Wednesday, September 4, 2019

Acetaminophen (APAP) - Drug-induced liver injury (DILI) – Vehicle Theraflu Nighttime Overdose – Complication of COPD - By Keith Torkelson for PCP Chester D Mojica MD

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[Dr. Schwabe]

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Dedicated to:

[Dr. Bruss]
Keith "Buster" Torkelson MS's
Liver Professor
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Name of this report

Acetaminophen (APAP) - Drug-induced liver injury (DILI) – Vehicle Theraflu Nighttime Overdose – Complication of COPD - By Keith Torkelson for PCP Chester D Mojica MD
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Metadata > Global_Health_Annual_Physical_19072201_Liver
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Acetaminophen (APAP) - Drug-induced liver injury (DILI) – Vehicle Theraflu Nighttime Overdose – Complication of COPD - By Keith Torkelson for PCP Chester D Mojica MD
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Keith E Torkelson MS - Date Chartered 9/4/19
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Abstract – Executive Summary
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Presenting Problems
This report addresses some problems that Keith “Buster” Torkelson MS is facing with regard to Chronic Obstructive Pulmonary Disease (COPD).  I particular we here at Mentalation Solutions Group (MSG) are investigating Buster’s elevated liver enzyme value As Measured By (AMB) clinical laboratory testing.  We feel it is likely that Buster is suffering a Drug-Induced Liver Injury (DILI).  The culprit drug appears to be Acetaminophen (APAP) contained in Theraflu Nighttime and other Over-The-Counter cold preparations.  The last “Cold & Flu” season Buster Over-Dosed (OD’d) on Theraflu Nighttime.  We also have a physician error to share here in this report.  Buster’s Primary Care Physician (PCP) appears to be an Over-challenged User of Health Technology (OCUHT).  For our PCP transactions this year (2019) we offer up the MSG Billy Award.
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[INSERT BILLY]

