This month we examine a lawsuit where the physician was not found liable for the harm to the plaintiff. This may seem unusual given what you may read in the headlines, but it’s not. In the great majority of cases, at least 80%, the jury’s ultimate decision is in favor of the doctor.

In fact, most lawsuits against health care professionals never even make it to trial. Most are settled or dismissed before a juror is ever questioned, sometimes very early in the process.

While you can’t always protect yourself from being the subject of a lawsuit, you can practice in a way that minimizes the likelihood of you being found liable in that lawsuit.

Facts of the Case

The case involved a nine-year old boy, JD, who complained of a bad stomachache. His parents took him to the emergency department of the local hospital where he was admitted with severe abdominal pain and distension. The clinicians who examined JD at the hospital suspected the child was suffering from constipation. Later that evening, the child was transferred to a children’s hospital where Dr L, a gastroenterologist, served as the child’s attending physician and oversaw his care.

The child’s symptoms were non-specific but were consistent with constipation. Dr L believed that the child was suffering from extreme constipation and proceeded under that assumption by following the appropriate treatment protocol for constipation. The child’s pain levels were decreasing, which the physician took as a good sign, although the boy did vomit more than once.

Late the next day, however, the child went into hypovolemic shock and was immediately rushed to the intensive care unit where he was ultimately diagnosed with acute pancreatitis. This was just the start of the child’s issues. Unfortunately, the pancreatitis had progressed to a necrotizing form causing a plethora of other complications. The boy required multiple surgeries and was hospitalized for over 4 months. His medical expenses were well over $2 million, and that did not include future expenses.

After the child was finally released from the hospital, his parents consulted a plaintiff’s attorney who filed a lawsuit against Dr L, the gastroenterologist, but did not sue either of the hospitals that had treated JD.

The Trial

Although, as mentioned earlier, the majority of cases settle prior to trial, this was one of the exceptions. The trial lasted a total of 4 days and included testimony from 10 witnesses including 4 medical expert witnesses. The trial hinged on whether Dr L had properly treated and monitored the boy prior to his going into shock. The plaintiff argued that Dr L departed from the appropriate standard of care by failing to order tests or take other action which would have revealed the child’s pancreatitis sooner, preventing it from turning into the necrotizing type of disease.

HealthDay News — For adolescents and young adults diagnosed with ulcerative colitis (UC), the rate of discontinuation of 5-aminosalicylic acid (5-ASA) maintenance treatment is high within the first year, according to a study published online September 4 in the British Journal of General Practice.

Nishani Jayasooriya, MBBS, from St. George’s University Hospitals NHS Foundation Trust in London, and colleagues examined the rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults one year after UC diagnosis in an observational cohort study. The impact of sociodemographic and health-related risk factors was assessed.

The researchers found that 152 of 607 adolescents and young adults starting oral 5-ASA maintenance treatment discontinued within one month, and 419 discontinued within one year. Those aged 18 to 24 years had higher discontinuation than younger age groups (74 percent versus 61 and 56 percent in those aged 10 to 14 and 15 to 17 years, respectively). Compared with adolescents, young adults had lower adherence (69 vs 80% in those aged 18 to 24 vs 10 to 14 years). The likelihood of discontinuing treatment was increased for residents in deprived vs affluent postcodes (adjusted hazard ratio, 1.46). A lower likelihood of discontinuation was seen for early corticosteroid use for an acute flare (adjusted hazard ratio, 0.68).

“These findings illustrate the importance of clinicians ensuring careful follow-up within the first year when prescribing lifelong therapies for adolescents and young adults who are diagnosed with UC, particularly adolescents transitioning to young adulthood and those living in deprived areas,” the authors write.

Abstract/Full Text

HealthDay News — For pediatric Crohn disease (PCD) patients, treatment with methotrexate combined with adalimumab, but not infliximab, is associated with a reduction in treatment failure, according to a study published online March 31 in Gastroenterology.

