// ---------- Pneumatic dilation / LHM / POEM (procedural steps) ---------------

PROC_PD : 0 : Pneumatic dilation flag (one-shot at t=0+)

PROC_LHM : 0 : Laparoscopic Heller myotomy flag

PROC_POEM : 0 : POEM flag

POEM_SUB3 : 1 : POEM advantage in Type III (longer myotomy)

// Procedural ΔLES (fraction reduction, immediate but slow re-creep)

PD_DELTA : 0.45 : LES pressure reduction after PD

LHM_DELTA : 0.65 : LES pressure reduction after LHM

POEM_DELTA : 0.70 : LES pressure reduction after POEM (Type I/II)

POEM_T3_BONUS : 0.10 : Extra ΔLES with long POEM in Type III

// LES recurrence (creep back) rates (per year)

RECREEP_PD : 0.06 : Per-year LES recovery fraction after PD (high)

RECREEP_LHM : 0.015 : Per-year recovery after LHM (low)

RECREEP_POEM : 0.012 : Per-year recovery after POEM (low)

// ---------- Disease physiology baseline (untreated achalasia steady-state) ----

nNOS_BASE : 0.20 : Residual nNOS activity (fraction of normal)

VIP_BASE : 0.25 : Residual VIP tone

LES_REST : 40 : Untreated resting LES pressure (mmHg) — supranormal

IRP_BASE : 25 : Baseline IRP (mmHg)

ESO_BASE : 3.0 : Baseline esophageal diameter (cm), normal 2 cm

PERIST_BASE: 0.05 : Residual peristaltic integrity (frac of normal)

// Symptom progression (per year)

NEURON_DECAY : 0.05 : Annual fractional further inhibitory neuron loss

DIL_PROG : 0.20 : Annual diameter growth (cm) if untreated

STASIS_PROD: 200 : Daily food/saliva input (mL/d)

STASIS_KE : 0.05 : Stasis clearance (1/d) when functional emptying

// Symptom mapping (sigmoid sensitivity)

DYS_K : 0.10 : LES Δ→dysphagia mapping

REG_K : 0.40 : Dilatation→regurgitation mapping

CP_K : 0.15 : LES pressurization→chest pain (Type III heavy)

WT_K : 0.020 : Dysphagia→weight loss (kg/wk)

// AE thresholds

HA_EC50 : 0.25 : Headache severity threshold from cGMP elevation

HYPO_EC50 : 0.30 : Hypotension threshold from drug effect

// Misc

SCALE_T : 1.0 : Time scaling

$CMT @annotated

ISDN_GUT : ISDN sublingual absorption depot (mg)

ISDN_CEN : ISDN central plasma (mg)

ISMN_CEN : ISMN active metabolite (mg)

NIF_GUT : Nifedipine gut depot (mg)

NIF_CEN : Nifedipine plasma (mg)

SIL_GUT : Sildenafil gut depot (mg)

SIL_CEN : Sildenafil plasma (mg)

TAD_GUT : Tadalafil gut depot (mg)

TAD_CEN : Tadalafil plasma (mg)

BOTOX_LES : Botox local LES depot (U)

LES_PRESS : LES resting pressure (mmHg)

IRP_C : Integrated relaxation pressure (mmHg)

ESO_DIL : Esophageal diameter (cm)

ESO_STAS : Food/saliva stasis volume (mL)

PERIST : Peristaltic integrity (fraction)

DYS_S : Dysphagia (0-3, Eckardt component)

REG_S : Regurgitation (0-3)

CP_S : Chest pain (0-3)

WT_S : Weight-loss component (0-3)

TBE5 : 5-min TBE column height (cm)

QOL : Achalasia HRQoL (0-100; 100 best)

AE_HA : Drug headache severity (0-3)

AE_HYPO : Drug-induced postural hypotension (0-3)

$MAIN

double F_ISDN = ISDN_F;

double F_NIF = NIF_F;

double F_SIL = SIL_F;

double F_TAD = TAD_F;

// CYP3A4 adjustment for nifedipine/sildenafil/tadalafil

double CL_NIF = NIF_CL * CYP3A4;

double CL_SIL = SIL_CL * CYP3A4;

double CL_TAD = TAD_CL * CYP3A4;

// Initial conditions reflect untreated achalasia steady-state

LES_PRESS_0 = LES_REST;

IRP_C_0 = IRP_BASE;

ESO_DIL_0 = ESO_BASE + DIL_PROG * DURATION;

PERIST_0 = PERIST_BASE * (SUBTYPE == 3 ? 4 : 1); // some preserved in Type III

DYS_S_0 = 2.0;

REG_S_0 = (SUBTYPE == 1 || SUBTYPE == 2 ? 1.5 : 1.0);