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Laboratory Support Materials
Buster’s last liver enzyme tests were run roughly on July 11, 2019.  For this round of lab testing we here at MSG were focused on Buster’s Glucose results.  They came in normal.  Only one item was flagged in the lab report.  The flag pointed to his ALT liver enzyme value.  His ALT was 52 U/L.  Quest Diagnostics preformed the work.  The Quest Normal Range (QNR) for ALT is 9-46 U/L.  Knowing this lab result Buster met up with his PCP to go over the latest panel of lab results.  His PCP said your “liver results are normal”.  Buster did not question the doctor’s interpretation of his ALT (liver) level.
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Prognosis
Using a semi-standard drug finder work sheet we eliminated some potential causes for Buster’s elevated ALT.  For the most part we find that over-ingestion of Theraflu Nighttime has a high chance of being the preparation driving up his ALT.  We calculated his AST: ALT Ratio.  The value returned was 0.65.  This ruled out cirrhosis.  The culprit drug appears to be Acetaminophen (APAP).  Acetaminophen is hepatotoxic (kills liver cells).  As long as Buster avoids Acetaminophen in any form his liver should demonstrate Plastic Resilience (PR).  In other words his liver should heal AMB normal AST and ALT lab results.  Buster has a follow up lab schedule this year.  The Prognosis is “Good”.
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Next Steps – Prudent Actions - Request 4 Funding (R4F)
Buster’s liver issue is tied intimately with his COPD problems.  The reason Buster took Theraflu was to address his COPD during the 2018-2019 season.  Try as he may Buster cannot put smoking cigarettes behind him and move ahead.  Brand New Day (BND) is Buster’s insurer.  In 2012 BND sent Buster with a full scholarship to a crisis residential treatment program for Buster’s Substance Use Issues.  We would like BND to send him to the same or similar program on a full paid scholarship.  This time we need a program that has a proven high chance at delivering long-term smoking cessation.  While we wait Buster will avoid any Acetaminophen containing OTCs.  In preparing for the next “Cold & Flu” season Buster will carefully consider avoiding his PCP in favor of using for a second time the BND Telehealth Benefit.  We cannot share this report with our PCP or Doctor In Charge (DIC) because it would be too much for him to: Process, digest, or apply.
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CLOZE with Numbers
Prior to naming us Mentalation Solutions Group (MSG) we Did Business As (DBA) Tork Reconstruction Company (TRC).  As TRC we saved and collected up Medical Records.  We have so many Medical Records that we really can’t put together whole collections under any given theme.  As MSG we are more efficient with records management than we were using our TRC systems.  We gathered three records from Buster’s history that documented his Liver Enzyme History (LEH).  We retrieved hard copies for years: 2007, 2015, and 2017.  On all three reports Buster’s AST and ALT results are normal.  This helps us rule out one of Buster’s potentially complicating medication: Clozapine.  Buster has been on Clozapine roughly since Dr. RP Singh first started the Clozapine process in November of 2006.  About the Liver Lab Testing (LLT) for July 11, 2019 Buster’s AST was normal while his ALT was slightly high.  Using the “gihep” calculator on July 24, 2019 we calculated an AST: ALT Ratio using the 2019 results at 0.65.  This value indicates that Cirrhosis of Buster’s liver is unlikely.  We believe that at least one cause of Buster’s elevated ALT is most likely Acetaminophen (APAP).  The primary vehicle that delivered APAP is Theraflu Nighttime.  In one pack of Theraflu the box indicates that there is 650mg of APAP.  In one box of Theraflu Nighttime there are six (6) packs or doses.  Buster took way too much APAP containing preparations last “Cold & Flu” season.  For follow-up testing about Buster’s liver health, only liver enzymes are warranted.  Once again the prognosis is “Good”.
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Partners
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Table - PCP – Care - Report Header
Pertains To Buster/CDM Unilateral V Partnership
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Specification
Entry
Note
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Client
Keith “Buster” Torkelson
Practitioner
Chester D Mojica MD
CDM
Specialty
Primary Care Physician
PCP
Date of Appointment
20190725-TH
The Billy Appointment
Time of Appointment
11am
Duration of Appointment
7 minutes
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Lab(s) Associated with Appointment
20190711-TH
Quest DX patient portal
MyQuest
Specific Area within Appointment
Liver Health as related to lab values
Liver Lab materials included here
Lab makes material available in time for appointment
Yes Via MyQuest
This is a 5.0 stars service
Nature of Appointment
Interim Routine Lab
IRL
Invoiced for Appointment
No
Accountability issue
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Satisfaction with this component of appointment
No
Poor bedside manner again
No satisfaction survey
Insurer
Brand New Day
Medicare Advantage Plan Medi-Medi Special Needs Plan
Wraparound Care
Was there an error with this component
Failing parity check between lab report and what the practitioner was observing
Doctor declares “Liver is OK”
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Last Reviewed: 20190830-F:
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List of Matrices, Tables, Figures, etc.
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Figure - Scan of Theraflu Nighttime
Results Up Front (RUF) – Key Labs From Jul 11, 2019
Results Up Front (RUF) - Lab History – 2007 & 2015 & 2017
Results Up Front (RUF) – Current Lab – 20190711-TH
Figure - Our Motivation – Applied Liver Studies