Michael D. Kappelman, MD, MPH, from the University of North Carolina at Chapel Hill, and colleagues conducted a randomized trial involving PCD patients initiating infliximab or adalimumab who were randomly assigned to methotrexate (156 patients [110 infliximab initiators and 46 adalimumab initiators]) or placebo (141 patients [102 infliximab initiators and 39 adalimumab initiators]).

The researchers found that the time to treatment failure did not differ by study arm in the overall population. No differences were seen between the groups among infliximab initiators, while combination therapy was associated with longer time to treatment failure among adalimumab initiators. There was a trend toward lower antidrug antibodies development observed in the combination therapy arm, which was not significant. No differences were seen in patient-reported outcomes of pain interference and fatigue. More adverse events, but fewer serious adverse events, were seen in the combination therapy arm.

“Our study findings suggest strong consideration of using combination therapy for PCD patients initiating adalimumab but not infliximab,” the authors write. “Dissemination and implementation of these findings should lead to improved outcomes in this patient population, including consideration of deimplementation of combination therapy in infliximab-treated patients.”

Several authors disclosed financial ties to biopharmaceutical companies, including AbbVie, the manufacturer of adalimumab.

Abstract/Full Text (subscription or payment may be required)

HealthDay News — In a study published August 2 in the American Journal of Roentgenology, a radiomic machine learning model predicted Crohn disease diagnosis with better performance than 2 of 3 expert radiologists.

Richard X. Liu, PhD, from the University of Cincinnati College of Medicine, and colleagues developed a machine learning-based method for predicting ileal Crohn disease using radiomic features of ileal wall and mesenteric fat from noncontrast T2-weighted magnetic resonance (MR) images. Performance of the artificial intelligence (AI) model was compared to the performance of expert radiologists.

The researchers found that for 135 patients, the 3 radiologists had accuracies of 83.7, 86.7, and 88.1% for diagnosing Crohn disease, with consensus accuracy of 88.1%. There was substantial inter-radiologist agreement (κ = 0.78). The bowel core was the best-performing region of interest (area under the receiver operating characteristic curve [AUC], 0.95; accuracy, 89.6%); whole bowel fat core and whole fat had worse performance (whole bowel AUC, 0.86; fat core AUC, 0.70; whole-fat AUC, 0.73). A clinical-only model achieved an AUC of 0.85 and accuracy of 80.0%, while an ensemble model combining bowel-core radiomic and clinical models achieved AUC of 0.98 and accuracy of 93.5%. The bowel-core radiomic-only model had better accuracy than radiologist 1 and radiologist 2, but not radiologist 3 or radiologists’ consensus. The ensemble model achieved better accuracy than radiologists’ consensus.

“Deployment of a radiomic-based model using T2-weighted MR data could decrease inter-radiologist variability and increase diagnostic accuracy for pediatric Crohn disease,” the authors write.

Abstract/Full Text (subscription or payment may be required)

Aponvie (aprepitant) has been made available by Heron Therapeutics for the prevention of postoperative nausea and vomiting in adults.

Aponvie is an injectable emulsion formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist. The formulation is identical to Heron’s approved drug product Cinvanti^®, which is indicated for chemotherapy-induced nausea and vomiting.

The safety and efficacy of Aponvie were established based on adequate and well-controlled studies of a single-dose of oral aprepitant in adults. Additionally, a single 32mg dose of Aponvie was found to be bioequivalent to oral aprepitant 40mg in a phase 1 study.

Aponvie is supplied in a single-dose vial containing 32mg of aprepitant.

References

1. Heron Therapeutics announces US commercial launch of Aponvie for the management of postoperative nausea and vomiting in adults. News release. Heron Therapeutics. March 6, 2023. https://www.prnewswire.com/news-releases/heron-therapeutics-announces-us-commercial-launch-of-aponvie-for-the-management-of-postoperative-nausea-and-vomiting-in-adults-301763277.html.
2. Aponvie. Package insert. Heron Therapeutics; 2022. Accessed March 6, 2023. https://aponvie.com/prescribing-information.pdf.

The table below is a review of notable updates that occurred in April 2023 for investigational products in development (not an inclusive list). Click on the status to view our full coverage.

