THE INDEPENDENT MEDICAL BUSINESS JOURNAL
Volume XXXI, No. 2
Quality improvement Deconstructing the PDCA model BY RAHUL KORANNE, MD, MBA, FACP
he U.S. health care industry is working at a breakneck pace to understand and control the drivers of the rising per capita cost of care, while improving the quality and experience of care we provide to individual patients and large populations (IHI triple aim). More recently, the medical industry has started addressing the goal of reducing burnout in health care staff as well (the expanded quadruple aim). Clinician exposure to quality improvement (QI) models is likely to increase and providers are sure to be called on to engage in these efforts. It is imperative that frontline clinicians understand the basic premise and structure of QI efforts and become familiar with them.
Off-label prescribing An increasingly common practice
One widely used QI model is the Plan-DoCheck-Adjust (PDCA) cycle, which was created by Walter Shewhart and Dr. W. Edwards Deming and became popular across the globe in the 1950s. This model consists of four steps: Quality improvement to page 184
BY JASON VARIN, PHARMD; CLHC SLFS*; AND ILO LEPPIK, MD
n 1937 the pharmaceutical manufacturer, S. E. Massengill Company, produced a sulfonamide antibacterial preparation that used diethylene glycol as a solvent. â€œElixir Sulfanilamideâ€? was believed to be responsible for over 100 deaths and many more non-fatal poisonings. The following year, the Federal Food, Drug, and Cosmetic Act (FDCA) was passed. While it has been amended many times over the years, the intent of the FDCA regarding pharmaceuticals has been to ensure the efficacy and safety of medications prior to widespread use. Off-label prescribing to page 164
rehabilitate a body, we start T owith the mind and soul. If you or someone you know needs rehabilitation after an accident, surgery, illness or stroke, we have a simple premise for you to consider: To recover physically, you need support mentally and emotionally. How positive and how determined someone is can make all the difference. We believe the most effective therapy treats your body, mind and soul. Thatâ€™s our approach. Post-acute rehabilitation services from the Good Samaritan Society are offered at multiple inpatient and outpatient locations throughout Minnesota and the Minneapolis/St. Paul area.
To make a referral or for more information, call us at (888) GSS-CARE or visit www.good-sam.com/minnesota.
The Evangelical Lutheran Good Samaritan Society provides housing and services to qualified individuals without regard to race, color, religion, gender, disability, familial status, national origin or other protected statuses according to applicable federal, state or local laws. Some services may be provided by a third party. All faiths or beliefs are welcome. ÂŠ 2015 The Evangelical Lutheran Good Samaritan Society. All rights reserved. 15-G1553
MAY 2017 MINNESOTA PHYSICIAN
MINNESOTA HEALTH CARE ROUNDTABLE
Volume XXXI, Number 2
Efficacy, Economics, and Evolution
COVER FEATURES Off-label prescribing An increasingly common practice
Quality improvement Deconstructing the PDCA model
By Jason Varin, PharmD; CLHC SLFs; and Ilo Leppik, MD
By Rahul Koranne, MD, MBA, FACP
The changing face of pharmacy
Marilyn K. Speedie, PhD, University of Minnesota College of Pharmacy
Guidelines for care transitions Addressing patients with limited resources
Gender dysphoria in children and adolescents What physicians need to know
By Jamie Feldman, MD
Telemedicine today An expanding range of applications
Thursday, November 2, 2017 • 1-4 PM
Symphony Room III, Downtown Minneapolis Hilton and Towers
By Nick Hernandez, MBA, FACHE
By Ann Fiala, RN, BSN, CPHRM, CHC
Open fetal surgery Early treatment for spina bifida
Infant brain development and autism A breakthrough in early identification
By Brad Feltis, MD, PhD
By Jed Elison, PhD
BACKGROUND AND FOCUS:
Several recent studies have reached troubling conclusions. A huge percentage of prescription medications produce little to no therapeutic benefit for many patients. In large part this relates to a drug development paradigm and medical care model centered more on treating symptoms than curing root causes. An emerging solution to this problem is the field of regenerative medicine—an approach that directly repairs or replaces damaged tissues and organs. Though initial research and development costs present significant upfront investment, the promise of better outcomes and eventual savings are impossible to ignore.
PROFESSIONAL UPDATE: WOMEN’S HEALTH Treating older female patients Common medical issues
By Amy Diede, MD
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We will define regenerative medicine and trace its development. We will explore what the pharmaceutical, device, and insurance industries are doing now with regenerative medicine and how they can work together moving forward. We will discuss the challenges that face regenerative medicine and offer potential solutions. We will look ahead so that, as we enter the third decade of the 21st century, the pace of innovation can expand in a way that is accessible, affordable, and sustainable.
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MAY 2017 MINNESOTA PHYSICIAN
It clicked when my doctor and I discussed Trulicity ÂŽ1,2
Trulicity is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy that offers unbeaten A1C reduction*, once-weekly dosing, and the Trulicity pen.1,3 If you have patients who struggle with the idea of adding an injectable, consider Trulicity as an option for the next step in their care.1,4 Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg for additional A1C reduction. *In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,3
For more information on clinical trials, see the following page.
Trulicity is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Not recommended as first-line therapy for patients inadequately controlled on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans. Prescribe only if potential benefits outweigh potential risks. Has not been studied in patients with a history of pancreatitis; consider another antidiabetic therapy. Not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Not a substitute for insulin. Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis. Not for patients with pre-existing severe gastrointestinal disease.
Select Important Safety Information WARNING: RISK OF THYROID C-CELL TUMORS In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Trulicity and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Trulicity.
Please see Important Safety Information for Trulicity, including Boxed Warning about possible thyroid tumors including thyroid cancer, on inside spread and accompanying Brief Summary of Prescribing Information. Please see Instructions for Use included with the pen.
Learn about unbeaten A1C reduction at Trulicity.com
MINNESOTA PHYSICIAN MAY 2017
Unbeaten A1C reduction* with fewer injections 1,3
*In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,3 Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg.
Trulicity vs Victoza®
Add-on to metformin (26 weeks) 8.1
Mean Baseline A1C (%)
Trulicity vs Lantus®
Trulicity vs Byetta®
Add-on to metformin and Amaryl® (52 weeks)
Add-on to metformin and Actos® (26 weeks)
Two efficacious doses available1 Mean A1C change from baseline (%)
The recommended starting dosage of Trulicity is 0.75 mg once a week
-1.6 For patients requiring additional glycemic control, the dosage may be increased to 1.5 mg once a week
Trulicity (1.5 mg)
Trulicity (0.75 mg)
Trulicity (0.75 mg)
Victoza (1.8 mg)
Trulicity (1.5 mg)
Trulicity (1.5 mg)
Byetta (10 mcg BID) Placebo
Data represent least-squares mean.
APPROXIMATE TOTAL INJECTIONS
APPROXIMATE TOTAL INJECTIONS
APPROXIMATE TOTAL INJECTIONS
Study Descriptions Compared to Victoza3
Victoza 1.8 mg QD, SC (n=300); Trulicity 1.5 mg QW, SC (n=299)
Compared to Lantus1,5 •
Lantus QD, SC (n=262); Trulicity 0.75 mg QW, SC (n=272); Trulicity 1.5 mg QW, SC (n=273)
Compared to Byetta1,6
26-week, randomized, open-label comparator phase 3b study of adult patients with type 2 diabetes treated with metformin ≥1500 mg/day
78-week, randomized, open-label comparator phase 3 study (double-blind with respect to Trulicity dose assignment) of adult patients with type 2 diabetes treated with maximally tolerated metformin (≥1500 mg/day) and Amaryl (≥4 mg/day)
Placebo (n=141); Byetta 10 mcg BID, SC (n=276); Trulicity 0.75 mg QW, SC (n=280); Trulicity 1.5 mg QW, SC (n=279)
52-week, randomized, placebo-controlled phase 3 study (open-label assignment to Byetta or blinded assignment to Trulicity or placebo) of adult patients with type 2 diabetes treated with maximally tolerated metformin (≥1500 mg/day) and Actos (up to 45 mg/day)
Primary objective was to demonstrate superiority of Trulicity 1.5 mg vs placebo on change in A1C from baseline at 26 weeks (-1.5% vs -0.5%, respectively; difference of -1.1%; 95% CI [-1.2, -0.9]; multiplicity-adjusted 1-sided alpha level of 0.025; analysis of covariance using last observation carried forward); primary objective met
Key secondary objectives of superiority of both Trulicity doses on A1C change from baseline vs Byetta were met
Primary objective was to demonstrate noninferiority of Trulicity 1.5 mg vs Victoza 1.8 mg on A1C change from baseline at 26 weeks (-1.42% vs -1.36%, respectively; difference of -0.06%; 95% CI [-0.19, 0.07]; 2-sided alpha level of 0.05 for noninferiority with 0.4% margin; mixed-model repeated measures analysis) Primary objective of noninferiority for A1C reduction was met; secondary endpoint of superiority was not met
Starting dose of Lantus was 10 units daily. Lantus titration was based on self-measured fasting plasma glucose utilizing an algorithm with a target of <100 mg/dL; 24% of patients were titrated to goal at the 52-week primary endpoint. Mean daily dose of Lantus was 29 units at the primary endpoint Primary objective was to demonstrate noninferiority of Trulicity 1.5 mg vs Lantus on A1C change from baseline at 52 weeks (-1.1% vs -0.6%, respectively; multiplicity-adjusted 1-sided alpha level of 0.025 for noninferiority with 0.4% margin; analysis of covariance using last observation carried forward); primary objective met
Please see Important Safety Information for Trulicity, including Boxed Warning about possible thyroid tumors including thyroid cancer, on the following page and accompanying Brief Summary of Prescribing Information. Please see Instructions for Use included with the pen.
MAY 2017 MINNESOTA PHYSICIAN
Important Safety Information WARNING: RISK OF THYROID C-CELL TUMORS In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Trulicity and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Trulicity. Trulicity is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to dulaglutide or any of the product components.
The most common adverse reactions (excluding hypoglycemia) reported in ≥5% of Trulicity-treated patients in placebo-controlled trials (placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg) were nausea (5.3%, 12.4%, 21.1%), diarrhea (6.7%, 8.9%,12.6%), vomiting (2.3%, 6.0%,12.7%), abdominal pain (4.9%, 6.5%, 9.4%), decreased appetite (1.6%, 4.9%, 8.6%), dyspepsia (2.3%, 4.1%, 5.8%), and fatigue (2.6%, 4.2%, 5.6%). Gastric emptying is slowed by Trulicity, which may impact absorption of concomitantly administered oral medications. Use caution when oral medications are used with Trulicity. Drug levels of oral medications with a narrow therapeutic index should be adequately monitored when concomitantly administered with Trulicity. In clinical pharmacology studies, Trulicity did not affect the absorption of the tested, orally administered medications to a clinically relevant degree. Pregnancy: Limited data with Trulicity in pregnant women are not sufﬁcient to determine a drug-associated risk for major birth defects and miscarriage. Based on animal reproduction studies, there may be risks to the fetus from exposure to dulaglutide. Use only if potential beneﬁt justiﬁes the potential risk to the fetus. Lactation: There are no data on the presence of dulaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health beneﬁts of breastfeeding should be considered along with the mother’s clinical need for Trulicity and any potential adverse effects on the breastfed infant from Trulicity or from the underlying maternal condition.
Risk of Thyroid C-cell Tumors: Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist (GLP-1 RA), have been reported in the postmarketing period; the data in these reports are insufﬁcient to establish or exclude a causal relationship between MTC and GLP-1 RA use in humans. If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated.
Pediatric Use: Safety and effectiveness of Trulicity have not been established and use is not recommended in patients less than 18 years of age.
Pancreatitis: Has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain. If pancreatitis is suspected, discontinue Trulicity promptly. Do not restart if pancreatitis is conﬁrmed. Consider other antidiabetic therapies in patients with a history of pancreatitis.
DG HCP ISI 06FEB2017
Hypoglycemia: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of the sulfonylurea or insulin to reduce the risk of hypoglycemia. Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (eg, anaphylactic reactions and angioedema) in patients treated with Trulicity. Instruct patients who experience symptoms to discontinue Trulicity and promptly seek medical advice. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist as it is unknown whether they will be predisposed to anaphylaxis with Trulicity. Renal Impairment: In patients treated with GLP-1 RAs, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In patients with renal impairment, use caution when initiating or escalating doses of Trulicity and monitor renal function in patients experiencing severe adverse gastrointestinal reactions.