2019 – Matrix – AST: ALT Ratio
2019 – Table – Inter-lab Reference Range Comparison
Table - Elimination List – Diagnostic Rule Outs
Table – Elimination – Deepening the Picture - So What is Wrong?
Table – How did it go wrong? - Drug-induced liver injury (DILI)
2019 – Table – Drug Workup Sheet
FYI – Very Good Read – Tuning the Clinical “Eye”
Table – Further Testing Eliminations – Only One Warranted
Prognosis - 2019 – Table – Behaviors that may influence ALT levels
Table – Take Away - Key Words and Term Summary (n=14)
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In House Report Metadata
Reference report
GHlth_CCCHC_CDM_17100502_Physical_Report V2019 Practice
We changed our Level Of Rigor (LOR) this year (2019).  In years past we made an attempt to assess and share about full scope Health & Human Resources.  This full scope was centered about Brand New Day (BND) and its’ contractors.  Our PCP is a BND contractor.  On an annual cycle we published our findings in standalone and comprehensive reports.  Our comprehensive reports we centered about our product with call Christmas Report Card (CRC).  This standalone report centers about lab testing in relation to COPD.  We have new hopes about managing Buster’s COPD and his smoking cigarettes.
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Metadata - Associated Report
Global_Health_COPD_For_2019_20181107_Hope V2019
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Prescribed Assessments – Indicators of Satisfaction
Torkelson Pathology specializes in Social Pathologies.  Are methods are assessment driven.  Rather than work with clinical lab results and other clinical samples we focus and written assessments.  This report is pleasant break from written assessments.  We get to work with objective clinic evaluations such as lab results.  Two of the areas we address with written assessments are Consumer Satisfaction and Consumer Quality Of Life.  Buster’s PCP abandoned his Satisfaction Survey Program (SSP) several years ago.  If he still implemented his SSP we would have brought some of the findings in this report directly to Buster’s PCP.  With MSG’s prior satisfaction reports we made an effort to let our PCP find reports about him online.  For this report we decide to move ahead and not mention him by name so often.
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Figure - Scan Theraflu Nighttime
Drug-Induced Liver Injury (DILI)
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Theraflu Packaging and Notes
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Drug Facts
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Interest - Applied Liver Physiology and Patho-physiology
Problem(s) & Problem Resolution
Basically as you will see Buster tested high this year about one of his liver enzyme tests.  We have no records on file that indicated this had occurred before.  The suspect test is for Buster’s Alanine Aminotransferase (ALT) status in Buster’s blood.  Buster’s ALT isn’t all that high, yet his ALT was not normal at the time of the test.  We here at MSG eliminated several potential causes only to come to a tentative conclusion that it was the Theraflu Nighttime (contains hepatotoxic acetaminophen) Over-The-Counter (OTC) preparation that was suspect.  Buster took way too much Theraflu Nighttime this “Cold and Flu” season.  When we met with Dr. Chester D Mojica (CDM-PCP) he declared that the liver values “are normal”.  We had the labs on hand to show him yet he failed to give “Buster” an opening to comment.  Buster really wanted to know that until his liver heals should he quit the aspirin that CDM has and is prescribing.  Checking the literature the prognosis looks good if “Buster” avoids any preparations that contain Acetaminophen.  If we are correct Buster’s ALT levels are very likely to resolve.  His next ALT test is planned for later this year.  Now we will discuss “Liver” because Buster enjoys studying liver pathology.  Buster has a history of periodically being much sicker than he has for the first half of 2019.  It very likely he has Over Dosed (OD’d) on Acetaminophen containing preparations in seasons prior to 2018-2019.  He just did not have liver labs to bring it to our attention.
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Lab First Method (LFM)
Lab findings are objective.  MSG has a special interest in Behavioral Health. For years we promoted increases about clinical laboratory tests to support Behavioral Health (BH). Because there are so few proven lab tests about BH we use a myriad of written assessments to capture the consumer experience with Medicine and BH.  Below we share the key labs results as provided by Quest Diagnostics (QD) via their free patient portal.  This service QD calls MyQuest.
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Results Up Front (RUF) – Key Labs From Jul 11, 2019
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Results Up Front (RUF) – Labs From Jul 11, 2019
ALT Over Time – Time Series
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Special Topic – How is it Alanine Aminotransferase (ALT)?
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Results Up Front (RUF) – Liver Lab History – 2007 & 2015 & 2017
All values pertain to Keith “Buster” Torkelson
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Time Stamp
Lab
Test
Result
Ref Range
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20070302
UCI Med Cntr
AST Plasma
20 IU/L
8-40 IU/L
20070302
UCI Med Cntr
ALT Plasma
18 IU/L
0-60 IU/L
20150908
Quest DX
AST
15 U/L
10-35 U/L
20150908
Quest DX
ALT
12 U/L
9-46 U/L
20170717
Quest DX
AST
22 U/L
10-35 U/L
20170717
Quest DX
ALT
28 U/L
9-46 U/L
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Last Reviewed: 20190902-M: Interpretation: All within normal ranges
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Results Up Front (RUF) – Current Lab – 20190711-TH
All values pertain to Keith “Buster” Torkelson

