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\begin{document}

\title{Trust but Verify: A Case of Unintended Medication Omission}



\author[1]{Andrew Bryant}%
\author[2]{Stuart Pitman}%
\author[3]{Juan Lessing}%
\affil[1]{The University of Iowa Hospitals and Clinics}%
\affil[2]{University of Iowa Hospitals and Clinics}%
\affil[3]{University of Colorado Denver School of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\begin{abstract}
An accurate medication history prevents medication errors during
transitions of care, whereas an inaccurate medication history may lead
to unnecessary tests or prolonged hospitalization. We describe the case
of a patient with chronic hypothyroidism who presented to the hospital
with severe hypothyroidism and reported strict adherence to her home
levothyroxine.%
\end{abstract}%



\sloppy


\textbf{Introduction}

An omitted, incorrectly dosed, or interacting medication may be the
cause of patient symptoms at hospital presentation. An accurate and
complete admission medication history facilitates identification of
medication-related problems on admission; however, if the list of
medications obtained during the medication history is not reliable, then
linking a patient's symptoms to a medication-related problem becomes a
more difficult task. Despite efforts by hospitals to compile reliable
medication histories, errors may occur, and the clinician should
consider a medication history error when the clinical picture and the
medication history do not align. In these cases, applying the simple
proverb ``trust but verify'' may provide the elusive piece needed to
solve a diagnostic puzzle. Here we describe an application of ``trust
but verify'' leading to the diagnosis of a patient's mystery illness.

\textbf{Case Report}

A 78-year-old woman with multiple medical comorbidities presented to the
emergency department (ED) at an academic medical center with one week of
progressive confusion and sleepiness. Her vital signs on admission were
normal. Examination revealed a somnolent elderly female, oriented only
to person. Additionally, a low-pitched coarse voice and delayed
relaxation of reflexes were present on examination.

When conducting the admission medication history, the medical intern and
senior resident accessed the list of the patient's outpatient
medications from the health system's electronic medical record (the
patient received most of her care at this hospital and its clinics) and
then interviewed the patient's daughter, who managed her mother's home
medications. Each of the patient's fourteen medication was verified with
the patient's daughter including the dose, timing, and indication. The
patient's daughter was quite familiar with detailed information
regarding the patient's medications even specific nuances such as the
importance of giving levothyroxine before breakfast.

Workup of the patient's encephalopathy revealed a markedly elevated
thyroid stimulating hormone concentration (189 mU/L, normal: 0.4-4.2
mU/L). This finding was perplexing given a normal value one month prior
with no missed levothyroxine doses in the past month according to the
patient's daughter. A free T4 of 0.4 mg/dL (normal 4.5-11.2 mg/dL)
confirmed severe, symptomatic hypothyroidism. The patient was promptly
treated with intravenous (IV) levothyroxine due to concerns of possible
compromised oral levothyroxine absorption. Further testing involving a
levothyroxine absorption test, requiring up to nine blood draws, as well
as brain imaging to evaluate for an intracranial etiology, was
considered to determine the underlying cause of the hypothyroidism in
the face of reported levothyroxine compliance. After several days of IV
levothyroxine and before initiating this intensive and costly workup, a
resident physician on the team asked the patient's daughter to bring in
all her mother's medications from home, including pill bottles and pill
organizers. To everyone's surprise---none more so than the
daughter's---levothyroxine was absent. A telephone call to the patient's
outpatient pharmacy confirmed no levothyroxine had been dispensed for
the preceding month. The daughter, involved in the care of both her
medically complex mother and father, had not realized the levothyroxine
was missing from her mother's medications. The patient's home oral
levothyroxine was then reinitiated by the medical team, and she made a
complete recovery without relapse of symptoms.

\textbf{Discussion}

Potentially preventable medication-related ED visits and hospital
admissions are unfortunately common {[}1-4{]}. From prospective
observational studies, the median prevalence rate of hospital admissions
associated with medication nonadherence is around 4\% with almost all
considered preventable {[}5{]}.