HealthDay News — Issues related to the assessment and management of inguinal hernias in children are discussed in a clinical report published online June 26 in Pediatrics.

Faraz A. Khan, MD, from Loma Linda University Children’s Hospital in California, and colleagues reviewed the available data and identified best practices in management of inguinal hernias in children.

The authors note that inguinal hernias are a common pediatric surgical condition; the preference for and timing of surgical repair is driven by the risk of inguinal hernia incarceration. Repair can be safely considered after discharge from the neonatal intensive care unit for preterm infants. To achieve optimal outcomes, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should repair pediatric inguinal hernias. The laparoscopic approach is gaining popularity and is as, if not more, effective than traditional open high ligation. Family values relating to the risks and benefits of each approach should be considered in the absence of strong data for or against repair of incidentally discovered patent processus vaginalis. For managing recurrent hernias, laparoscopy seems to be feasible.

No conclusive evidence is available to suggest that exposure to a single relatively short duration of anesthetic has adverse effects on neurodevelopmental outcomes in otherwise healthy children.

Abstract/Full Text

Psychological therapies, such as CBT, are recommended as a treatment for IBS; however, 60% of gastroenterologists in the United States do not have access to a psychologist who specializes in treatment approaches that focus on the link between gastrointestinal disorders and the brain. Use of digitally delivered gut-directed CBT may provide a potential solution to this clinical practice problem, if found similarly effective in terms of results.

Researchers conducted a real-world user data study from August 2021 and April 2023 to determine whether the digital mobile app, Mahana, could provide effective CBT to successfully manage IBS symptoms.

The researchers analyzed the data obtained from 699 individuals with IBS (median age, 41 years) who used the Mahana app. Approximately 195 of the 699 individuals completed 5 or more sessions/week, and 101 of these 195 individuals went on to finish the full 10 sessions/week. The remaining 504 people were nonadherent to the digital program.

The primary outcome measurement involved a calculation of the change in IBS symptom severity, which was determined using the IBS Symptom Severity Scale (IBS-SSS). Any decrease of 50 points or more was considered clinically significant. IBS-SSS was measured at baseline and repeated at weeks 5 and 10. App users also completed the Perceived Stress Scale (PSS) at baseline, week 5, and week 10.

The median IBS-SSS score of 279 at baseline indicated overall moderate severity of IBS symptoms among study participants. Irrespective of IBS subtype and other confounding factors, higher IBS-SSS scores at baseline were associated with greater response to the digital CBT program (odds ratio [OR], 1.07; 95% CI, 1.03-1.10).

At baseline, 43% of individuals with IBS self-reported anxiety and depression. Anxiety and depression (OR, 1.43; 95% CI, 1.01-2.03) as well as older age (OR, 1.12; 95% CI, 1.02-1.24) were both independently associated with adherence to the digitally delivered CBT program.

Overall IBS-SSS scores decreased by 81.5 points (P <.001) between baseline and week 5 and by 112.5 points (P <.001) between baseline and week 10. Severity of abdominal distention decreased by 9.6 points by week 5 (P <.001) and 13.4 points by week 10 (P <.001). Abdominal pain severity decreased by 11.3 points by week 5 (P <.001) and maintained a 10-point decrease at week 10 (P <.001). At both week 5 and week 10, individuals with IBS reported one less day of pain due to IBS symptoms compared with baseline (both P <.001).

“Digital health applications have the potential to democratize specialty services such as CBT and allow integrated care to scale for patients with IBS,” study authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Researchers retrospectively assessed patients diagnosed with NAFLD without portal hypertension who presented to their clinic from January 1, 2019 to October 31, 2022. Patients who had body composition testing with body impedance analysis and hepatic fibrosis and steatosis assessment by transient elastography at their initial visit were included in the analysis.

Participants’ demographic and clinical characteristics were evaluated, as were markers of steatosis and fibrosis and indices of body composition, such as percent body fat (PBF), VFA, and TFM. Univariable (UV) linear regression was used to determine the risk for fibrosis to then create a multivariate (MV) regression model to define the association between adiposity and fibrosis degree.