Please see Brief Summary of Prescribing Information, including Boxed Warning about possible thyroid tumors including thyroid cancer, on following pages. Please see Instructions for Use included with the pen.
Trulicity® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Trulicity is available by prescription only. Actos® is a registered trademark of Takeda Pharmaceutical Company Limited. Byetta® is a registered trademark of the AstraZeneca group of companies. Amaryl® and Lantus® are registered trademarks of Sanofi-Aventis. Victoza® is a registered trademark of Novo Nordisk A/S. Other product/company names mentioned herein are the trademarks of their respective owners. References 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. 2. Trulicity [Instructions for Use]. Indianapolis, IN: Lilly USA, LLC; 2014. 3. Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial [published correction appears in Lancet. 2014;384:1348]. Lancet. 2014;384:1349-1357. 4. Polonsky WH, Hajos TR, Dain MP, Snoek FJ. Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population. Curr Med Res Opin. 2011;27(6):1169-74. doi: 10.1185/03007995.2011.573623. Epub Apr 6, 2011. 5. Giorgino F, Benroubi M, Sun JH, et al. Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care. 2015;38(12):2241-2249. 6. Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1) [published correction appears in Diabetes Care. 2014;37:2895]. Diabetes Care. 2014;37:2159-2167.
Severe Gastrointestinal Disease: Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients. Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity.
©Lilly USA, LLC 2017. All rights reserved.
MINNESOTA PHYSICIAN MAY 2017
Trulicity® (dulaglutide) Brief Summary: Consult the package insert for complete prescribing information. WARNING: RISK OF THYROID C-CELL TUMORS • In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. • Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Trulicity and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Trulicity.
Risk of Thyroid C-cell Tumors: In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. Glucagon-like peptide (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. It is unknown whether Trulicity will cause thyroid C-cell tumors, including MTC, in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. One case of MTC was reported in a patient treated with Trulicity. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. Trulicity is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of Trulicity and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Trulicity. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated. Pancreatitis: In Phase 2 and Phase 3 clinical studies, 12 (3.4 cases per 1000 patient years) pancreatitis-related adverse reactions were reported in patients exposed to Trulicity versus 3 in non-incretin comparators (2.7 cases per 1000 patient years). An analysis of adjudicated events revealed 5 cases of confirmed pancreatitis in patients exposed to Trulicity (1.4 cases per 1000 patient years) versus 1 case in non-incretin comparators (0.88 cases per 1000 patient years). After initiation of Trulicity, observe patients carefully for signs and symptoms of pancreatitis, including persistent severe abdominal pain. If pancreatitis is suspected, promptly discontinue Trulicity. If pancreatitis is confirmed, Trulicity should not be restarted. Trulicity has not been evaluated in patients with a prior history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia in this setting. Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with Trulicity. If a hypersensitivity reaction occurs, the patient should discontinue
Clinical Studies Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Pool of Placebo-controlled Trials: These data reflect exposure of 1670 patients to Trulicity and a mean duration of exposure to Trulicity of 23.8 weeks. Across the treatment arms, the mean age of patients was 56 years, 1% were 75 years or older and 53% were male. The population in these studies was 69% White, 7% Black or African American, 13% Asian; 30% were of Hispanic or Latino ethnicity. At baseline, the population had diabetes for an average of 8.0 years and had a mean HbA1c of 8.0%. At baseline, 2.5% of the population reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR ≥60mL/min/1.73 m2) in 96.0% of the pooled study populations. Adverse Reactions in Placebo-Controlled Trials Reported in ≥5% of Trulicity-Treated Patients: Placebo (N=568), Trulicity 0.75mg (N=836), Trulicity 1.5 mg (N=834) (listed as placebo, 0.75 mg, 1.5 mg): nausea (5.3%, 12.4%, 21.1%), diarrheaa (6.7%, 8.9%, 12.6%), vomitingb (2.3%, 6.0%, 12.7%), abdominal painc (4.9%, 6.5%, 9.4%), decreased appetite (1.6%, 4.9%, 8.6%), dyspepsia (2.3%, 4.1%, 5.8%), fatigued (2.6%, 4.2%, 5.6%). (a Includes diarrhea, fecal volume increased, frequent bowel movements. b Includes retching, vomiting, vomiting projectile. c Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, gastrointestinal pain. d Includes fatigue, asthenia, malaise.) Note: Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction. Gastrointestinal Adverse Reactions: In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving Trulicity than placebo (placebo 21.3%, 0.75 mg 31.6%, 1.5 mg 41.0%). More patients receiving Trulicity 0.75 mg (1.3%) and Trulicity 1.5 mg (3.5%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.2%). Investigators graded the severity of gastrointestinal adverse reactions occurring on 0.75 mg and 1.5 mg of Trulicity as “mild” in 58% and 48% of cases, respectively, “moderate” in 35% and 42% of cases, respectively, or “severe” in 7% and 11% of cases, respectively. In addition to the adverse reactions ≥5% listed above, the following adverse reactions were reported more frequently in Trulicity-treated patients than placebo (frequencies listed, respectively, as: placebo; 0.75 mg; 1.5 mg): constipation (0.7%; 3.9%; 3.7%), flatulence (1.4%; 1.4%; 3.4%), abdominal distension (0.7%; 2.9%; 2.3%), gastroesophageal reflux disease (0.5%; 1.7%; 2.0%), and eructation (0.2%; 0.6%; 1.6%). Pool of Placebo- and Active-Controlled Trials: The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 6 placebo- and active-controlled trials evaluating the use of Trulicity as monotherapy and add-on therapy to oral medications or insulin. In this pool, a total of 3342 patients with type 2 diabetes were treated with Trulicity for a mean duration 52 weeks. The mean age of patients was 56 years, 2% were 75 years or older and 51% were male. The population in these studies was 71% White, 7% Black or African American, 11% Asian; 32% were of Hispanic or Latino ethnicity. At baseline, the population had diabetes for an average of 8.2 years and had a mean HbA1c of 7.6-8.5%. At baseline, 5.2% of the population reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR ≥60 ml/min/1.73 m2) in 95.7% of the Trulicity population. In the pool of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed as ≥5% above. Other Adverse Reactions: Hypoglycemia: Incidence (%) of Documented Symptomatic (≤70 mg/dL Glucose Threshold) and Severe Hypoglycemia in Placebo-Controlled Trials: Add-on to Metformin at 26 weeks, Placebo (N=177), Trulicity 0.75 mg (N=302), Trulicity 1.5 mg (N=304), Documented symptomatic: Placebo: 1.1%, 0.75 mg: 2.6%, 1.5 mg: 5.6%; Severe: all 0. Add-on to Metformin + Pioglitazone at 26 weeks, Placebo (N=141), Trulicity 0.75 mg (N=280), Trulicity 1.5 mg (N=279), Documented symptomatic: Placebo: 1.4%, 0.75 mg: 4.6%, 1.5 mg: 5.0%; Severe: all 0. Add-on to Glimepiride at 24 weeks, Placebo (N=60), Trulicity 1.5 mg (N=239), Documented symptomatic: Placebo: 1.7%, 1.5 mg: 11.3%; Severe: all 0. Add-on to Insulin Glargine with or without Metformin at 28 weeks, Placebo (N=150), Trulicity 1.5 mg (N=150), Documented symptomatic: Placebo: 30.0% 1.5 mg: 35.3%; Severe: Placebo: 0% 1.5 mg: 0.7%. Hypoglycemia was more frequent when Trulicity was used in combination with a sulfonylurea or insulin. In a 78-week clinical trial documented symptomatic hypoglycemia occurred in 39% and 40% of patients when Trulicity 0.75 mg and 1.5 mg, respectively, was co-administered with a sulfonylurea. Severe hypoglycemia occurred in 0% and 0.7% of patients when Trulicity 0.75 mg and 1.5 mg, respectively, was co-administered with a sulfonylurea. Documented
INDICATIONS AND USAGE Trulicity® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans. Prescribe Trulicity only to patients for whom the potential benefits outweigh the potential risk. Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. It is not a substitute for insulin. Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis. Not recommended in patients with pre-existing severe gastrointestinal disease. CONTRAINDICATIONS Do not use in patients with a personal or family history of MTC or in patients with MEN 2. Do not use in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components. WARNINGS AND PRECAUTIONS
Trulicity and other suspected medications and promptly seek medical advice. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with Trulicity. Renal Impairment: In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Because these reactions may worsen renal failure, use caution when initiating or escalating doses of Trulicity in patients with renal impairment. Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions. Severe Gastrointestinal Disease: Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients. Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity.