CP_S_0 = (SUBTYPE == 3 ? 2.0 : 0.5);

WT_S_0 = 1.5;

TBE5_0 = 8.0;

QOL_0 = 45;

$ODE

// --------- Drug PK -----------------------------------------------------------

dxdt_ISDN_GUT = -ISDN_KA * ISDN_GUT;

dxdt_ISDN_CEN = ISDN_KA * ISDN_GUT * F_ISDN - (ISDN_CL/ISDN_V) * ISDN_CEN;

dxdt_ISMN_CEN = 0.5 * (ISDN_CL/ISDN_V) * ISDN_CEN - ISDN_ISMN_CL/ISDN_V * ISMN_CEN;

dxdt_NIF_GUT = -NIF_KA * NIF_GUT;

dxdt_NIF_CEN = NIF_KA * NIF_GUT * F_NIF - (CL_NIF/NIF_V) * NIF_CEN;

dxdt_SIL_GUT = -SIL_KA * SIL_GUT;

dxdt_SIL_CEN = SIL_KA * SIL_GUT * F_SIL - (CL_SIL/SIL_V) * SIL_CEN;

dxdt_TAD_GUT = -TAD_KA * TAD_GUT;

dxdt_TAD_CEN = TAD_KA * TAD_GUT * F_TAD - (CL_TAD/TAD_V) * TAD_CEN;

// Botox local LES depot, slow first-order decay

dxdt_BOTOX_LES = -BOT_KE * BOTOX_LES;

// --------- Plasma concentrations ---------------------------------------------

double Cp_ISDN = ISDN_CEN / ISDN_V * 1000.0; // mg/L (multiplied → ng/mL effectively)

double Cp_ISMN = ISMN_CEN / 200 * 1000.0;

double Cp_NIF = NIF_CEN / NIF_V * 1000.0; // ng/mL approx

double Cp_SIL = SIL_CEN / SIL_V * 1000.0;

double Cp_TAD = TAD_CEN / TAD_V * 1000.0;

// --------- Drug PD on LES tone (fractional reduction) ------------------------

double E_ISDN = ISDN_EMAX * (Cp_ISDN + 0.6 * Cp_ISMN) / (ISDN_EC50 + Cp_ISDN + 0.6 * Cp_ISMN);

double E_NIF = NIF_EMAX * Cp_NIF / (NIF_EC50 + Cp_NIF);

double E_SIL = SIL_EMAX * Cp_SIL / (SIL_EC50 + Cp_SIL);

double E_TAD = TAD_EMAX * Cp_TAD / (TAD_EC50 + Cp_TAD);

double E_BOT = BOT_EMAX * BOTOX_LES / (BOT_EC50 + BOTOX_LES);

// Combined Bliss-independent reduction in LES tone (drugs only; procedural step

// applied separately as initial LES_PRESS adjustment via $MAIN dosing logic).

double drug_red = 1.0 - (1.0-E_ISDN) * (1.0-E_NIF) * (1.0-E_SIL) * (1.0-E_TAD) * (1.0-E_BOT);

// --------- LES pressure dynamics ---------------------------------------------

// Untreated LES tone slowly climbs as more inhibitory neurons are lost

double les_baseline = LES_REST + 5.0 * NEURON_DECAY * DURATION;

// Procedural adjustment encoded by EVID-2 events in regimen; here we capture

// slow recurrence/creep back to baseline after a procedure dropped LES_PRESS.

double recreep = 0.0;

if (PROC_PD > 0.5) recreep = RECREEP_PD;

if (PROC_LHM > 0.5) recreep = RECREEP_LHM;

if (PROC_POEM > 0.5) recreep = RECREEP_POEM;

double les_target = les_baseline * (1.0 - drug_red);

dxdt_LES_PRESS = 2.0 * (les_target - LES_PRESS) // pharmacologic shift

+ recreep * (les_baseline - LES_PRESS); // post-proc creep back

// IRP tracks LES tone (slightly damped, target 0.65× LES_PRESS - 1)

double irp_target = 0.65 * LES_PRESS - 1.0;

dxdt_IRP_C = 1.5 * (irp_target - IRP_C);

// --------- Esophageal diameter and stasis ------------------------------------

double dil_rate = (LES_PRESS > 25.0 ? 0.0008 * (LES_PRESS - 25.0) : -0.001);

dxdt_ESO_DIL = dil_rate; // cm/day (slow)

double emptying_eff = 1.0 / (1.0 + exp(0.4 * (LES_PRESS - 18.0))); // sigmoid

dxdt_ESO_STAS = STASIS_PROD - STASIS_KE * (1.0 + 3.0 * emptying_eff) * ESO_STAS;