The analysis included 283 patients (men, 44.9%; mean [SD] age, 50.6[14.6] years; mean body mass index [BMI], 32.7[7.3] kg/m²). Of the cohort, 72 patients (25.4%) had evidence of fibrosis (≥F1), and 9% (n = 26) had advanced fibrosis (F3 or F4). Among comorbidities, 60 patients (21.2%) had diabetes and 166 (58.6%) had hyperlipidemia. BMI (odds ratio [OR] 1.1; 95% CI, 1.05-1.15; P < .001) and diabetes (OR 4.72; 95% CI, 2.50-8.89; P <.001) were risk factors for fibrosis.

In the UV analysis, PBF, VFA, and TFM were significantly associated with fibrosis. In the MV analysis after adjustment for BMI, the association with PBF was attenuated (OR, 1.05; 95% CI, 0.97-1.24; P =.205) and increased VFA (OR, 1.01; 95% CI, 1.00-1.20; P =.009) and TFM (OR, 1.07; 95% CI, 1.02-1.12; P =.004) was still significantly associated with fibrosis.

Each pound of truncal fat increased the risk for fibrosis by 6.9%, and every cubic centimeter of visceral fat increased the risk by 1.3%.

“On MV analysis, PBF was not associated with fibrosis, indicating that type and location of adiposity may be implicated in NAFLD progression, consistent with previous literature on metabolic activity of visceral fat,” the study authors wrote. “In the absence of formal body composition testing, waist circumference may serve as a surrogate for visceral adiposity, leading to improved risk stratification of patients with NAFLD.”

Edward L. Barnes, MD, MPH, from the University of North Carolina at Chapel Hill, and colleagues developed recommendations for the prevention and treatment of pouchitis and cuffitis to support practitioners in their management of these conditions.

The guideline panel made 9 conditional recommendations. The AGA suggests using antibiotics for treatment of pouchitis in patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis and experience intermittent symptoms of pouchitis. Probiotics are suggested for the prevention of recurrent pouchitis in patients who experience recurrent episodes of pouchitis that respond to antibiotics. Chronic antibiotic therapy is suggested to prevent recurrent pouchitis in patients who experience recurrent pouchitis that responds to antibiotics but relapses after stopping antibiotics; however, advanced immunosuppressive therapies approved for treatment of inflammatory bowel disease are suggested for patients who are intolerant to antibiotics or who are concerned about the risks of long-term antibiotic therapy. Advanced immunosuppressive therapies are also suggested for patients with recurrent pouchitis with inadequate response to antibiotics; corticosteroids can also be considered for these patients.

“As providers we struggle to get insurance approval for medications to treat pouchitis, because it has not been a well-defined or recognized entity,” coauthor Siddharth Singh, MD, from the University of California San Diego in La Jolla, said in a statement. “Our intention with this guideline is to help improve access for patients and providers to use these advanced therapies.”

Several authors disclosed ties to the pharmaceutical industry.

Abstract/Full Text

HealthDay News — Curcumin and omeprazole have similar efficacy for functional dyspepsia, according to a study published online September 11 in BMJ Evidence-Based Medicine.

Pradermchai Kongkam, MD, from the Chulalongkorn University Faculty of Medicine in Bangkok, and colleagues conducted a randomized trial to compare the efficacy of curcumin versus omeprazole for patient-reported outcomes among participants with a diagnosis of functional dyspepsia. Two hundred six patients were randomly assigned to one of three groups: curcumin alone (C), omeprazole alone (O), and curcumin plus omeprazole (C+O). The Severity of Dyspepsia Assessment (SODA) score was used to assess symptoms of functional dyspepsia on days 28 and 56.

The researchers found that on day 28, there were significant improvements in SODA scores in the pain, nonpain, and satisfaction categories for the C+O, C, and O groups. On day 56, these improvements were enhanced in the pain, nonpain, and satisfaction categories in all groups. There were no significant differences seen among the groups and no reports of serious adverse events.