DG HCP BS 10FEB2017 7 x 9.5
DG HCP BS 10FEB2017 7 x 9.5
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symptomatic hypoglycemia occurred in 85% and 80% of patients when Trulicity 0.75 mg and 1.5 mg, respectively, was co-administered with prandial insulin. Severe hypoglycemia occurred in 2.4% and 3.4% of patients when Trulicity 0.75 mg, and 1.5 mg, respectively, was co-administered with prandial insulin. Heart Rate Increase and Tachycardia Related Adverse Reactions: Trulicity 0.75 mg and 1.5 mg resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm). The long-term clinical effects of the increase in HR have not been established. Adverse reactions of sinus tachycardia were reported more frequently in patients exposed to Trulicity. Sinus tachycardia was reported in 3.0%, 2.8%, and 5.6% of patients treated with placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg, respectively. Persistence of sinus tachycardia (reported at more than 2 visits) was reported in 0.2%, 0.4%, and 1.6% of patients treated with placebo, Trulicity 0.75 mg and Trulicity 1.5 mg, respectively. Episodes of sinus tachycardia, associated with a concomitant increase from baseline in heart rate of ≥15 beats per minute, were reported in 0.7%, 1.3%, and 2.2% of patients treated with placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg, respectively. Immunogenicity: Across four Phase 2 and five Phase 3 clinical studies, 64 (1.6%) Trulicitytreated patients developed anti-drug antibodies (ADAs) to the active ingredient in Trulicity (ie, dulaglutide). Of the 64 dulaglutide-treated patients that developed dulaglutide ADAs, 34 patients (0.9% of the overall population) had dulaglutide-neutralizing antibodies, and 36 patients (0.9% of the overall population) developed antibodies against native GLP-1. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to dulaglutide cannot be directly compared with the incidence of antibodies of other products. Hypersensitivity: Systemic hypersensitivity adverse reactions sometimes severe (eg, severe urticaria, systemic rash, facial edema, lip swelling) occurred in 0.5% of patients on Trulicity in the four Phase 2 and Phase 3 studies. Injection-site Reactions: In the placebo-controlled studies, injection-site reactions (eg, injection-site rash, erythema) were reported in 0.5% of Trulicity-treated patients and in 0.0% of placebo-treated patients. PR Interval Prolongation and Adverse Reactions of First Degree Atrioventricular (AV) Block: A mean increase from baseline in PR interval of 2-3 milliseconds was observed in Trulicity-treated patients in contrast to a mean decrease of 0.9 millisecond in placebo-treated patients. The adverse reaction of first degree AV block occurred more frequently in patients treated with Trulicity than placebo (0.9%, 1.7%, and 2.3% for placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg, respectively). On electrocardiograms, a PR interval increase to at least 220 milliseconds was observed in 0.7%, 2.5%, and 3.2% of patients treated with placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg, respectively. Amylase and Lipase Increase: Patients exposed to Trulicity had mean increases from baseline in lipase and/or pancreatic amylase of 14% to 20%, while placebotreated patients had mean increases of up to 3%. Postmarketing Experience: Anaphylactic reactions have been reported during post-approval use of Trulicity. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. DRUG INTERACTIONS Trulicity slows gastric emptying and thus has the potential to reduce the rate of absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with Trulicity. Drug levels of oral medications with a narrow therapeutic index should be adequately monitored when concomitantly administered with Trulicity. In clinical pharmacology studies, Trulicity did not affect the absorption of the tested, orally administered medications to any clinically relevant degree. USE IN SPECIFIC POPULATIONS Pregnancy: Risk Summary Limited data with Trulicity in pregnant women are not sufficient to determine a drug associated risk for major birth defects and miscarriage. Based on animal reproduction studies, there may be risks to the fetus from exposure to dulaglutide during pregnancy. Trulicity should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In pregnant rats administered dulaglutide during organogenesis, early embryonic deaths, fetal growth reductions, and fetal abnormalities occurred at systemic exposures at least 14-times human exposure at the maximum recommended human dose (MRHD) of 1.5 mg/week. In pregnant rabbits administered dulaglutide during organogenesis, major fetal abnormalities occurred at 13-times human exposure at the MRHD. Adverse embryo/fetal effects in animals occurred in association with decreased maternal weight and food consumption attributed to the pharmacology of dulaglutide. Lactation: Risk Summary There are no data on the presence of dulaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Trulicity and any potential adverse effects on the breastfed infant from Trulicity or from the underlying maternal condition. Pediatric Use: Safety and effectiveness of Trulicity have not been established in pediatric patients. Trulicity is not recommended for use in pediatric patients younger than 18 years. Geriatric Use: In the pool of placebo- and active-controlled trials, 620 (18.6%) Trulicity-treated patients were 65 years of age and over and 65 Trulicity-treated patients (1.9%) were 75 years of age and over. No overall differences in safety or efficacy were detected between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Hepatic Impairment: There is limited clinical experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Trulicity should be used with caution in these patient populations. In a clinical pharmacology study in subjects with Trulicity® (dulaglutide)
DG HCP BS 10FEB2017 7 x 9.5
varying degrees of hepatic impairment, no clinically relevant change in dulaglutide pharmacokinetics (PK) was observed. Renal Impairment: In the four Phase 2 and five Phase 3 randomized clinical studies, at baseline, 50 (1.2%) Trulicity-treated patients had mild renal impairment (eGFR ≥60 but <90 mL/min/1.73 m2), 171 (4.3%) Trulicity-treated patients had moderate renal impairment (eGFR ≥30 but <60 mL/min/1.73 m2) and no Trulicity-treated patients had severe renal impairment (eGFR <30 mL/min/1.73 m2). No overall differences in safety or effectiveness were observed relative to patients with normal renal function, though conclusions are limited due to small numbers. In a clinical pharmacology study in subjects with renal impairment including end-stage renal disease (ESRD), no clinically relevant change in dulaglutide PK was observed. There is limited clinical experience in patients with severe renal impairment or ESRD. Trulicity should be used with caution, and if these patients experience adverse gastrointestinal side effects, renal function should be closely monitored. Gastroparesis: Dulaglutide slows gastric emptying. Trulicity has not been studied in patients with pre-existing gastroparesis. OVERDOSAGE Overdoses have been reported in clinical studies. Effects associated with these overdoses were primarily mild or moderate gastrointestinal events (eg, nausea, vomiting) and non-severe hypoglycemia. In the event of overdose, appropriate supportive care (including frequent plasma glucose monitoring) should be initiated according to the patient’s clinical signs and symptoms. PATIENT COUNSELING INFORMATION See FDA-approved Medication Guide • Inform patients that Trulicity causes benign and malignant thyroid C-cell tumors in rats and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (eg, a lump in the neck, persistent hoarseness, dysphagia, or dyspnea) to their physician. • Inform patients that persistent severe abdominal pain, that may radiate to the back and which may (or may not) be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to discontinue Trulicity promptly, and to contact their physician, if persistent severe abdominal pain occurs. • The risk of hypoglycemia may be increased when Trulicity is used in combination with a medicine that can cause hypoglycemia, such as a sulfonylurea or insulin. Review and reinforce instructions for hypoglycemia management when initiating Trulicity therapy, particularly when concomitantly administered with a sulfonylurea or insulin. • Patients treated with Trulicity should be advised of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Inform patients treated with Trulicity of the potential risk for worsening renal function and explain the associated signs and symptoms of renal impairment, as well as the possibility of dialysis as a medical intervention if renal failure occurs. • Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of Trulicity and other GLP-1 receptor agonists. If symptoms of hypersensitivity reactions occur, patients must stop taking Trulicity and seek medical advice promptly. • Advise patients to inform their healthcare provider if they are pregnant or intend to become pregnant. • Prior to initiation of Trulicity, train patients on proper injection technique to ensure a full dose is delivered. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations. • Inform patients of the potential risks and benefits of Trulicity and of alternative modes of therapy. Inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and HbA1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and advise patients to seek medical advice promptly. • Each weekly dose of Trulicity can be administered at any time of day, with or without food. The day of once-weekly administration can be changed if necessary, as long as the last dose was administered 3 or more days before. If a dose is missed and there are at least 3 days (72 hours) until the next scheduled dose, it should be administered as soon as possible. Thereafter, patients can resume their usual once-weekly dosing schedule. If a dose is missed and the next regularly scheduled dose is due in 1 or 2 days, the patient should not administer the missed dose and instead resume Trulicity with the next regularly scheduled dose. • Advise patients treated with Trulicity of the potential risk of gastrointestinal side effects. • Instruct patients to read the Medication Guide and the Instructions for Use before starting Trulicity therapy and review them each time the prescription is refilled. • Instruct patients to inform their doctor or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens. • Inform patients that response to all diabetic therapies should be monitored by periodic measurements of blood glucose and HbA1c levels, with a goal of decreasing these levels towards the normal range. HbA1c is especially useful for evaluating long-term glycemic control.
Eli Lilly and Company, Indianapolis, IN 46285, USA US License Number 1891 Copyright © 2014, 2015, Eli Lilly and Company. All rights reserved. Additional information can be found at www.trulicity.com DG HCP BS 10FEB2017 Trulicity® (dulaglutide)
DG HCP BS 10FEB2017 7 x 9.5 MINNESOTA PHYSICIAN MAY 2017
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Second Opinions Valuable for Many Patients As many as 88 percent of patients who visit Mayo Clinic for a second opinion or diagnosis confirmation before treatment for a complex condition leave with a new or refined diagnosis, according to results of a Mayo Clinic study. Only 12 percent receive confirmation that the original diagnosis was complete and correct. Researchers examined records for 286 patients who were referred by primary care providers to Mayo Clinic’s General Internal Medicine Division in Rochester over a two-year period from Jan. 1, 2009 to Dec. 31, 2010. They compared the referring diagnosis to the final diagnosis to determine the level of consistency between the two and to find the level of diagnosis error. The diagnosis was completely changed in 21 percent of the cases and 66 percent of patients received a refined or redefined diagnosis. According to Mayo Clinic, obstacles to patients receiving second opinions may include health insurers limiting access to care outside their network to manage costs; primary
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care providers being more confident in their diagnostic expertise than was warranted in particular cases; and patients lacking the knowledge or assertiveness to request a referral. “This may prevent identification of diagnostic error, and could lead to treatment delays, complications leading to more costly treatments, or even patient harm or death,” said James Naessens, ScD, a health care policy researcher in the Division of Health Care Policy and Research and the Center for the Science of Health Care Delivery at Mayo Clinic. “We want to encourage second opinions when the provider is not certain.” The researchers also identified costs associated with second opinions. “Total diagnostic costs for cases resulting in a different final diagnosis were significantly higher than those for confirmed or redefined diagnoses, but the alternative could be deadly,” Naessens said. The team plans to conduct further research on diagnostic errors and hopes to identify ways to improve the process. “Referrals to advanced specialty care for undifferentiated problems are an essential component of patient care,” said Naessens.
“Without adequate resources to handle undifferentiated diagnoses, a potential unintended consequence is misdiagnosis, resulting in treatment delays and complications, and leading to more costly treatments.”
Allina Chosen for CMS Accountable Health Communities Project The Centers for Medicare & Medicaid Services (CMS) has chosen Allina Health to participate in a fiveyear Accountable Health Community model test to determine if bridging the gap between clinical and community services providers for patients with health-related social needs can improve the health of patients and reduce the cost of care. Allina is one of 32 organizations across the U.S. selected to participate in the project. The target area for Allina’s role in the project is Anoka, Dakota, Isanti, Ramsey, and Washington Counties. “Our role is to screen the Medicare and Medicaid patients we see in our hospitals, primary care clinics, and urgent care centers in the five-county
target area, to determine health-related social needs, and then help people to connect to community resources to address their needs,” said Ellie Zuehlke, director of community benefit and engagement at Allina Health. “We know that health-related social needs are critical drivers of unnecessary health care utilization and costs, but are often difficult to address. Our goal is to provide the link between our patients and the community services that can help them before they end up in a hospital emergency room.” The model will test whether identifying and addressing health-related social needs impacts total health care costs and reduces inpatient and outpatient utilization. Participants will implement and test one of two service delivery approaches—the assistance track, which provides community services navigation services to assist high-risk beneficiaries with accessing services to address identified health-related social needs; and the alignment track, which encourages partner alignment to ensure that community services are available and responsive to the needs of beneficiaries. Allina is participating in the assistance track.
Children’s Celebrates Safety Milestone Children’s Hospitals and Clinics of Minnesota has gone two years without a central-line associated bloodstream infection (CLABSI) in
HealthPartners Recognized for Hepatitis C Program The Pharmacy Benefit Management Institute has selected HealthPartners as one of six organizations in the U.S. to receive its Excellence Award in care management strategies. HealthPartners received the award for its medication optimization program that has helped improve care for patients who have Hepatitis C. HealthPartners’ medication optimization team works to make sure the new and improved, but very expensive, Hepatitis C medications are used. The goals of this program are to address and remove any barriers to adherence and provide support with coordination of care to ensure the best possible treatment result and lower health care costs. The team includes pharmacy navigators and medication therapy management pharmacists who work together to make sure patients are on the right medication for them and that they take it correctly with no gaps in care. The services sometimes include helping patients find the help they need to pay for their medications. Members work with the same pharmacy navigator throughout their treatment to make sure their care plans are followed. The program has resulted in nearly all patients with Hepatitis C following their prescribed medication routine and achieving cures. In 2015, HealthPartners saw a 98 percent completion rate, compared to
Ph ys St. Mary’s Medical Center is expanding its transcatheter aortic valve replacement (TAVR) program, a minimally invasive procedure used in place of open-heart surgery to replace the aortic valve. Traditionally, open-heart surgery has been the standard procedure for aortic valve replacement in intermediate risk patients. About one-third of patients who are referred for open heart surgery for aortic valve replacement are in the intermediate-risk category, which means they have a greater than 3 percent risk of dying within 30 days following surgery. “Risk for open heart surgery is determined by a multidisciplinary group,” said Dr. Jason Schultz, an interventional cardiologist who directs the TAVR program at Essentia Health-St. Mary’s Medical Center. “Previously, TAVR was approved for only high-risk patients who were not good operative candidates.” The expansion follows a 2016 Food and Drug Administration announcement that it would allow this procedure as an option for intermediate-risk patients after a clinical study showed a reasonable assurance of patient safety and effectiveness. “While surgery remains an option for intermediate-risk patients, the trial data suggests outcomes with TAVR are at the very least equivalent to surgery, and in some cases better with the TAVR procedure,” said Schultz.
search Re e R co n a i gn ic
Essentia Health Expands TAVR Program
its St. Paul hospital’s pediatric intensive care unit. The health care system has been CLABSI-free for five of the past nine calendar years. In total, the unit has had 2,570 days without a CLABSI, a record for Children’s. Children’s pediatric intensive care unit on its Minneapolis campus is currently running a streak of 500 CLABSI-free days. According to the Centers for Disease Control and Prevention, CLABSIs result in thousands of deaths each year and billions of dollars in added costs. Patsy Stinchfield, senior director of infection prevention and control at Children’s, credits the success of the St. Paul pediatric intensive care unit to a combination of processes implemented at the hospital level and the unit level.
“We know that innovation at the state and community level is essential to improve health outcomes and lower costs. In this model, we will support community-based innovation to deliver local solutions that address a broader array of health-related needs of people across the country,” said Patrick Conway, MD, chief medical officer and deputy administrator for innovation and quality at CMS. The five-year pilot projects will begin May 1.