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Time Stamp
DOW
Test
Description
QUANT
Note
Reference
Interp
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20190711
TH
AST
34 U/L
10-35 U/L
Slightly
Normal
20190711
TH
ALT
52 U/L
9-46 U/L
Slightly
High
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Last Reviewed: 20190902-M:
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Introduction
Special Topic - Clinical Patterns - Insurance Glossary Definition - IRMI.com
Clinical Patterns (CPs) might be defined as standardized medical procedures or routines for treating specific medical conditions.  “When clinical patterns become an accepted standard of care and are followed by physicians and hospitals, their exposure to claims alleging medical malpractice is generally reduced. However, the reverse is also true, so that when treatment deviates from an accepted clinical pattern, the exposure is increased.”
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Promises to Mentor
Back in 1987 Keith (not Buster yet) Torkelson was doing his graduate work on Trehalose as a cryo-protectant for poultry semen.  After preliminary research he determined that this endeavor would look super good on his application to Veterinary School.  In “industry” Keith’s primary mentor at the time was Doctor “Yan” Ghazikhanian.  Doctor Yan had several specialties with only one being Salmonella control efforts in commercial turkeys.  In the process of organizing and obtaining funding for his graduate research Keith was shopping for a department to oversee things.  Obvious choices were Epidemiology, Physics, Microbiology, and Masters’ of Preventative Veterinary Medicine (MPVM).  Keith, the dunderhead, picks the Pathology Department.  At this time the department chair was Dr. Donald Dungworth.  In Dr. D’s and Keith’s first meeting Dr. D instructs Keith to write a CV.  Dr. D instructed to come back with you CV and your elevator speech.  To shorten things: Dr. D accepted Keith and as such also became a mentor for Keith.  With the final acceptance interview Keith promised Dr. D to always work on refining his clinical “Eye”.  In addition Keith indicated an interest in MicroTech.  Keith was to contribute to developing Holographic Microscopes.  More recently Keith Doing Life As (DLA) Buster found this article by and from a local medical school.  Its’ title is: “Training the clinical eye and mind: using the arts to develop medical students' observational and pattern recognition skills”.  See Buster is not all that over the hill at age sixty (60).  His promise to Dr. D still matters.  We will hold off on MicroTech because it is out of scope.
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Dr. Donald "D" - One of Keith's Graduate School Mentors
At time chair of the UC Davis Pathology Department 
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In Veterinary School
We here at MSG will state (transparence) up front a Vaccine Adverse Event (VAE) complicated Keith’s career as a veterinary student.  When he could perform he did well.  Poor performance was associated with hospital stays.  Prior to returning to Orange County and attending school Keith’s GPA hovers near 3.4.  After saying goodbye to Davis in 1993 Keith attended local schools: Saddleback College, California State University @ Fullerton (CSUF), and Cypress College.  His overall Orange County GPA is 4.0.  Back to Vet School - In Fall quarter of 1992 (Actually Keith was really messed up) Keith took the required 13.40 units.  This “load” included three (3) units of Liver Physiology.  After the first year of Vet School Keith decided it was okay to earn in the B+ - A- range.  For the liver course he earned and “A-“.  Keith still used his office hours approach.  It is Buster's office hours' approach that helps us define good qualities about professionals and practitioners alike.  Before the first midterm we met with the liver professor Dr. Bruss.  He indicates to Keith that he is Mr. Liver Guy and he has high expectations for him.  When Keith went to pick up his final in person Dr. Bruss was irritated with Keith’s poor performance.  What follows is some liver stuff.
Introduction
Figure - Our Motivation – Applied Liver Studies from Fall Quarter 1992
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Applied Liver Physiology – UC Davis Veterinary Medicine Program
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What’s up with the “A-“?
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The Torkel Saga 2059 
Saturday, January 27, 2018
Veterinary Medicine – Liver Physiology – Exam Results (1992) for Keith E Torkelson, MS