“To the best of our knowledge, this study represents the first head-to-head comparison demonstrating the efficacy of curcumin in treating functional dyspepsia compared with omeprazole,” the authors write. “Curcumin and omeprazole were both effective for functional dyspepsia and did not appear to have a synergistic effect.”

Abstract/Full Text

Darvadstrocel is a dispersion of expanded allogeneic, adipose-derived mesenchymal stem cells. The double-blind, parallel-group, placebo-controlled, ADMIRE-CD II study (ClinicalTrials.gov Identifier: NCT03279081) enrolled 569 patients 18 years of age and older with clinically controlled, inactive or mildly active Crohn disease diagnosed at least 6 months prior to screening and the presence of complex perianal fistulas. Study participants were randomly assigned 1:1 to receive intralesional injection of darvadstrocel or placebo for 24 weeks.

Findings demonstrated that treatment with darvadstrocel did not meet the primary endpoint of combined remission at 24 weeks, defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collection(s) greater than 2cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment. 

“While we are disappointed with this outcome, we recognize that medical research for difficult-to-treat conditions such as complex CPF remains challenging,” said Chinwe Ukomadu, head of the GI & Inflammation Therapeutic Area Unit at Takeda. “We believe there are valuable lessons to learn from ADMIRE-CD II and are grateful to the patients and investigators who made this important research possible.”

Full study results will be presented at a future medical meeting.

Due to lack of substantial evidence on the safety of steroid treatment among pregnant patients with EoE, researchers evaluated the effect of active steroids on maternal and fetal outcomes in this population.

Adult patients who were pregnant and had a diagnosis of EoE between 2011 and 2022 were eligible for the study. Patients were categorized into a treatment (with steroids) or a 1:1 propensity-matched control group (no steroids). The steroids used in the study were fluticasone and budesonide. Maternal and fetal outcomes, including rates of spontaneous abortion, placenta previa, preeclampsia, and major congenital abnormalities, were compared between the 2 cohorts. Patients in both groups had similar age, gestational age, and major comorbidities, such as diabetes and hypertension.

A total of 1093 women were included in the study, of whom 257 (23.5%) were receiving steroid treatment.

Compared with patients who did not receive steroids, those who received steroids did not have significantly increased rates of spontaneous abortion (4.0% vs 5.22%; P =.522), placenta previa (4.0% vs 4.0%; P =1.00), preeclampsia (4.0% vs 4.8%; P =.663), premature delivery (4.0% vs 4.0%; P =1.00), hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (4.0% vs 4.0%; P =1.00), hyperemesis gravidarum (4.0% vs 4.0%; P =1.00), and major congenital abnormalities (6.4% vs 6.0%; P =.853).

Overall, study authors concluded, “The use of inhaled steroids in pregnant patients with EoE did not adversely affect maternal and fetal outcomes.”

Dupilumab blocks a shared receptor for interleukin (IL)-4 and IL-13, which are central drivers for inflammation in inflammatory diseases, including EoE.

The LIBERTY-EoE-TREET (ClinicalTrials.gov Identifier: NCT03633617) study enrolled patients with EoE. In 2 parts, patients received either 300 mg dupilumab (part A: n=42; part B: n=80) or placebo (part A: n=39; part B: n=79) weekly for 24 weeks. The primary outcomes were the change in the number of days with dysphagia; number of days using liquid, coughing, gagging, vomiting, or seeking medication attention to relieve dysphagia; and dysphagia-related pain. Outcomes were evaluated using the Dysphagia Symptom Questionnaire (DSQ).

At baseline, patients who received dupilumab or placebo reported a similar number of days with dysphagia over the past 14 days in both part A (mean, 9.7 vs 10.3 days; P =.388) and part B (mean, 11.2 vs 10.8 days; P =.304) as well as the number of days with any action taken to relieve dysphagia (mean, part A: 7.3 vs 8.2 days; part B: 9.5 vs 8.7 days), respectively.