Research Reco n a gn ici
REQUEST FOR NOMINATIONS This August, Minnesota Physician will publish a feature recognizing physician-directed medical research projects. We invite nominations from our readers. If you or an associate are currently engaged in a medical research project, please contact us, either by phone or through the form below. The research may be from any field and conducted on any level— basic, clinical, community-based, epidemiological, health services-related, etc. The only criterion is that the principal investigator(s) is an MD. Whether the research is conducted in an academic institution, a rural or urban clinic or hospital, a managed-care organization, health system foundation, corporation, or state agency, we welcome its nomination. We will feature as many projects as possible, representing a geographically and institutionally diverse sample. Thank you for your participation. We welcome your assistance in recognizing Minnesota’s outstanding medical research community. To submit online: https://www.surveymonkey.com/r/PhysicianResearch
Name of project: Research site: Funder: Principal investigator(s): Phone and/or email): Comments:
Minnesota Physician Publishing 2812 East 26th Street, Minneapolis, MN 55406
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Please note: All nominations must be received by June 15, 2017 and will be held in confidence. We will contact you and no information will be published without approval from the PI(s).
MINNESOTA PHYSICIAN MAY 2017
specialty pharmacy benefit managers who report anywhere from 90 percent to 94 percent adherence. “Our excellence award recipients have designed proven strategies to address numerous challenges in prescription drug programs,” said Jane Lutz, executive director of the Pharmacy Benefit Management Institute. “We are thrilled to recognize HealthPartners for their great work in the area of Hepatitis C and the positive outcomes they have achieved with their members through this program.”
Sanford Selected for Oncology Clinical Trial Sanford Health is launching a clinical trial to examine whether medications approved by the U.S. Food and Drug Administration (FDA) for one cancer can effectively treat another type of cancer. The health care system’s Bismarck, Fargo, and Sioux Falls locations are participating in the national effort. The study, called the Targeted Agent and Profiling Utilization
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Registry Study (TAPUR), is sponsored by the American Society of Clinical Oncology (ASCO). “Precision cancer therapy shows great promise, but despite our advances in genetic testing, treatment options have been limited,” said Steven Powell, MD, principal investigator for Sanford Health sites. “ASCO’s TAPUR study will increase the treatment options for our patients.” Participants include patients who have had genomic testing done and who are identified to have a targetable alteration. Currently, only adults with advanced cancers that have progressed on standard therapy, or for whom no standard therapy exists, can participate. Those who qualify will gain access to treatments that have been matched to their specific needs. Seven pharmaceutical companies are participating and are giving medications for the study voluntarily—AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly and Co., Genentech, Merck, and Pfizer. More drugs that target additional cancers may be added to the clinical trials as more pharmaceutical companies sign on.
Most Major Heart Attacks Occur in Patients with Normal Cholesterol Results of a Minneapolis Heart Institute study have shown that most patients who have suffered major heart attacks had normal cholesterol levels. In addition, more than half of these patients had not seen a physician in the two years prior to their heart attacks. “The data on statins clearly shows that individuals with normal cholesterol levels can also reduce their risk of heart attacks,” said Michael Miedema, MD, MPH, cardiologist at Minneapolis Heart Institute and principal investigator for the study. Researchers reviewed data, cholesterol values, and prior medical encounters for more than 1,000 patients who were treated for STEMI heart attacks, a serious form of heart attack in which a coronary artery is completely blocked, between Jan. 1, 2011 and Dec. 31, 2014. They also looked at new treatment guidelines for heart disease that were established in 2013. Before the new guidelines, physicians
would typically check a patient’s cholesterol levels and put them on medication if those levels were elevated. “The more recent cholesterol guidelines are clearly a big step in the right direction, but we need to have better systems and incentives in place to get patients the assessment and treatments that could potentially be life-saving,” said Miedema. Researchers found that for this group of heart attack patients, 39 percent would have qualified for a statin medication prior to their heart attack according to the old guidelines whereas 79 percent were statin eligible according to the new guidelines. Now, physicians also look at factors such as age, gender, and high blood pressure. “Heart disease is a multifactorial process, and factors other than cholesterol, like smoking or high blood pressure, can raise your risk even if your cholesterol is normal,” said Miedema. “In fact, we found that the average cholesterol levels in this group of individuals were quite average.” The study was published April 12 in the Journal of the American Heart Association.
John Wagner, MD, professor in the University of Minnesota Medical School’s Department of Pediatrics and executive medical director of the Pediatric Blood & Marrow Transplant Center, has received the 2017 Lifetime Achievement Award from the Pediatric Blood and Marrow Transplant Consortium in recognition of his career supporting research and education, improving the availability, safety, and efficacy of hematopoietic cell transplantation and other cellular therapeutics for children and adolescents. Wagner’s research focuses on the development of new treatments for life-threatening diseases that have unsatisfactory conventional treatments. He is internationally recognized as an expert in the field of stem cells and umbilical cord transplantation and was the first to use umbilical cord blood to treat a child with leukemia in 1990. Wagner serves as the co-director of the Center for Translational Medicine at the University and holds two endowed chairs. He earned his medical degree at Jefferson Medical College, now the Sidney Kimmel Medical College in Philadelphia; completed an internship and residency in pediatrics at Duke University School of Medicine; and completed a postdoctoral fellowship in hematology-oncology at The Johns Hopkins University of Medicine. Claire Bender, MD, has received the inaugural Champion of Allied Health Award from the Mayo Clinic School of Health Sciences Alumni Association for her contributions toward promotion, advocacy, and advancement associated with allied health professions. Bender served as dean of the school from 2002 to 2014. During that time, she led changes that helped professionalize the school and allied health careers, including playing a pivotal role in establishing a University of Minnesota campus in Rochester and developing a Bachelor of Science in Health Professions degree at the university. Bender also led development of blended learning, which combines online and in-person instruction, and interprofessional education. She now serves as a supplemental retired consultant in the Department of Radiology at Mayo Clinic and a professor of radiology. Bender earned her medical degree at the University of Nebraska College of Medicine and completed a radiology residency at Mayo Clinic before joining the staff. Paul Severson, MD, a surgeon from Deerwood, Minn., has received the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Award for Excellence in Humanistic Clinical Care. The award honors individuals who have exhibited excellence in patient care and surgical practice as well as significant surgical-endoscopic skills and contributions to the community. Severson is the co-founder and co-director of the Minnesota Institute for Minimally Invasive Surgery; director of the Minnesota Reflux and Heartburn Center; and program director for Advanced GI MIS/Bariatric and Flexible Endoscopy Fellowship. He is also a member of SAGES Global Affairs committee, which provides tele-education to the residents, faculty, and private practice surgeons in Haiti, and has spent more than 30 years educating surgeons and medical professionals in the U.S. and abroad. In addition, Severson is the founder and CEO of Project Haiti, through which he has made over 70 trips to Haiti to teach laparoscopic and endoscopic surgery. Severson has been a member of the medical staff at Cuyuna Regional Medical Center in Crosby and Riverwood Healthcare Center in Aitkin since 1984. He earned his medical degree at the University of Minnesota and completed his general surgery residency at Hennepin County Medical Center.
Osmo Vänskä /// Music Director
ALSO SPRACH ZARATHUSTRA
INSIDE THE CLASSICS: DVOŘÁK
DAVID ZINMAN RETURNS
STRAUSS’ ALSO SPRACH ZARATHUSTRA Jun 1 | SYMPHONY IN 60 Come early for happy hour, enjoy a shorter performance and stay late for a post-concert onstage gathering with Minnesota Orchestra musicians. Tickets $30 / $20 for patrons under the age of 40
Jun 2-3 | Full Performance Enjoy this program of sweeping orchestral classics including Strauss’ Also sprach Zarathustra made famous by Stanley Kubrick’s 2001: A Space Odyssey.
MOZART AND DEBUSSY Jun 8–11
Juano Menya, Conductor / Ingrid Fliter, piano
Mozart is the ultimate “classical” composer whose every bar of music is perfectly proportioned, balanced and beautiful, while Debussy’s revolution a century later was to build a whole new world of sound.
INSIDE THE CLASSICS
BECOMING LEGEND: DVOŘÁK SYMPHONY NO. 7 Jul 15 Dvořák’s Symphony No. 7 is his most thrilling—the music that put a Prague butcher’s son on the international music map. Tickets $30 / $20 for patrons under the age of 40 Please note: first half is conversation and orchestral excerpts, second half is a full performance
minnesotaorchestra.org 612.371.5656 Ã Orchestra Hall Photo credits available online. All sales final. All artists, dates, programs, prices and times are subject to change.
MINNESOTA PHYSICIAN MAY 2017
The changing face of pharmacy Marilyn K. Speedie, PhD, University of Minnesota College of Pharmacy Reflecting on your career as dean, what have been the biggest changes in the College of Pharmacy curriculum?
In 1995, the College of Pharmacy began its first entry-level Doctor of Pharmacy program. (Previously it had been a five-year bachelor’s level program.) The profession was transitioning to a patient care practice and the education of pharmacists for that practice required a four-year doctoral education with much more focus on pharmacotherapy, medication management, diseases and patients, along with the drugs. We introduced much more experiential education, both in the pharmaceutical care laboratory and in real practice settings.
diseases and conditions. Each individual can get a genetic analysis done for a panel of genes that affect medication use, and your pharmacist should be able to read that analysis and review your medications. How can pharmacists collaborate more with physicians to improve health care?
Pharmacists are the drug experts on the team and can provide the best care of patients with complicated drug regimens. Pharmacists can establish collaborative practice agreements with physicians that allow them to select, monitor, and
All prescription medications undergo rigorous clinical trials to demonstrate safety and efficacy before approval by the FDA. While they may all not be effective in every group of patients due to varying causes of the disease or varying metabolism, all have demonstrated efficacy in an identifiable group of patients. New drugs are being developed constantly and some of those may be more widely efficacious than currently available medications.
The University of Minnesota College of Pharmacy was ranked No. 2 in 2016 by U.S. News & World Report. Please tell us about this.
What can you tell us about pharmacogenomics?
Pharmacogenomics is the science and practice of applying knowledge of a patient’s genetic make-up to the selection of the right drug and the right dose to optimize treatment. People will have a wide variation in the genes that control drug action, drug metabolism, and side effects. Our scientists are studying these phenomena and practitioners are beginning to apply pharmacogenomics in practice. Pharmacogenomics is now pretty standard practice in oncology and for patients using blood thinners, and is expanding in practice to a number of other
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The University of Minnesota Academic Health Center is a leader in interprofessional curricula. We begin the first year with a course that introduces the developing professionals to each other and to the health care system and to teamwork across the professions. It continues into the second year with a course that introduces medical students, pharmacy students, and nursing students to actual patients who are elderly and can teach the students what being a patient is all about. Many commonly prescribed medications are not widely effective. What can you tell us about this issue?
In recent years, we transitioned to a new curriculum that is highly integrated between the basic and clinical sciences, is more interprofessional, involves a big portion of active learning in the classroom, and has a lot more emphasis on public health and community engagement. New topics include pharmacogenomics and informatics.
The U.S. News & World Report rankings are based on reputation among the other 134 pharmacy schools. We enjoy a wonderful reputation due to our leadership and innovation. We produce wonderful pharmacists who are on the cutting edge of practice. National pharmacy organizations are often led by Minnesotans. Our faculty members are well known and excellent and are doing innovative research. We are proud of our ranking and it serves us well in attracting students, faculty, and funders.
The College of Pharmacy is now collaborating with the Medical School to develop coursework for future physicians. Please tell us about this.
Do you feel that any changes are necessary to the FDA’s drug approval process?
“...” role in health Pharmacists’ care is expanding rapidly.
adjust drug therapy for patients. They also can help patients with transitions of care from hospital to other venues and back again, when medications are most susceptible to misuse. While including pharmacists as part of the care team in hospitals has been standard practice for a long time, increasingly physicians in ambulatory care are demanding pharmacists be part of their care teams. They can manage patients with chronic illness, leaving physicians time for more acutely ill patients.
There are certainly tweaks to the process that may be beneficial, but overall I think they do a remarkable job. Pharmacovigilance entails adverse drug reaction reporting. What should physicians know about this?
Physicians should report adverse events to the FDA (there are forms available online) even if they are just suspected to be linked to a specific drug therapy. Clinical trials to prove safety and efficacy can only include a limited number of people and sometimes side effects are uncovered only after a drug is used in a broader population. It is critical that these are reported so that the profile of side effects in the broad population is understood. Medical cannabis has a growing role in health care delivery. What can you tell us about this subject?