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Exam Rigor
The lesson to be learned from this exam is how to convert the assigned points per question into a number of scored items.  For example a twenty (20) pointer would involve the following rigor.  Brainstorm roughly five (5) key points then embellished each with supporting information.  It is possible to over answer.  Looking back and remembering “Liver” helps Buster feel happier.  In the liver class Keith also performed his first surgery while in Vet School.  Just a side note: Lithium and surgery do not mix well.
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Process – Calculating an AST: ALT Ratio
How severe is Buster’s liver destruction?  Like we said earlier, Buster’s ALT is not all that high.  Yet to round things out we decided to calculate his AST: ALT ratio.  We found in the literature that seriously problematic (cirrhotic) livers have ratios over 100.  We calculated Buster’s ratio to be 0.65.
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2019 – Matrix – AST: ALT Ratio
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Time Stamp
DOW
Description
QUANT
Note
Reference
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20190711
TH
AST
34 U/L
10-35 U/L (Quest)
20190711
TH
ALT
52 U/L
9-46 U/L (Quest)
20190724
W
AST:ALT Ratio
0.65
“gihep” calculator
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Last Reviewed: 20190726-F: U/L = Units per Liter
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FYI - “gihep” calculator

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FYI - [Really cool calculator – Not Used at the Time]
AST: ALT Ratio Equation Page -  MediCalculator - ScyMed


Equation Parameters – AST: ALT Ratio
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How bad is it? - What level of AST is dangerous?
“Typically the range for normal AST is reported between 10 to 40 units per liter and ALT between 7 to 56 units per liter. Mild elevations are generally considered to be 2-3 times higher than the normal range. In some conditions, these enzymes can be severely elevated, in the 1000s range.” Jan 10, 2019
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2019 – Table – Inter-lab Reference Range Comparison

 “emedicinehealth” Reference Ranges

Liver Blood Tests - High & Normal Symptoms - Causes & Results

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Test
Quest
(U/L)
Reference
“emedicinehealth”
(U/L)
Reference
20190711
Quest Actual
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AST
10-35
10-40
34 U/L
HITVIRR
ALT
9-46
7-56
52 U/L
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AST/ALT
Ratio
“gihep”
34/52 = 0.65
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Last Reviewed: 20190724-W: HITVIRR = How is it variance in reference ranges
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AST :ALT Ratio Interpretation


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Table - Elimination List – Diagnostic Rule Outs
Exclusion of Other Diagnoses
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Feature
Position from
HX
Note
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Alcohol Complication
None since 2012
Aspirin
Unlikely
Keep taking as prescribe by doctor
Cholesterol-lowering medications
Unlikely
Rule pending Atorvastatin
Clozapine
Unlikely
Older labs help rule out Clozapine impact
Fatty Liver
Unlikely
Cirrhosis
Unlikely
AMB Ratio
Liver metabolism competition changes
Possible
Likely
Other medicines to treat psychiatric disorders
Unlikely
Lorazepam & Lithium
Older Labs help rule out both
Other OTCs with acetaminophen
(APAP)
Likely
As of May 2019 cold turkey off all OTC cold – etc. remedies
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Last Reviewed: 20190831-SAT:
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Table – Elimination – Deepening the Picture - So What is Wrong?
Clinical Course - LiverTox