After 24 weeks of treatment, the dupilumab recipients reported fewer days with dysphagia compared with placebo in part A (mean, 3.1 vs 6.3 days; P =.002) and part B (mean, 3.2 vs 6.3 days; P =.0001), respectively. Similarly, dupilumab treatment was associated with fewer days of dysphagia-relieving action compared with placebo (mean, part A: 3.6 vs 5.7 days; part B: 3.0 vs 5.3 days), respectively.

The least-squares mean difference (LSMD) in DSQ pain scores at week 24 relative to baseline were greater among the dupilumab cohort (LSMD, part A: -10.06; part B: -9.95) compared with the placebo cohort (LSMD, part A: -4.37; part B: -6.48), respectively. These changes from baseline were significantly greater in the dupilumab group compared with placebo in part A (difference, -5.69; P =.0002) and part B (difference, -3.46; P =.0053).

The limitations of this analysis included the short follow-up duration and the lack of a safety analysis.

These data indicated that dupilumab relieved symptoms of dysphagia among patients with EoE. The study authors concluded, “At week 24, participants in the dupilumab 300 mg [weekly] group experienced fewer days with dysphagia, fewer days with any action taken for dysphagia relief, and less pain associated with dysphagia, than participants in the placebo group.”

For the current study, researchers analyzed clinical outcomes from 2 phase 3 trials (LUCENT-1 and LUCENT-2; ClinicalTrials.gov Identifier: NCT03518086, NCT03524092, respectively). Researchers documented histoendoscopic responses at baseline, week 12 (induction), and week 52 (conclusion).

The study used univariable and multivariable logistic regression to identify baseline demographic and disease characteristics predictive of achieving week 12 histoendoscopic mucosal improvement (HEMI) and week 52 histoendoscopic mucosal remission (HEMR) in patients receiving treatment with mirikizumab.

HEMI and HEMR documentation involved, using endoscopic subscores (ES) = 0 or 1 for both outcomes. Researchers also set Geboes scores for HEMI and HEMR at less than or equal to 3.1 and less than or equal to 2B.0, respectively.

Researchers examined associations of histologic, endoscopic, and histoendoscopic mucosal endpoints at week 12 in the LUCENT-1 trial with clinical outcomes at week 40 in LUCENT-2. Odds ratios (ORs) were measured using data from patients (N=365) who achieved a clinical response with mirikizumab at week 12 in LUCENT-1 and were rerandomized to mirikizumab. For all outcomes, the researchers used nonresponder imputation for missing data.

Based on multivariable analyses, lower clinical baseline disease activity, no baseline immunomodulator use, no prior biologic/tofacitinib failure, and sex (female) were predictors of achieving HEMI at week 12 (P <.05). Baseline absence of corticosteroids predicted HEMR at week 52 (P <.05). Also, disease duration of 7 or more years was negatively associated with HEMR (P <.05).

Endoscopic remission at week 12 was associated with CR and CSFR at week 40 (both P <.05). Histological remission, HEMI, and HEMR at week 12 were associated with CSFR, CR, and symptomatic remission at week 40 (all P <.05).

“Early histologic, endoscopic and histoendoscopic response at the end of induction was associated with CSFR and CR at W52 [week 52],” the study authors wrote. “This is the first study with an p19–targeted anti–interleukin-23 monoclonal antibody in UC to identify baseline predictors of histoendoscopic treatment outcomes and early histoendoscopic predictors of meaningful longer-term UC outcomes.”

Scott Tenner, MD, MPH, from the State University of New York in Brooklyn, and colleagues discussed management of AP, defined as acute inflammation of the pancreas.