Minnesota has one of the most controlled approaches to distributing medical cannabis in
the country. Use under controlled conditions may lead to better information about its efficacy and safety. In Minnesota, physicians are only certifying that patients have a qualifying disease. Pharmacists working for one of the two cannabispreparing companies are involved in the prescribing, preparation, and distribution of the dosage forms. Hopefully there is good follow-up communication with the patients’ physicians so knowledge is developed anecdotally about its efficacy and safety. What does the future hold for the next generation of pharmacists?
The pharmacy profession is an exciting one with an ever-broadening range of health profession employment opportunities. On the practice side, we see more and more pharmacists working in venues where they are the medication experts on a team that provides patient care and works directly alongside nurses, physicians, and others. It is my vision that in rural communities, where there are often no physicians and especially no physician specialists, that the local pharmacy (which most communities have) will serve as the “wellness center.” They will have an exam room (most already have a consultation/exam room) and telemedicine room and be the keeper of patient records and scheduling for telemedicine visits and visits from itinerant health
professionals who come through town periodically and are accessible via telemedicine otherwise. The pharmacist will provide medication management, follow-up for transitions home from a hospital stay, other primary care monitoring of chronic illness, and triage for more acute illness. Many of these tasks are already done in rural communities. This type of arrangement will better coordinate health care for rural citizens and use physicians where they can have the greatest impact.
states such as California and Oregon have passed these actions, with substantial public health impact on their states, and we would like to join them.
The pharmacy professional organizations are working hard to pass “provider status” bills in Congress that would give pharmacists the ability to provide and bill for services covered in our practice act that would fit under Part B of the Medicare law. This will change dramatically the ability of pharmacists to get paid for services to Medicare patients in underserved areas.
Marilyn K. Speedie, PhD, has been dean of
Another area the college is working on is integrating pharmacists into the teams caring for mentally ill patients. We can have a very positive impact on both their mental illness as well as the other chronic illnesses they have concurrently. We are also working in the Legislature to gain authority to prescribe medications that do not require diagnosis such as oral contraceptives, smoking cessation, and travel medications. Other
In summary, pharmacists’ role in health care is expanding rapidly and I am excited to see the results. Pharmacists are already the most accessible health professional. Now we just need to take full advantage of that.
the University of Minnesota College of Pharmacy since 1996 and will be retiring as dean in July 2017. Her leadership interests include developing the college’s education, research, and clinical practice missions, including drug discovery and development and advancing pharmacy practice to improve care for patients. During her tenure as dean she expanded the pharmacy program to the campus of the University of Minnesota, Duluth, established the Center for Leading Healthcare Change, which she also co-directs, and built a national presence for the College of Pharmacy. In 2014 she was awarded the American Pharmacists Association’s highest honor, the Remington Medal Award, for her leadership in the profession.
MINNESOTA PHYSICIAN MAY 2017
3Off-label prescribing from cover The drug approval process
another), when the dose is higher or lower than that which is approved, or when a drug is used to treat a child but it is only indicated for use in adults.
An increase in off-label use
Part of the intensive drug approval process requires drug labeling that OLP is not an unusual practice. According to The Guide to Off-Label is created by the innovator and must be approved by the FDA. The Prescription Drugs by Loughlin et al., an estimated 58 million prescriptions drug labeling provides guidance to providers about the specific diseases/ were used off-label in 1998. By 2003, off-label drug use almost doubled conditions the drug is approved for, how to use to 115 million prescriptions. With the proliferation the drug to treat these diseases/conditions, as in the number of sources about off-label drug well as known risks and adverse events that were information available, OLP continues to increase. identified in clinical trials. When drugs are being Drug reference sources available to prescribers often prescribed for their approved indication, the FDA A study found that contain both labeled and off-label uses. Not only are has determined that the benefits outweigh the risks 78.9 percent of children off-label use information and studies more readily through a careful evaluation of scientific data. discharged from pediatric available to practitioners in today’s society, insurers Once a drug has FDA approval and is marketed, often will cover off-label uses if they are included in hospitals were taking at least health care providers have some latitude to prescribe major compendia. one off-label medication. the drug for unapproved or off-label uses when, in Prazosin their professional judgment, they believe the potential One example of an agent with multiple off-label benefits outweigh the potential risks to their patient. uses is prazosin, an alpha-1 selective antagonist Off-label prescribing (OLP) simply means the that was brought to market under the brand name medication is being prescribed for treatment not specified Minipress. The FDA approved prazosin to treat hypertension, and this in the FDA’s approved packaging label and insert. Off-label drug use includes remains its sole on-label indication. However, off-label use of prazosin has use in indications, formulations, populations and dosing strengths or regimens been garnering increased interest in the treatment of post-traumatic stress that are not FDA approved. Examples of OLP include when the formulation disorder (PTSD). Prazosin is also used off-label to treat poisoning due to is changed (a capsule reformulated into an oral solution), it is being used for Indian red scorpion (Mesobuthus tamulus) venom, as rural areas may lack a different indication (approved for a certain cancer but used off-label for access to particular anti-venom agents and must rely on alternate therapies. Micromedex’s monograph for prazosin lists additional non-FDA approved uses including treatment for benign prostatic hyperplasia, congestive heart failure, diagnosis of erectile dysfunction, and Raynaud’s phenomenon. Fluoxetine SSRIs (selective serotonin reuptake inhibitors) are a class of medications used for a wide variety of off-label drug uses. An example is fluoxetine, which has FDA approval for bulimia nervosa, depressed bipolar I disorder, panic disorder, and major depressive disorder in adult populations. Fluoxetine has also been used for non-FDA-approved conditions with the evidence favoring efficacy in cancer-associated depression and reducing frequency of menopausal hot flashes/sweats. Other wide-ranging off-label uses for SSRIs varying in efficacy, include treatment for Huntington’s disease, obesity, diabetes mellitus-associated depression, prophylaxis for myocardial infarction, and chronic fatigue syndrome.
Becoming common practice OLP has become more common in treating certain conditions such as antipsychotic drug use, orphan diseases, and cancer therapy. Some examples of OLP that have become common practice include, use of aspirin in diabetes for prophylaxis against cardiovascular disease, propranolol for anxiety, and topiramate for weight loss. The rate of OLP is also higher and more common in practice for certain patient groups. A study by Shah et al. (2007) found that 78.9 percent of children discharged from pediatric hospitals were taking at least one off-label medication. Central or autonomic nervous system agents and GI medications were among the most commonly used OLP medications. Keep in mind that many medications are approved without utilizing young children in the clinical trials, so using these agents in this population is by definition OLP even though their use may be theoretically or empirically justified by the prescriber. In a headache specialty practice, Loder and Biondi (2004) reported that off-label use accounted for 47 percent of prescriptions written.
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Seeking FDA approval of off-label use
Regardless of whether a prescription is provided for an approved indication or for an off-label treatment, a provider can be held liable for inappropriate In some cases, the drug proprietor may seek FDA approval for an off-label prescribing in both cases. According to the FDA’s guidance on off-label indication of an already approved medication. The proprietor must file a prescribing, “If physicians use a product for an indication not in the approved supplemental new drug application (sNDA). As described by Wittich and labeling, they have the responsibility to be well informed about the product, Burkle (2012), this application is similar to the original drug application in to base its use on firm scientific rationale and on sound medical evidence, and that extensive data from clinical trials are necessary to demonstrate safety to maintain records of the product’s use and effects. and efficacy for the treatment of the new indication. Use of a marketed product in this manner when the However, proprietors seeking approval for a new intent is the ‘practice of medicine’ does not require indication can skip the preclinical phase and conduct the submission of an Investigational New Drug fewer phase III trials if the new indication is closely Application (IND), Investigational Device Exemption related to an already approved use (Kao, 2016). If (IDE) or review by an Institutional Review Board the FDA approves the supplemental application, the By 2003, off-label drug (IRB).” If the intent is that the drug is being used for proprietor can change the drug labeling to reflect the use almost doubled to research purposes, this would trigger the IND or IDE expanded indication(s). 115 million prescriptions. to be filed. Unfortunately, the definition of research as In instances where off-label drug use becomes it pertains to drug prescribing is not well defined. standard in practice or widely accepted, the drug The FDA does not regulate the practice of manufacturer may not seek FDA approval for the offmedicine and as such, the Federal Food, Drug, label use because approval for an indication can be costly and Cosmetic Act of 1938 should not play a role and time-consuming. According to Serkyaka (2016), in creating physician liability for OLP. Due diligence, running just one phase III trial can cost between $11.5 professional judgment, and acting in the best interest of the patient should million to $52.9 million. Additionally, once approved, the revenue generated be part of any OLP policy. In the May/June 2007 edition of Hematology/ from the new indication may not be enough to offset the cost and time spent Oncology News and Issues, health care law experts James B. Riley, Jr. and seeking approval, especially when the drug is available as a generic or will soon be.
Expanded use It is important to note that while OLP may be widely accepted; there is limited evidence to support off-label use in certain situations. This is more apparent for psychiatric conditions such as depression, schizophrenia, bipolar disorder, and seizures. A recent analysis by Stafford et al. in 2012 specifically looked at drugs that were widely used to treat off-label indications and needed additional study to determine how effective and safe they are for their off-label uses. The study identified 14 drugs that meet these criteria, nine of which were used off label for psychiatric conditions.
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As new agents continue to be FDA approved within these specialty areas such as many of the new biologic drugs, distribution of off-label drug information continues to expand. This allows for early adoption of novel treatments by physicians and prescribers because the FDA approval process is long, complex, and costly. In this aspect, off-label drug use benefits medical science and allows for increased drug discovery. For example with orphan diseases, off-label drug use has increasingly been used with more novel drug products being introduced into the market. Rare diseases often rely on OLP because there is little incentive for manufacturers to conduct extensive, expensive clinical trials for an indication approval that benefits the few.
Liability While OLP is allowed via the providers’ professional judgment and responsibility, marketing off-label use by the proprietor or their agent is not! Pharmaceutical manufacturers, like any other business, are charged to provide value for their investors. This is an obvious conflict of interest when you consider what may be best for the patient. Pfizer was the poster child for off-label conflicts of interest. They have settled several cases over illegal marketing practices since 2002. In 2009, the government charged that Pfizer executives and sales reps planned and executed schemes to illegally market Bextra, Geodon, Zyvox, and Lyrica. Pfizer chose to settle the civil and criminal charges for $2.3 billion. This settlement was the largest in history, yet amounted to less than three weeks of sales for Pfizer at the time. MINNESOTA PHYSICIAN MAY 2017
3Quality improvement from cover
• Plan: Defining objectives and articulating the plan (who, when, where). • Do: Carrying out the plan while collecting data to track progress. • Check: Comparing observed to expected results through data.
Dr. Jones begins Tim’s evaluation by reviewing his previous chart and the notes entered in the EHR by her medical assistant. She continues her evaluation by collecting Tim’s medical history, performing a physical examination, and ordering lab tests. Finally, she reviews her assessment with Tim and his wife. Together they co-create a plan of care for his elevated BP, which includes lifestyle modification and starting a new medication.
• Act/Adjust: If successful, this process becomes the new standard, if not, the plan is adjusted and a new PDCA cycle is begun. QI models like PDCA are being increasingly used in health care to improve systems and processes of care in order to improve health outcomes. Metrics that are tracked can be broadly divided into those that measure how the system is working (process metrics) and those that measure the impact or results (outcomes metrics). For example, for coronary intervention, time from door to balloon is a process metric, while mortality rate is an outcome metric.
How we think as physicians already includes the Plan-Do-Check-Adjust method.
Let’s use a very simple case study of a patient seeing a physician for hypertension in order to study how PDCA actually works. A 66-year-old male patient named Tim, who is accompanied by his wife Jane, arrives for his first visit with Dr. Jones in order to discuss his blood pressure (BP) that was found to be 186/100 recently at a free retail clinic. Tim is overweight, has high cholesterol, and also has a long history of smoking.
Step 1. Choosing the problem: Before beginning a PDCA cycle it is critical that the organization clearly identify the problems that need tackling and then prioritize which problem to focus on. It is important to analyze and choose the problems by looking at concrete data as well as getting broad input from internal and external stakeholders including patients. Based on Tim’s medical history and physical exam, Dr. Jones confirms the diagnosis of elevated BP so they focus their efforts on his hypertension.