// --------- Peristaltic integrity (mostly fixed, minimal recovery) -------------

double per_target = PERIST_BASE * (SUBTYPE == 3 ? 4.0 : 1.0);

dxdt_PERIST = 0.001 * (per_target - PERIST); // essentially fixed

// --------- Symptom dynamics (Eckardt components) ------------------------------

double dys_target = 3.0 / (1.0 + exp(-DYS_K * (LES_PRESS - 15.0)));

double reg_target = 3.0 / (1.0 + exp(-REG_K * (ESO_DIL - 3.5))) +

0.5 * (ESO_STAS > 200 ? 1 : 0);

double cp_target = (SUBTYPE == 3 ? 3.0 : 1.5) /

(1.0 + exp(-CP_K * (LES_PRESS - 15.0)));

double wt_target = 3.0 / (1.0 + exp(-(dys_target - 1.5) * 1.5));

// Cap at 3 (Eckardt scale)

if (reg_target > 3.0) reg_target = 3.0;

if (cp_target > 3.0) cp_target = 3.0;

dxdt_DYS_S = 0.5 * (dys_target - DYS_S);

dxdt_REG_S = 0.5 * (reg_target - REG_S);

dxdt_CP_S = 0.5 * (cp_target - CP_S);

dxdt_WT_S = 0.3 * (wt_target - WT_S);

// TBE 5-min column tracks dilation and emptying

double tbe_target = 0.7 * ESO_DIL * (1.0 + 0.4 * emptying_eff) + 0.005 * ESO_STAS;

dxdt_TBE5 = 0.7 * (tbe_target - TBE5);

// QoL inversely linked to total Eckardt and proc-related GERD penalty

double eck_inst = DYS_S + REG_S + CP_S + WT_S;

double qol_target = 100.0 - 6.0 * eck_inst - 5.0 * (AE_HA + AE_HYPO);

if (qol_target < 0.0) qol_target = 0.0;

dxdt_QOL = 0.4 * (qol_target - QOL);

// AE dynamics — drugs cause AE proportional to plasma exposure

double ha_drive = ISDN_HEAD_E * (Cp_ISDN/100.0) + SIL_HEAD_E * (Cp_SIL/100.0);

double hypo_drive = NIF_HYPO_E * (Cp_NIF/100.0) + SIL_HYPO_E * (Cp_SIL/100.0)

+ ISDN_HEAD_E * 0.3 * (Cp_ISDN/100.0);

dxdt_AE_HA = 1.0 * (3.0 * ha_drive / (HA_EC50 + ha_drive) - AE_HA);

dxdt_AE_HYPO = 1.0 * (3.0 * hypo_drive / (HYPO_EC50 + hypo_drive) - AE_HYPO);

$TABLE

double ECKARDT = DYS_S + REG_S + CP_S + WT_S;

double CLIN_RESP = (ECKARDT <= 3.0 ? 1 : 0); // clinical remission flag

double IRP_OK = (IRP_C < 15.0 ? 1 : 0); // manometric success

double TBE_OK = (TBE5 < 5.0 ? 1 : 0); // adequate emptying

$CAPTURE Cp_ISDN Cp_NIF Cp_SIL Cp_TAD ECKARDT CLIN_RESP IRP_OK TBE_OK drug_red emptying_eff

mod_ach <- mcode("achalasia_qsp", code)

# =============================================================================

# Procedural step helper — adjusts LES_PRESS instantaneously

# =============================================================================

apply_procedure <- function(mod, proc = c("none","PD","LHM","POEM"), subtype = 2) {

proc <- match.arg(proc)

if (proc == "none") return(mod)

les_now <- as.numeric(init(mod)$LES_PRESS)

if (is.na(les_now) || les_now == 0) les_now <- mod$LES_REST

delta <- switch(proc,

PD = mod$PD_DELTA,

LHM = mod$LHM_DELTA,

POEM = mod$POEM_DELTA + ifelse(subtype == 3, mod$POEM_T3_BONUS, 0))

new_les <- les_now * (1 - delta)

mod %>% init(LES_PRESS = new_les, IRP_C = 0.65 * new_les - 1.0) %>%

param(setNames(list(1),

switch(proc, PD = "PROC_PD",

LHM = "PROC_LHM",

POEM = "PROC_POEM")))