The authors note that AP is heterogeneous and progresses differently among patients. Most patients experience symptoms lasting a few days, but about 20% will experience complications including pancreatic necrosis and/or organ failure. To assess for biliary pancreatitis, transabdominal ultrasound is suggested for patients with AP; additional diagnostic evaluation is suggested for patients with idiopathic AP. Moderately aggressive fluid resuscitation is suggested for patients. Lactated Ringer solution is recommended over normal saline for intravenous resuscitation. In acute biliary pancreatitis without cholangitis, medical therapy is suggested over early endoscopic retrograde cholangiopancreatography. It is recommended that patients with severe AP should not receive prophylactic antibiotics. Patients with suspected infected pancreatic necrosis are not suggested to undergo fine needle aspiration. Early oral feeding (within 24 to 48 hours) is suggested for patients with mild AP as tolerated by the patient compared with the traditional nothing-by-mouth approach. Initial oral feeding with a low-fat solid diet is recommended for mild AP rather than a stepwise liquid-to-solid approach.

“Although further study is needed, the concept that urgent surgery is required in patients found to have infected necrosis is no longer valid,” the authors write.

Abstract/Full Text

The retrospective cohort study is based on data from TrinetX, a database that includes more than 79 million patients in 49 health care organizations.

Eligible participants were aged 18 years and older, had a primary diagnosis of EPI according to International Classification of Diseases-10 codes, and continued follow-up from 2016 to 2022. Patients who had a history of pancreas resection and/or PDAC before EPI diagnosis were excluded.

The EPI incidence was compared among patients with prediabetes, type 1 diabetes (T1D), and type 2 diabetes (T2D). The risk for PDAC was evaluated after 1:1 propensity score matching for tobacco use, alcohol use, and chronic pancreatitis.

The risk was expressed as adjusted odds ratios (aOR) with 95% confidence intervals. A chi-square test of independence was performed to compare demographic parameters, and P <.05 was regarded as statistically significant.

The overall population prevalence for EPI was 0.75% (n=24,080). T1D had a prevalence of 2.8% (n=90,753), and T2D had a prevalence of 15.7% (n=502,480). Diabetes and EPI were comorbid in 0.36% (n=11,348) of patients.

The patients with EPI were more likely to have prediabetes (1% vs 3%, P <.001), T1D (2% vs 11%, P <.0001), and T2D (12% vs 35%, P <.0001), compared with those without EPI, respectively. The patients with EPI also had an increased median hemoglobin A1c level (EPI, 6.85±2.2% vs non-EPI, 6.48±1.88%; P <.0001).

The risk for PDAC after propensity score matching among patients with EPI was increased in those who had diabetes (aOR, 1.53; 95% CI, 1.19-1.95; P = .0006), including T1D (aOR, 1.52; 95% CI, 1.02-2.25; P =.03) and new-onset T2D (aOR, 2.25; 95% CI, 1.33-3.8; P =.001). The patients who had EPI and diabetes for over 3 years did not have an increased risk for PDAC (aOR, 1.2; 95% CI, 0.78-1.86; P =.38).

“Patients with prediabetes and DM carry an increased risk of PDAC, and the coexistence of EPI may further enrich these cohorts, particularly patients with new-onset T2DM,” the investigators concluded. “More research is needed to better identify the highest-risk patients that could benefit from PDAC screening.”

This month we look at a case involving several health care professionals and several practice sites including a hospital, rehab, stroke clinic, and primary care physician’s office. It’s a reminder that while it’s important to act in the moment to treat an emergency situation, it is equally important to reexamine what was prescribed once the emergency situation has abated and determine whether such medication is still necessary.

Facts of the Case

The patient, Ms W, was 48 years old at the end of February when she arrived in the emergency department of her local hospital with a severe headache. She already had a complex medical history as a result of being involved in a car accident 3 years before. The car accident had caused the patient significant pain which was treated with orthopedic and chiropractic care, and a variety of medications. Ms W’s medications included duloxetine, cyclobenzaprine, sulindac, pregabalin, and warfarin (for atrial fibrillation).

At the hospital, a CT scan revealed a ruptured left intracranial aneurysm with hemorrhage, which was successfully treated surgically. While at the hospital, Ms W was started on divalproex sodium 250mg 3 times a day, which was prescribed for seizure prophylaxis and to treat agitation secondary to delirium. (Ms W’s other medications were continued.) Baseline liver function tests, including AST (aspartate aminotransferase), ALT (alanine transaminase) and bilirubin, conducted on March 23^rd were within normal range.