In a prospective multicenter study involving twenty-one Dutch hospitals,
12,793 unplanned hospital admissions were screened with 714 (5.6\%)
determined to be medication-related (either from harm due to adverse
effects or due to any error in the ``process of {[}medication{]}
prescribing, dispensing, or administering''). For those admissions
categorized as preventable (332/714, 46.1\%), a case-control design was
used to determine potential risk factors; and in the multivariate
analysis, nonadherence to medication regimen (odds ratio 2.3; 95\%
confidence interval 1.4-3.8), dependent living situation (3.0; 1.4-6.5),
impaired cognition (11.9; 3.9-36.3), and polypharmacy (2.7; 1.6-4.4)
defined as greater than or equal the use of five chronic medications,
were among the statistically significant determinants of
medication-related preventable admissions {[}3{]}.

Returning to our case, how might the omission of levothyroxine have been
prevented \emph{prior to admission} ? It is possible that by decreasing
the number of home medications this patient was taking (and the daughter
was subsequently responsible for) and/or having a different reminder
packaging systems (e.g., pre-filled blister packs from a pharmacy), may
have prevented this episode of nonadherence leading to hospital
admission. However, due to a scarcity of high-quality evidence and the
need for more well-designed randomized controlled trials, optimal
interventions to improve medication adherence in older adults prescribed
multiple medications remains largely unknown {[}6{]}.

How might the preadmission omission of levothyroxine have been detected
\emph{earlier in this patient's hospital encounter} ? To decrease errors
in the admission medication history due to nonadherence (i.e., recording
that a patient is taking a particular medication preadmission, when in
fact, they are not) a review of medication fill data may be helpful.
This data can be obtained by directly contacting a patient's pharmacy or
pharmacies, or by having one's institution purchase medication insurance
claims data that can be viewed electronically. In our case, obtaining
the fill history in addition to the caregiver interview and review of
institutional medication records could have revealed this patient's lack
of a recent levothyroxine refill. However, even when armed with fill
information, caution must still be exercised as even though a medication
has been filled, a patient may not be taking it or may be taking it
differently than prescribed.

Recently, a similar case of medication nonadherence masquerading as
treatment failure was reported. Jethwa et al describe a 58-year-old male
admitted to the hospital for deep vein thrombosis. Three weeks prior,
the patient had been hospitalized for pulmonary emboli and started on
apixaban, and although he described a 2-day period of nonadherence
immediately after discharge, he reported strict compliance since that
time. With his new deep vein thrombosis, treatment failure was the
leading diagnosis on the differential. However, the medical team later
consulted pharmacy to review the patient's outpatient medication fill
history and only at that time did the patient's persistent nonadherence
become clear. Adherence verification prevented mislabeling the patient
as failing apixaban and avoided warfarin therapy and bridging with a
parenteral anticoagulant {[}7{]}.

\textbf{Conclusion}

Despite the best intentions by both a thoughtful and knowledgeable
caretaker and the patient's medical team in our case, a medication error
occurred and then persisted, contributing to a longer-than-needed
hospitalization while the patient received IV levothyroxine due to a
concern of poor oral absorption. If the proposed laboratory test and
imaging-based workup had been initiated, her inpatient stay would have
been further extended. It was only when the concept of ``trust but
verify'' was applied---in this instance, asking the daughter to bring in
the patient's home medications---that the unintentional home medication
omission was discovered.

The mature clinician will often employ the paradigm of ``trust but
verify'' in other high-stakes situations, such as personally viewing
critical imaging and speaking directly with the radiologist. Questioning
an admission medication history is an inexpensive and potentially
valuable diagnostic modality. While understanding the efficiency demands
of the busy clinical climate, we propose adopting this principle in
clinical conundrums. Re-verifying a component of the admission
medication history in our case was well worth the time investment; when
in doubt ``trust but verify'' -- it may just reveal the answer.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity, and
  preventability of medication-related visits to the emergency
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\item
  Marcum ZA, Pugh MJ, Amuan ME, et al. Prevalence of potentially
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\item
  Leendertse AJ, Egberts AC, Stoker LJ, et al. Frequency of and risk
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\item
  Chan M, Nicklason F, Vial JH. Adverse drug events as a cause of
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\item
  Mongkhon P, Ashcroft DM, Scholfield CN, et al. Hospital admissions
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\item
  Cross AJ, Elliott RA, Petrie K, et al. Interventions for improving
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  8;5(5):CD012419.
\item
  Jethwa TE, Moran KM, Maniaci MJ. Medication non-adherence as a cause
  of apixaban failure in venous thromboembolism: The importance of
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\end{enumerate}

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