}

# =============================================================================

# Scenario list (10 treatment arms)

# =============================================================================

scenarios <- list(

list(name = "S01_NoTx", regimen = ev(amt = 0, cmt = 1, time = 0)),

list(name = "S02_ISDN", regimen = ev(amt = 10, cmt = "ISDN_GUT", ii = 8, addl = 90 * 3, time = 0)),

list(name = "S03_Nifedipine",

regimen = ev(amt = 20, cmt = "NIF_GUT", ii = 8, addl = 90 * 3, time = 0)),

list(name = "S04_Sildenafil",

regimen = ev(amt = 50, cmt = "SIL_GUT", ii = 8, addl = 90 * 3, time = 0)),

list(name = "S05_Tadalafil",

regimen = ev(amt = 20, cmt = "TAD_GUT", ii = 24, addl = 360, time = 0)),

list(name = "S06_Botox",

regimen = ev(amt = 100, cmt = "BOTOX_LES",

ii = 24 * 180, addl = 3, time = 0)),

list(name = "S07_PneumaticDilation", proc = "PD"),

list(name = "S08_HellerMyotomy", proc = "LHM"),

list(name = "S09_POEM", proc = "POEM"),

list(name = "S10_ISDN_plus_Sildenafil",

regimen = c(ev(amt = 10, cmt = "ISDN_GUT", ii = 8, addl = 90 * 3),

ev(amt = 25, cmt = "SIL_GUT", ii = 8, addl = 90 * 3)))

)

# =============================================================================

# Simulation runner

# =============================================================================

run_scenario <- function(scn, mod = mod_ach, end_days = 720, subtype = 2) {

m <- mod %>% param(SUBTYPE = subtype)

if (!is.null(scn$proc)) {

m <- apply_procedure(m, scn$proc, subtype)

out <- mrgsim(m, end = end_days, delta = 1)

} else {

out <- mrgsim(m, events = scn$regimen, end = end_days, delta = 1)

}

as.data.frame(out) %>% transform(scenario = scn$name, subtype = subtype)

}

if (FALSE) {

# ------- Example: simulate all 10 scenarios for Type II achalasia ----------

library(dplyr); library(ggplot2)

res_all <- do.call(rbind, lapply(scenarios, run_scenario, subtype = 2))

ggplot(res_all, aes(time / 7, ECKARDT, colour = scenario)) +

geom_line(linewidth = 0.9) +

geom_hline(yintercept = 3, lty = 2) +

labs(x = "Weeks", y = "Eckardt symptom score",

title = "Achalasia QSP — Eckardt score trajectories (10 scenarios)") +

theme_minimal()

ggplot(res_all, aes(time / 30, LES_PRESS, colour = scenario)) +

geom_line(linewidth = 0.9) +

geom_hline(yintercept = c(15, 35), lty = 3) +

labs(x = "Months", y = "LES resting pressure (mmHg)") +

theme_minimal()

}

# =============================================================================

# Calibration notes (anchors with literature targets)

# =============================================================================

# 1. Resting LES pressure target ranges:

# - Healthy 10–35 mmHg; achalasia typically 35–60 mmHg

# - Post-LHM ~12 mmHg; post-POEM ~10–14 mmHg; post-PD ~15–18 mmHg

# [Eckardt 1992 GE; Boeckxstaens 2011 NEJM; Werner 2019 NEJM]

# 2. IRP target: <15 mmHg success threshold (Chicago v4.0)

# [Yadlapati 2021 NGM]

# 3. Clinical success (Eckardt ≤3) at 2 years (Boeckxstaens 2011 NEJM):

# - PD: 86% (recurrence rises after 5 y)

# - LHM: 90%

# - POEM (Werner 2019): 83% non-inferior to LHM

# - POEM > PD (Ponds 2019): 92% vs 54% @ 2 y

# 4. Botox single session: ~70% clinical response at 1 mo, dropping to

# 32% at 6 mo, 17% at 1 y (Pasricha 1996; Annese 2000)

# Re-dose mean every 6–9 months.

# 5. Nifedipine 10–20 mg SL: ↓LES pressure by 30–40% lasting 30–60 min

# (Triadafilopoulos 1991 DDS; Bortolotti 1981 GE)

# 6. Sildenafil 50 mg PO: ↓LES pressure by 35% lasting ~2 h

# (Bortolotti 2000 GE; Eherer 2002 Gut)

# 7. AE rates:

# - Nitrate headache 30–60%, hypotension 5–10%

# - Nifedipine pedal edema/flushing 15–25%

# - PDE5 headache 15–25%

# - PD perforation 1–3%

# - POEM post-procedural reflux 30–50% (PPI required)

# 8. Disease progression untreated:

# - Eckardt slow rise 0.3–0.6 pts/y; esophageal diameter +0.2 cm/y

# - End-stage sigmoid Ø > 6 cm typically after 15–20 y

# - SCC risk 16-fold (Sandler 1995)

# 9. Subtype response (Pandolfino 2008 GE; Rohof 2013 GE):

# - Type II: best response across all therapies (~96% LHM/POEM)

# - Type I: ~80% LHM/POEM

# - Type III: spastic — POEM with long myotomy preferred (~92% vs LHM 70%)

# =============================================================================

FilesExpand file tree

ach_mrgsolve_model.R

Latest commit

History

ach_mrgsolve_model.R

File metadata and controls