On March 27^th, Ms W was transferred to a rehab facility where divalproex sodium was continued at a dose of 250mg daily. Her other medications, including duloxetine, were continued. No liver function tests were performed while Ms W was at the rehab facility.

On April 13^th, Ms W was discharged from the rehab facility on multiple medications including duloxetine, divalproex sodium, trazodone, propranolol, and warfarin. She was instructed to follow up with her primary care physician on April 20^th, and the hospital’s stroke clinic on April 30^th. She was not advised to have liver function tests, or that there might be risks from the combination of divalproex sodium and duloxetine.

At her appointment with her primary care physician, Dr P, he performed prothrombin time (PT) and INR tests to check blood clotting but failed to order any liver function tests. Ms W’s INR was 1.5. Ten days later, on April 30, Ms W had her appointment with a nurse practitioner (NP) at the stroke clinic. At this appointment, Ms W’s INR reading was at 5.0. The NP adjusted the patient’s warfarin dose. No liver function tests were ordered or conducted.

Ms W began to feel ill the next day. As the week progressed, she began to suffer from confusion, lethargy, fatigue, nausea, and weakness. She called her primary care physician on May 8th, and he told her to immediately go to the emergency department. At the hospital, her blood test results were markedly abnormal. Her bilirubin was 4.9, AST was 2772, ALT was 2556 and blood ammonia 71. A CT scan revealed a spontaneous portosystemic shunt.

Ms. W was diagnosed with hepatic failure secondary to medications, most likely divalproex sodium and possibly duloxetine. She was discharged a week later, and seen weekly by her primary care physician, but she continued to deteriorate. By May 30^th, she was admitted to the hospital again where a liver biopsy revealed sub-massive hepatocellular necrosis, consistent with drug-induced etiology. Her liver failure was severe and life-threatening, and she required a liver transplant. Six months later, she was readmitted to the hospital for acute liver transplant rejection which was treated medically.

Patient Sues

After she recovered, Ms W contacted a plaintiff’s attorney and filed a medical malpractice lawsuit against the hospital, the rehab facility, the nurse practitioner in the stroke clinic, and Ms W’s primary care physician. Ms W’s attorney hired 2 medical experts to go over the records and assess Ms W’s medical treatment.

Both experts found fault with the clinicians’ treatment. The first expert found that Ms W’s care had fallen below the acceptable standard in monitoring liver function in a patient on medications that have the potential for liver toxicity, such as divalproex sodium and duloxetine. Liver function tests should have been obtained at the rehab facility, opined the expert, plus the patient should have been advised to have liver function monitoring after hospital discharge. The expert faulted the primary care physician for failing to order liver function tests when he saw the patient after she was released from the hospital on April 20.

The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Talicia^® to include a more flexible dosing regimen for the treatment of Helicobacter pylori (H. pylori) infection in adults.

Talicia may now be administered 3 times a day, taken at least 4 hours apart with food (eg, morning, mid-day, and evening), for 14 days. Previously, the dosing regimen required dosing every 8 hours with food.

The product is a fixed-dose oral capsule that combines the antibiotics rifabutin (12.5mg) and amoxicillin (250mg), and the proton pump inhibitor omeprazole (10mg). Each dose (4 capsules) of Talicia includes rifabutin 50mg, amoxicillin 1000mg and omeprazole 40mg. Talicia received FDA approval in March 2020 based on data from two phase 3 trials in H. pylori-positive adult patients complaining of epigastric pain and/or discomfort.

“Talicia is unique in that it is the only FDA-approved rifabutin-based therapy for the eradication of H. pylori,” said Dr June Almenoff, MD, PhD, RedHill’s Chief Medical Officer. “Through our successful collaboration with Certara, utilizing their Simcyp Simulator for physiologically based pharmacokinetic (PBPK) modeling, we have demonstrated therapeutic equivalence between TID and Q8H dosing, enabling us to provide what we believe is a more flexible Talicia regimen that we believe will be beneficial for the patient experience.”

Talicia is supplied in bottles containing 84 capsules.