Step 2. Determining what the baseline is: Part of the QI scientific method involves astute observation and documentation of the current baseline. This step is critical because it allows the organization to specify metrics of success as well as track the effects of the PDCA cycle as compared to the baseline. Organizations use both process and outcome metrics to monitor progress and set targets. Dr. Jones carefully pieces together data from Tim’s history, examination, labs, and previous records to diagnose Tim’s hypertension. It is against this baseline that she will track Tim’s progress over time. Step 3. Forming the team: Next, organizations begin the important task of putting together the right team to perform the PDCA cycle. Typically, stakeholders that are directly involved in the work are chosen. It is critical that front-line staff be involved from the outset because they hold critical information concerning which issues need to be solved and what barriers may be encountered. For a clinic-based QI project, for example, physicians, medical assistants, receptionists, coders, and the clinic manager may comprise the improvement team. Organizations that forget to involve front-line caregivers are destined to fail. Increasingly, there is a movement to also involve patients in QI and assemble a formal Patient and Family Advisory Council (PFAC) in order to include the patient/family voice. It’s also a good idea to carefully evaluate and adjust the current workload of team members so that the new QI project is adequately resourced. Dr. Jones astutely involves both Tim and his wife in the plan of care having discovered that Jane is an avid cook. Step 4: Articulating the plan: For any PDCA cycle to be successful, metrics, goals, timelines, and accountabilities need to be carefully understood and clearly communicated. It is helpful to think through the steps in the plan and consider both the intended and unintended consequences to patients, staff, and other organizational processes. Keeping all involved stakeholders in the loop is key so that everyone remains on the same page and surprises and barriers can be minimized. Finally, all aspects of the plan, including goals, metrics of success, timelines, etc., are recorded on a document that is accessible to all team members. Many organizations use a “visual control method” by posting all these documents on a wall where the QI team can huddle to communicate and track progress.
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Dr. Jones provides the new prescription; prints out information; asks Tim and his wife lots of questions in order to gauge their comprehension and assess their social determinants of health. She also sets a target BP level and timeline for the next appointment; and, documents this plan in the chart that Tim can access from home. Clear recommendations regarding side effects to watch for, when to reach out to the clinic, and when to return for a follow-up visit are given to Tim and recorded in the EHR.
Do Tim and his wife return home and diligently begin following the care plan noted in Timâ€™s electronic chart. The clinic staff performs their part of the plan by monitoring and logging any calls or e-messages from their new patient. Step 1: Executing the plan: Organizations are now ready to execute the plan. Those who have spent adequate time and resources in the Plan phase frequently find the Do phase to be easier as a result.
is necessary. This data-driven approach demands that both qualitative and quantitative data is collected and analyzed in real-time on a graph that depicts the baseline as well as the upper and lower control limits. Ongoing communication among all the stakeholders in this phase is critical. Organizations use various tactics such as scheduled and ad hoc team huddles to review progress and discuss any barriers. Tim checks his BP at home every other day and carefully records the numbers in his chart. He and his wife also use a mobile phone app to track his diet, exercise, and weight.
QI models like PDCA are being increasingly used in health care to improve systems and processes.
Tim and Jane proceed with the care plan by making dietary changes, exercising, and promptly filling the new prescription after consulting with their local community pharmacist. Step 2: Monitoring performance: Organizations carefully monitor all the incoming data as the plan proceeds with a watchful eye toward both intended and unintended consequences. Data and trends are evaluated and reported in order to track progress and watch for signs that intervention
Step 3: Creating frequent touch points: Besides trending data, it is important to monitor how the PDCA cycle affects staff morale, physician relationships, and others involved in the process. For any QI project to succeed, leaders must be engaged, staff must be integrally involved, and trust among all is key.
The clinic has automated much of the follow-up process with Tim by sending weekly e-reminders to help him adhere to his medication regimen and to inquire about side effects or questions that he may have.
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3Quality improvement from page 19 Check Tim and his wife arrive for his one-month follow-up visit and review their home BP trends with Dr. Jones. Dr. Jones checks whether any urgent visits or calls were received in the interim and performs a one-month check up. Step 1: Checking outcome metrics: Data is collected after the Do phase is over and compared to the expected result from the initial PDCA Plan in order to gauge whether quality improvement was attained. Data trends throughout the life of the project are also reviewed to reveal important lessons learned. Dr. Jones reviews the home BP readings and the BP taken during Timâ€™s office visit. Step 2: Checking process metrics: Itâ€™s important to assess the process itself by determining whether each step in the plan was completed, how much time it took to complete each step, how well the team completed its work, and the effect on patients and staff. During the follow-up visit, Dr. Jones asks Tim if he took his medication regularly, how it worked for the family to reduce salt in their diet, and whether Tim or his wife noted any other effects. They both report that Tim seems to have more energy and the daily walks they have been taking have led to reduced screen time and provided time to rekindle their marriage. Step 3: Reflecting on the PDCA cycle itself: A critical and often forgotten step in any QI project is to analyze how the PDCA cycle itself
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worked. The project team and other important stakeholders are asked structured questions about their perception of the project, the wins, and any barriers in order to improve the process going forward. Well-performed reflections from a QI project cannot only improve the quality of future project plans but also the overall QI process within the organization. Dr. Jones asks what Tim and Jane have taken away from their first month in treating a chronic condition like hypertension. Impressed that Tim sought the advice of his trusted community pharmacist before starting the prescription, Dr. Jones decides to build this step into future care plans for other patients. Step 4: Finalizing the result: Based on the criteria articulated in the Plan, the PDCA cycle can be deemed successful if the results exceed the expectations. Organizations should continuously strive for quality improvement by relying on various inputs such as quality data, patient surveys, and staff recommendations. Dr. Jones informs Tim and his wife that although his BP has decreased to 170/92, it remains higher than the acceptable range given his other co-morbidities. Their team has more work to do.
Adjust Given that the BP remains high, Dr. Jones recommends that Timâ€™s medication be increased and encourages him to continue with lifestyle modifications. Step 1: Adjusting the plan: Based on the various inputs including process and outcome metrics, lessons learned through structured reflection, and leadership, staff and patient feedback, the plan is adjusted to continue the QI process. It is critical that any QI Plan not be adjusted without properly cycling through the Do and Check phases so as not to miss important lessons.
Dr. Jones discusses the pros and cons of three different approaches: 1) wait and watch while continuing the same dose of medication; 2) increase the dose of the current medication; or, 3) switch to a different medication. She asks openended questions to engage Tim and Jane as they adjust his care plan.
project succeeds, but it may be just as important when the goals are not met. Expanding to a new PDCA model that incorporates celebration into the QI process, will ensure that the hard work of staff is recognized and may help reduce health care staff burnout.
Dr. Jones and her medical assistant have fallen into a habit of doing a loud Step 2: Preparing to launch the next PDCA cycle: The new plan high five and a standing cheer for patients who follow through on their plan of care. replaces the previous plan as the new standard and all the other steps noted Tim and his wife are surprised, heartened, and reinvigorated when at their threein the Plan section need to be repeatedâ€”including month visit they are cheered in this fashion for success in clearly articulating the new current state through controlling Timâ€™s blood pressure! observation, redefining the problem by incorporating the last PDCA lessons, re-evaluating the project team QI paradigms like PDCA cycles may sound composition, communicating broadly what the next burdensome and complex on the surface but when steps are, and putting together the new plan with you take the time to look under the hood, they can Organizations should expected outcomes in a shared team space. be simple, intuitive, and even a lot of fun. After all, continuously strive for quality how we think as physicians already includes the PlanTim and Jane discuss the options Dr. Jones presented improvement. Do-Check-Adjust method and thus using the PDCA and decide to have her increase the dose of his current model to achieve quality improvement is not much BP medication. They also recommit to continued of a stretch. Fully engaging in quality improvement lifestyle modifications. activities will allow us to serve our patients and Celebrate communities even better by improving the overall Most people who work in health care want to allay human health care system! suffering. In this time of increased burdens on staff such as duplicative quality measurement, regulatory overload, and cumbersome electronic Rahul Koranne, MD, MBA, FACP, is an internist and geriatrician who is systems, it is critical that we incorporate gratitude and appreciation into any passionate about making Minnesota the best state to receive and provide health improvement process. Building a structured recognition and celebration care by focusing on the quadruple aim and social determinants of health. He process into any QI project can help reduce stress levels, pull teams together, serves as the chief medical officer of the Minnesota Hospital Association. and enhance performance. It is critical to not just celebrate when a QI
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PROFESSIONAL UPDATE: WOMEN’S HEALTH
Treating older female patients Common medical issues BY AMY DIEDE, MD
s a family medicine physician, I treat patients of all ages and have learned that it takes more diligence to identify, diagnose, and treat some of the more common medical conditions in older women. The average 75-year-old has at least three chronic conditions and takes five or more medications, according to “About Medical Care for the Elderly” by Thomas Day, director of the National Care Planning Council. In addition, some older patients may be reluctant to admit to physical problems or limitations for fear of treatment or changes in lifestyle. Following are some lessons I’ve learned through the years when treating older women patients.
Screenings and immunizations Standard protocol suggests yearly mammograms for women, beginning at the age of 40, unless a woman is at high risk for breast cancer or has an immediate issue. Changes in breast density as women age make it more difficult to detect problems with a physical exam, making mammograms even more important.
Most physicians today follow guidelines recommending Pap testing every three years until the age of 65, if previous tests for cervical cancer have been negative. After that, barring any new issues, they can be discontinued. DEXA scans are important for women with osteopenia or osteoporosis to evaluate any change in severity. According to the American Congress of Obstetricians and Gynecologists, osteoporosis is five times more prevalent in women than in men. It recommends DEXA screening beginning at age 65 or sooner if a woman is at higher risk. Colonoscopies are suggested for all patients, beginning at the age of 50, and then every 10 years if the results are normal. Women (and men) at high risk for colon cancer, or those with polyps or abnormal colonoscopy results, should repeat the test every three to five years. Immunizations are important, as well. Everyone should have a tetanus vaccine every 10 years and a flu shot every year. The shingles (Zoster) vaccine only needs to be given once but is important in preventing or reducing the severity of shingles. To prevent or reduce the complications of pneumonia, your patients should receive both the Pneumovax 23 and Prevnar 13 pneumonia vaccines. They are recommended for all adults over 65.
Menopause symptoms Some older women may need help navigating the side effects of menopause, from hot flashes and mood changes to weight gain and vaginal dryness. While there are numerous hormone therapies on the market today, most physicians prefer to limit the length of time they prescribe these medications, due to the long-term side effects, which can include cancer. In 2013, the U.S. Food and Drug Administration approved Brisdelle (paroxetine) as the first nonhormonal treatment for moderate to severe vasomotor symptoms, including hot flashes. Other non-hormonal options also exist to help with menopausal symptoms, and a variety of lubricants are available for vaginal dryness.
Risk for heart disease One in four women will die from heart disease, according to the National Heart, Lung and Blood Institute, and the risk increases with a woman’s age. We need to be vigilant about evaluating for symptoms that patients might not connect with high blood pressure, a risk factor for stroke and heart disease. Ask them about frequent headaches, dizziness, and ringing in the ears. Coronary artery disease is the most common cause of heart disease. Make sure your patients know the warning signs of heart disease, including fatigue, shortness of breath, nausea or indigestion, jaw or throat pain, or pain in the left arm.
Urinary incontinence Many older women suffer in silence from urinary incontinence (stress incontinence, urge incontinence, or overactive bladder) because of their reluctance to bring up such a private issue with their physician. Yet, today there are drugs, surgical treatments, and implanted devices, such as the InterStim Therapy System, that are highly effective for urinary incontinence. Sometimes urinary incontinence is caused by vaginal atrophy or pelvic prolapse. According to Vanessa Knoedler, MD, gynecologist with Metro OBGYN, pelvic organ prolapse affects as many as 35 percent of adult women worldwide and is associated with age and obesity. In addition to
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lifestyle changes, physical therapy, and Kegel exercises, women with pelvic prolapse can be treated with pessaries and surgery.
Discussions about medications Many older women take multiple medications daily, increasing their risks for side effects, negative interactions, and addiction, especially to narcotic pain medications. Make sure to update a patient’s medication list diligently at each visit. In addition, test for liver and kidney function, as impairment in either can alter the effectiveness of a medication. Non-compliance can also be a factor in elderly patients, especially those with limited incomes who may have to choose between purchasing a medicine and buying groceries.