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A careful history, focusing on
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Focus
Note
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Risk factors for viral hepatitis
No change over lifetime
Alcohol use
Not for more than 7 years
Weight gain
Insignificant
History of Autoimmune Disease
None
History of cardiac failure, shock, or septicemia
None
History of all drug intake, including time of starting and stopping prescription and nonprescription (over-the-counter) drugs and herbals within the previous 3 months
Nothing new except OTCs
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Last Reviewed: 20190726-F:
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Table – How did it go wrong? - Drug-induced liver injury (DILI)
As Measured By (AMB) – Blood Work 20190711-TH:
All information pertains to Keith “Buster” Torkelson MS
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Key Date
Chemical
Dosage
Function
Note
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20190308-F
Chlorpheniramine Maleate
UKN
Antihistamine
20190308-F
Phenylephrine Hydorchloride
UKN
Nasal decongestant
Multiple
Acetaminophen
(APAP)
650 mg
Pain Reliever/fever reducer
Theraflu Nighttime
UNK
Diphenhydramine HCL
25mg
Antihistamine/cough suppressant
UKN
Phenylephrine HCL
10mg
Nasal decongestant
20190321-TH
Doxycycline Hyclate
100mg
Antibiotic
20190602-SU
Fexofenadine HCL USP
180mg
Antihistamine
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Last Reviewed: 20190726-F: UKN = Unknown
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Clinical Course - LiverTox
More common causes have been ruled out (eliminated)
Substantiating Acetaminophen as a likely culprit - “In judging the likelihood of drug induced liver disease, six features are important”
2019 – Table – Drug Workup Sheet
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Feature
Note
Detail
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Name of suspect drug
Acetaminophen
(APAP)
Delivered with Theraflu Nighttime as well as other OTCs
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1
The onset after starting the drug
Time to onset
Very likely sometime after APAP exposure  and before the key lab test
2
The recovery after stopping the drug
Time to recovery
Pending next lab tests
3
The clinical pattern
Injury pattern and clinical phenotype
4
Exclusion of other causes of liver injury
Clozapine
Pretty much eliminated
5
Whether the drug is a known cause of liver injury
Yes APAP can injure liver
6
Response to re-exposure, whether inadvertent or intentional
Unlikely because we may never risk high levels of APAP intoxication again
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Last Reviewed: 20190830-F:
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FYI – Very Good Read – Tuning the Clinical “Eye”
Training the clinical eye and mind: using the arts to develop medical students' observational and pattern recognition skills.
Conclusion:
“The Interventions Studied Were Naturally Complementary And, Taken Together, Can Bring Greater Texture To The Process Of Teaching Clinical Medicine By Helping Us See A More Complete 'Picture' Of The Patient.”
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Operation(s) Manual Applied to CDM’s Practice
Next we want to address two separate statements made by BND core contracted doctors.  The first is Dr. Mojica’s (CDM) when choose to kill the patient-provider partnership approach.  “This is how we do it around here”.  The second is Dr. Rimal B Bera’s (RBB) statement: “This is how I choose to run my practice”.  In part he was justifying having caseloads so big the he really could not spend enough with his “Easy” clients.  We have been looking through some of Keith “Buster” Torkelson’s Vet Med learning materials.  The majority of the courses had cutting edge class notes.  Epidemiology and Behavior note sets we around 100 pages long.  Whereas, courses such neurology and microbiology lab had note sets around 500 pages.  In keeping it short we would prefer that both CDM and RBB provide us note sets on how they run their practices.  This we meet the transparency, partnership, and consumer-driven principles.
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[INSERT SCHWABE’S PRACTICE GUIDE]
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Table – Further Testing Eliminations – Only One Warranted
For Educational Purposes Only (FEPO)
Laboratory test results (and diagnoses to exclude):
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Test
Diagnosis
Change
RFs
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IgM anti-HAV
Hepatitis A
No
HBsAg or IgM anti-HBc or both
Hepatitis B
No
Anti-HCV or HCV RNA or both
Hepatitis C
No
Antinuclear antibody (ANA) and globulin levels
Autoimmune hepatitis
No
Ultrasound or other radiological visualization of gallbladder and biliary system and
Gallstones
Obstructive  jaundice
No
Ultrasound characterization of liver quality
Alcoholic and nonalcoholic fatty liver disease
No
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Liver Panel
To measure extent of liver repair
Decreased
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Number of these tests warranted = 1
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Last Reviewed: 20190830-F: FYI > Reference - Clinical Course - LiverTox

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Prognosis - 2019 – Table – Behaviors that may influence ALT levels
Special Topic - Reversibility
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#
Behavior
Application
Note
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1
Limit alcohol consumption
NA
Limited down to none 2012-2019
2
Lose weight
NA
At target weight
3
Quit smoking
Needed
Would like a SUD residential treatment program of 3 months
4
Get regular exercise
SoSo
5
Consider taking probiotic supplements to improve your digestive health
Periodic Adequate
Aside our probiotic inhaler idea
6
Eat a healthy diet
SoSo
Buster eats what is given him
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Last Reviewed: 20190724-W: NA = Not Applicable
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Rate of Healing - Reference
Liver Blood Tests - High & Normal Symptoms - Causes &Results


“How can I lower my ALT levels quickly?”
“The good news is that many people can lower their elevated ALT with changes in their lifestyle and exercise.”
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Summary
For the summary we here at MSG decided to list some take-away words and terms:
Table – Take Away - Key Words and Term Summary
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##
Key Term
Notes Pending
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01
Clinical Error
02
Clinical Patterns
03
Clozapine
04
Doctor In Charge
05
Drug-induced liver injury
06
Lived Experience
07
Mentor
08
MyQuest
09
Patient Portal
10
Prognosis
11
Reference Range
12
Request 4 Funding
13
Satisfaction Survey Program
14
Training the Clinical Eye and Mind
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Last Reviewed: 20190903-TU while at MHSA – MHA – Wellness Center West for Meeting
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Promotions
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One Health

A Schwabe Vision
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WorldWafers
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In Keeping with promises to Dr. Schwabe
A Keith "Buster" Torkelson Vision
OC - LINKS
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Images @ The End
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999
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