Impaired hearing and vision According to experts at Hearing Health, more than 80 percent of individuals with clinically advanced hearing loss are never diagnosed or treated. A routine hearing screening by licensed clinical staff taking only 30 to 45 seconds is now part of every complete Apple Valley Medical Clinic exam for adults 55 and older. If follow up is needed, we offer comprehensive four-part audiometry, video otoscopy, or referral for ENT consultation and testing. Vision problems, too, are common in elderly women. Macular degeneration, glaucoma, and cataracts are the most common diagnoses. Watch for signs that your patient may not see as well as she should, and refer her to an ophthalmologist if you suspect a vision deficiency.
as patients age there is a tendency to become more sedentary, making it more important for us to stress the benefits of physical activity. Even seemingly minor exercises can result in less joint pain from osteoarthritis, lower blood pressure, less depression, fewer heart attacks, lower incidence of cancer and diabetes, fewer life-threatening falls, and the possibility of reducing the number of medications. As a family medicine physician, I am honored to care for patients of all ages and look forward to helping my female patients enter their later years with grace, happiness, and good health. Amy Diede, MD, is a board-certified family medicine physician with the Apple Valley Medical Clinic.
Dementia and Alzheimer’s disease Older women patients may become forgetful and somewhat confused at times, but dementia is not a normal part of aging. Alzheimer’s disease is a specific form of dementia and accounts for up to 80 percent of all cases, according to the Alzheimer’s Association. Certain signs to watch for include changes in a patient’s mood or personality, withdrawal from activities she used to enjoy, change in judgment, difficulty speaking or writing, and confusion about time and place. Spend a little time probing for signs of dementia with the use of simple mental status evaluations.
Some older patients may be reluctant to admit to physical problems or limitations.
Screening for depression Taking time in a primary care visit to screen for depression can be difficult, but depression is a common comorbidity of certain illnesses that affect elderly women, such as arthritis, diabetes, thyroid disorders, and heart disease. Older adults are often misdiagnosed and undertreated, according to the Centers for Disease Control and Prevention’s “Mental Health and Aging” website. This is because health care providers may see symptoms of depression as a reaction to illness or life changes, and the patient may not seek help because she doesn’t know she could feel better with treatment. Anti-depression drugs and psychotherapy can be effective treatments for depression, even in elderly patients.
Exercise and proper nutrition As our patients age and their metabolism changes, they often face a higher propensity toward obesity. Remind them that being overweight can lead to joint degeneration, heart problems, stroke, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and other conditions. In addition, MINNESOTA PHYSICIAN MAY 2017
Guidelines for care transitions Addressing patients with limited resources BY ANN FIALA, RN, BSN, CPHRM, CHC
he Centers for Medicare & Medicaid Services (CMS) has defined care transition as, “The movement of a patient from one setting of care (hospital, ambulatory primary care practice, ambulatory specialty care practice, long-term care, home health, rehabilitation facility) to another.” The best indicator of care transition success centers on hospital readmission rates. As reported by the Agency for Healthcare Research and Quality (AHRQ), past readmission initiatives have focused on the Medicare population, even though data suggest adult non-obstetric Medicaid patients are more likely to be readmitted for chronic disease exacerbation than Medicare patients. As reported in the Pittsburgh Post-Gazette and Milwaukee Journal Sentinel, studies have shown that socioeconomic status has a direct correlation to overall health and well-being. The Accountable Care Act (ACA) has provided insurance coverage to many individuals who previously would not be afforded such coverage, but gaps persist. And while millions of Americans now have some form of health coverage, the fundamental problems of poverty remain. According to an article titled, “White Paper
of Income and Health” from the Minnesota Department of Health, limited access to community services, primary care, nutritious foods, safe neighborhoods, quality education, and housing remain socioeconomic barriers to wellness. Those same issues contribute to high readmission rates.
The ASPIRE guide Recognizing that the Medicaid readmission issue had not been addressed through previous initiatives, AHRQ developed ASPIRE. The ASPIRE model focuses on the Medicaid population and addresses the “whole person needs” (clinical, behavioral, and social) of the individual. The principles can apply to all payer classifications and the guide helps organizations identify their unique structure and community base, thus facilitating the development of site specific interventions. The ASPIRE guide focuses on six steps. 1. Analyze your data. The first step in any process improvement project is understanding the problem. Analyzing your organization’s specific readmission patterns and identifying those patients at highest risk will provide key information needed to establish actionable goals. Be sure to include data obtained from patient and family member interviews regarding the human factors that led to readmission (e.g., inability to pay for medication, no primary care provider, and homelessness). 2. Survey your current readmission reduction efforts. Inventory the readmission initiatives within and outside of your organization. Once your survey is complete, conduct a gap analysis to evaluate if your efforts are meeting the needs of your targeted populations. 3. Plan a multifaceted, data-informed portfolio of strategies. Based on the qualitative and quantitative data and gap analysis results, develop a goal/aim statement. Build a plan to address your highest risk areas through internal, community, and enhanced services. Ongoing measurement is crucial to ensuring success or the need to change direction if your plan is not having the desired impact. 4. Implement whole-person transitional care for all. Evaluating a patient’s clinical, behavioral, and social needs will provide insight into their personal preferences and living situation. Evaluating whether a patient’s basic non-clinical needs are being met may proactively identify significant barriers to a successful discharge. By honoring “where patients are at” in their lives and communicating simply, the health care team (including the patient and family members) can develop care plans that provide the kind of support they want and enhance overall compliance. 5. Reach out and collaborate with cross-continuum providers. Know the resources in your community. Often these services go unused because health care providers are unaware of their existence. Minnesota offers a variety of social- and health-related programs, many of which are listed at http://mn.bridgetobenefits.org/Home2. Work with your team to develop a community resource guide of relevant services in your area. 6. Enhance services to high-risk patients. Enhanced services go beyond standard care to meet the needs of high utilizers. These services often
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involve additional resources, so they should be data-driven and focused. Many organizations have specialized care navigators or interdisciplinary care transition teams to assist discharged patients with all aspects of their care. These services are not provided to all patients, only those at highest risk for readmission.
order to keep patients healthy, social services teams and a behavioral health integration approach were developed to address non-medical issues. The social workers would assist patients with issues such as housing, appropriate footwear, utilities, sober houses, and food. They have realized an annual cost reduction of 11 percent since 2012.
Patient-centered medical home Thanks, in part, to the ACA, primary care clinics are also reevaluating traditional care How to help? models. The patient-centered medical home Navigating the complex systems of health The best indicator of care (PCMH) shows promise in offering higher quality, care transition is challenging in the best of transition success centers on increased access, and decreased costs. The PCMH circumstances, but becomes even more so hospital readmission rates. payment structure focuses on quality outcomes as when addressing the ongoing needs of patients opposed to service volumes. By utilizing a team with limited resources. Several organizations approach, involving physicians, social workers, throughout the country have found success by nurses, nutritionists, and pharmacists, the PCMH getting creative and implementing innovative addresses whole person care management issues. approaches to care management. According to the National Conference of State Safety-net accountable care organization Legislatures, “Integration of all aspects of health care offer potential to Hennepin County Medical Center (HCMC) in Minneapolis was featured improve physical health, behavioral health, access to community-based in The New York Times for successfully implementing a pilot program social services and management of chronic conditions.” (Safety-Net Accountable Care Organization [ACO] Demonstration) Many Minnesota clinics implemented PCMH well in advance of ACA aimed at reducing avoidable hospital use. The hospital agreed to be paid incentives. According to a study released by the University of Minnesota a fixed amount per patient. If it succeeded in keeping patients out of the and reported in the StarTribune, “Clinics that take more responsibility for hospital, it was allowed to keep whatever money was left over. By forgoing the traditional fee-for-service payment model, the organization could use Guidelines for care transitions to page 404 its dollars in new ways. Recognizing that basic needs must be addressed in The ASPIRE guide is available at no cost on the AHRQ website at http://bit.ly/2nW8zkg
MINNESOTA PHYSICIAN MAY 2017
Open fetal surgery Early treatment for spina bifida BY BRAD FELTIS, MD, PHD
The MOMS study Prior to 2003, open fetal surgery (OFS) was performed experimentally in an effort to reduce long-term comorbidities of spina bifida. Outcomes of these prenatal surgeries were compared with historical postnatal controls and did not examine the safety aspects of the surgery.
n average, there are approximately 1,500 babies born in the U.S. with myelomeningocele, a serious form of spina bifida. Spina bifida is a congenital defect that occurs when the infant’s spinal column doesn’t form and close completely, leaving the There are approximately spinal cord and nerves exposed at any level along 1,500 babies born in the U.S. the spine. This condition can cause traumatic with myelomeningocele, injury to the spinal cord, resulting in physical and a serious form of spina bifida. intellectual disabilities that range in severity. At the Midwest Fetal Care Center (MWFCC), a collaboration between Children’s Minnesota and Allina Health, families have access to a full range of complex and advanced services that provide optimal care for children with a diagnosis of spina bifida. These services start with prenatal diagnosis and include prenatal as well as postnatal options for intervention and treatment.
In 2003, a National Institutes of Health sponsored study was initiated to determine whether performing OFS in utero could minimize neurologic damage and improve outcomes compared to standard postnatal repair. This was known as the Management of Myelomeningocele Study (MOMS). The randomized, controlled trial featured 183 myelomeningocele patients and studied the effects of surgery between 19 to 26 weeks of gestation. Ultimately, the research showed that babies undergoing fetal surgery fared much better than babies undergoing standard postnatal repair. Specifically, the study documented a dramatic reduction in the rate of shunt placement to treat hydrocephalus, as well as improvements in neurocognitive function and independent ambulation. The study also showed that prenatal surgery generally results in the reversal of the hindbrain herniation, known as Chiari II malformation.
Identifying candidates Spina bifida is generally diagnosed in one of two ways. An elevated maternal serum alpha-fetoprotein can tip off a primary caregiver that the baby may have a neural tube defect. Alternatively, a routine 20 week ultrasound can identify spina bifida defects. Once diagnosed, the mother is referred to a tertiary fetal care center such as the MWFCC, where she will go through additional testing to confirm the diagnosis and work with doctors to determine a long-term care plan. In addition to the strict inclusion and exclusion criteria for OFS outlined in the MOMS Study, the following factors are thoroughly vetted when considering whether or not a family is a candidate: • Is the family able to comply with the post-operative care plan? • What are the comorbidities of the mother and infant? • What is the potential of the surgery to positively affect the infant’s disease process? • What is the presence of a support network, both for the baby and the parent(s)? • Did the ultrasound indicate characteristics that are favorable for prenatal repair? After this comprehensive evaluation, a care team of pediatric surgeons, pediatric neurosurgeons, pediatric cardiologists, neonatologists, social workers, nurse specialists, a maternal fetal specialist, and a clinical ethicist meet to discuss each patient and determine both their eligibility and their
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suitability for this procedure. If the family meets all of the strict criteria for OFS, they are thoroughly counseled about the risks and benefits of the procedure versus standard postnatal repair.
The procedure The mother is admitted to the center the night before the surgery will be performed. In the operating room, there are 20–25 clinicians on hand. In addition to the previously mentioned specialists, the full OFS team also includes adult and pediatric anesthesiologists and operative nursing and technical support staff.
complex babies. Before this program was offered, a patient’s only option was to travel to a different part of the country to access similar care, adding unnecessary stress and complication to an already overwhelming situation. Looking ahead to the future of fetal surgery and what patients and expectant mothers can hope for, Children’s Minnesota aims to provide the highest quality, most trusted care available. Teams are staffed with the most qualified medical practitioners, ethicists, social workers, and nurses to guarantee our patients will be cared for by some of the best in the world. Also, by working closely with these individuals, Children’s is able to continue to improve the quality of care and bring advancements to the program each year.
The surgery begins with the mother receiving general anesthesia, which also helps to relax the uterus and to anesthetize the fetus. The abdomen is entered via transverse incision. The uterus is exposed and using ultrasound, the baby is ideally positioned within Research showed that the uterus. A maternal-fetal medicine specialist babies undergoing fetal uses a sterile intraoperative ultrasound to map the surgery fared much better position of the placenta and the baby is rotated so than babies undergoing that the back is up and the neural tube defect is standard postnatal repair. visible. Next, a small hysterotomy is created with cautery and is expanded using a special stapling device that delivers dissolvable staples that pinch off the blood vessels and keep the membranes medicine and surgery at secured to the muscle. Once the defect is exposed, a pediatric neurosurgeon removes the myelomeningocele (MMC) sac—if one is present—and then returns the neural elements to the spinal canal. The surrounding tissue and skin are mobilized over the defect and sewn together in such a fashion as to create a watertight barrier that protects the spinal cord from exposure to the amniotic fluid. The uterus and the abdominal incision are then closed to complete the procedure. The entire surgery takes approximately two hours.
Brad Feltis, MD, PhD, is surgical director of the Midwest Fetal Care Center at Children’s Minnesota. He is one of the world’s few pediatric surgeons who specializes in diagnosing and treating anomalies in developing babies while they are still in the womb and he completed his pediatric surgery fellowship at the University of Washington Seattle Children’s Medical Center. He furthered his training in fetal two of the world’s most acclaimed centers in San
Francisco and Leuven, Belgium. He is active in the North American Fetal Therapy Network (NAFTET).
Post-op The mother typically remains in the hospital for four to five days before she is able to return home. She has weekly ultrasounds to monitor the baby and the uterus and is allowed light activity until delivery. Ideally, the infant will reach 36 weeks gestation before being delivered via caesarean section. All babies who undergo OFS will spend time in the neonatal intensive care unit (NICU) but their length of stay will depend on when they were born. In the days following birth, the baby is assessed by a variety of specialists such as a neonatologist, orthopedic surgeon, pediatric surgeon, neurosurgeon, and urologist. Typically, infants who reach 36 weeks gestation go home after one week, while babies born earlier may need to stay longer. At Children’s Minnesota, a comprehensive program for patients with spina bifida allows the team to remain in close contact with the patient and family for their entire life. Keeping the original care team consistent throughout the patient’s journey is a priority, as the extensive knowledge the team gained during the surgery and after is of extreme benefit to their ongoing care.
Looking ahead Earlier last year, the Midwest Fetal Care Center joined fewer than a dozen other hospitals in North America that offer open fetal surgery, providing families in the region with access to programs able to care for the most
MINNESOTA PHYSICIAN MAY 2017
Gender dysphoria in children and adolescents What physicians need to know BY JAMIE FELDMAN, MD
ndividuals of all ages with gender behaviors, expression, and identities that differ from the cultural norms associated with their assigned sex at birth have been described as “gender nonconforming,” or most commonly, “transgender.” Many, but not all, gender nonconforming or transgender individuals experience gender dysphoria, discomfort caused by the discrepancy between a person’s experienced gender and their sex assigned at birth. According to Dr. Johanna Olson-Kennedy and other international researchers in the April 2016 issue of Current Opinion in Endocrinology, Diabetes and Obesity, an increasing number of preadolescents and adolescents throughout Europe, Australia, and North America are identifying as gender non-conforming or transgender, and are seeking medical services to reduce dysphoria. These interventions include the suppression of physical puberty, and the use of gender affirming (cross sex hormones) to develop physical characteristics consistent with their experienced gender.
Gender nonconforming children and early adolescents According to the World Professional Association for Transgender Health (WPATH), children as young as two may express gender nonconformity. Most do not continue to have gender dysphoria or gender nonconformity as adolescents or adults, and research is ongoing to identify predictors of persistence. WPATH, the Endocrine Society, and other professional organizations do not recommend medical interventions for children. Interventions at this stage focus on gender exploration, as well as social, psychological, and family supports. According to Dr. Annelou L.C. de Vries and colleagues in a 2016 review in the Pediactric Clinics of North America, the ages 10 to 13 years appeared critical for gender identity development in adolescents. The experience of physical puberty, the first romantic feelings, and changes in gendered social relationships at that time are considered important factors. Gender dysphoria that continues through the onset of puberty or increases at puberty is unlikely to desist. Adolescence is often a time of marked distress for trans youth given the pubertal development of secondary sex characteristics that may differ from the internal sense of gender. As a result, adolescents may begin to seek therapy and consider pubertal suppression or hormone therapy. Trans adolescents are at increased risk of depression, anxiety, and attempted suicide as demonstrated in multiple studies. According to the American Psychological Association, issues of self-harm, suicidality, PTSD, substance abuse, and body image among trans youth are often related to external factors such as peer bullying, family/parental rejection, trauma, lack of financial support, co-occurring psychiatric problems, and anatomic dysphoria, rather than gender diversity in and of itself. Supportive psychotherapy, appropriate mental health interventions and medical gender affirmation, including hormonal interventions, have been associated with a reduction in behavioral and emotional symptoms.
Puberty suppression Hormonal interventions to delay or suppress puberty in gender dysphoric youth have been in use since the late-1990s, with the earliest literature primarily from the Netherlands. The goals of puberty suppression are 1) to allow trans youth time to explore their gender nonconformity and other developmental issues without the physical and emotional changes of ongoing puberty, and 2) to potentially facilitate later transition by preventing the development of sex characteristics that are difficult or impossible to reverse with use of gender confirming hormones or procedures. WPATH and the Endocrine Society advocate that puberty suppression occur in the context of a multidisciplinary team involving mental health professionals experienced in gender, pediatric/adolescent medical specialists (both primary care and gender specialists), and potentially surgeons, if gender confirmation surgeries are being considered. Unfortunately, such teams are uncommon
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in most regions, but individual gender specialists in field can form a “virtual team” with excellent communication. Both individual specialists and multidisciplinary teams are available in the Twin Cities and now Rochester, Minnesota. Adolescents should experience pubertal changes to Tanner 2 prior to starting suppression; after that point, the exact timing for initiating suppression will vary with patients and families. Many trans youth present for care later in puberty and suppression can still be helpful both physically and emotionally. The WPATH Criteria for starting puberty suppression are found in the sidebar below.
of body and facial hair will regress or halt. Height growth may slow, with a possible concurrent increase in body fat percentage and decrease in lean muscle mass. Current evidence does not show an overall change in body mass index or other metabolic parameters such as lipids or glucose. These effects are fully reversible, and puberty resumes once GnRH analogues are stopped. Puberty suppression is continued until youth are well established in their gender identity, and cognitively and emotionally mature enough to make decisions regarding gender-affirming Gender dysphoria that hormones, usually around age 16. The risks and continues through the onset of benefits of delaying hormone therapy until 16 puberty or increases at puberty may include effects on bone health and increasing is unlikely to desist. physical differences from age matched peers, with potentially negative consequences for emotional well-being.
Puberty suppression is usually achieved with the use of GnRh analogues, leuprolide being the most common in the U.S. If begun in early puberty, the slight development of secondary sex characteristics will regress, and if begun later in puberty, further development will be halted. Menses will stop, breast development will halt and breasts may become atrophic. Testicular volume decreases, development
RITERIA FOR PUBERTY C SUPPRESSING HORMONES
Effect on bone density and brain development Two common concerns are impacts on bone density and brain development. Multiple studies suggest that loss of bone density may occur during the use of GnRH analogues, however this loss appears to be regained with subsequent estrogen or testosterone therapy. It is important to ensure adequate intake of calcium and vitamin D, routine monitoring of 25-hydroxyvitamin D levels, and encourage weight-bearing activity. No long-term data exists on lifetime risk for osteoporosis in these patients. Significant cognitive development and brain maturation occurs Gender dysphoria in children and adolescents to page 304
Per the WPATH Standards of Care 7 (2012)
In order for adolescents to receive puberty suppressing hormones, the following minimum criteria must be met:
14 The adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed);
24 G ender dysphoria emerged or worsened with the onset of puberty;
34 A ny co-existing psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment;
44 The adolescent has given informed consent and, particularly when the adolescent has not reached the age of medical consent, the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process. Printed with permission from the World Professional Association for Transgender Health (WPATH) and Coleman, Bockting, and Botzer, et al., “Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7.” International Journal of Transgenderism 13(4) (2012): 165–232. Please note: The WPATH Standards of Care are subject to revision when new medical evidence supports relevant changes. To ensure you are referring to the latest edition of this information, please check for updates in the Publications section at www.wpath.org.
MINNESOTA PHYSICIAN MAY 2017
3Gender dysphoria in children and adolescents from page 29
Fertility Future fertility does not appear to be impacted if GnRH analogues are ultimately discontinued, with the resumption of original puberty. However, during puberty, and according to a 2016 review in Pediatric Clinics of trans youth who proceed directly to gender affirming hormone therapy, North America by Drs. Annelou L.C. de Vries, Daniel Klink, and Peggy especially those who begin puberty suppression prior to development T. Cohen-Kettenis, early studies demonstrate that puberty suppression of sufficiently mature ovaries or testes, will has no negative influence on an executive experience infertility as adults. Trans youth and functioning task indicative of healthy pubertal their families should receive counseling from both brain development. Longitudinal studies by de physicians and gender therapists regarding the Vries and her colleagues indicate early medical Current research indicates few impact on fertility of both puberty suppression interventions, including puberty suppression, adverse events associated with and gender affirming hormones, along with hormone therapy, and surgeries, lead to successful either puberty suppression or available procedures for preserving fertility psychological functioning in early adulthood. hormone therapy. options (e.g., harvest and storing oocytes, sperm However, virtually all the outcome data in cryopreservation). gender non-conforming youth have been carried out in Europe and Canada in patients starting Gender-affirming hormone therapy suppression at or older than age 12, although The use of gender-affirming hormone therapy in longitudinal studies are now being done in the adolescents has been in use since the early to mid 1990s, with the earliest United States, including in youth starting suppression at younger ages literature primarily from the Netherlands. Currently, most transgender (within Tanner 2). adolescents present for gender-affirming hormone therapy without having Significant barriers to the use of puberty suppression in Minnesota exist. undergone puberty suppression initially. While current WPATH and There are a limited number of medical providers and experienced gender Endocrine Society guidelines recommend starting hormone therapy at age therapists, most geographically clustered in the Twin Cities metro area. All 16, these guidelines allow for exceptions for youth who are well established parents/legal guardians must consent, limiting access to youth with family in their gender identity, and cognitively and emotionally mature enough conflicts. GnRH analogues are prohibitively expensive without insurance to make decisions regarding gender-affirming hormones. Both WPATH coverage for most families; insurance coverage for puberty suppression is and Endocrine Society Guidelines are in the process of revision. As with highly variable. puberty suppression, the parents/legal caregivers must provider consent if the patient is not legally able to make medical decisions for themselves (e.g., age of legal majority, emancipated minor). For patients starting gender-affirming hormone therapy after puberty suppression, GnRH analogues are continued, while estradiol or testosterone is begun in gradually escalating doses to induce a â€œnewâ€? puberty. When treatment is started after onset of puberty, without the use of GnRH analogues, hormones are often given at a higher starting dose and more rapidly increased until maintenance dosage. Secondary sex characteristics then develop accordingly, with many changes becoming increasingly irreversible over time. However, the dose and rate of bodily changes can be individualized to the gender identity, social, and psychological needs of the patient and their family. Potential side effects for gender-affirming hormones in adolescents are based primarily on evidence gained from use in adult populations. The potential effects on cardiovascular events, breast, ovarian, uterine, and prostate cancer have been studied in adults (and outlined by the Endocrine Society and WPATH), but no sufficiently longterm data exists for hormone use starting in adolescence. Testosterone therapy For trans masculine youth, testosterone therapy increases lean muscle mass, decreases subcutaneous fat, and increases male pattern body and facial hair, which are all partially reversible. Patients who were pubertally suppressed before growth plate closure may reach an adult height near normal male range. Menses are suppressed, however, this is often reversible with cessation of testosterone. Testosterone therapy alone is not adequate for contraception, even if the patient is amenorrheic. Testosterone crosses the placenta and can affect a developing fetus; adolescents will need to be counseled regarding the need for adequate contraception. Irreversible effects of testosterone include clitoromegaly and deepening of the voice.
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Early side effects of testosterone therapy include acne, and potentially androgenic alopecia. Adverse advents, more common with supraphysiologic levels, include polycythemia, dyslipidemia, transaminitis, weight gain, hypertension, and mood lability. GnRH analogues, if started prior to hormones, should be continued until gonadectomy. If patients cannot afford to maintain GnRH analogues for what may be many years, or if they have not been on these agents, higher doses of testosterone may be needed to induce or continue amenorrhea and maintain masculine characteristics. Estradiol therapy For trans feminine youth, estradiol therapy slows growth of facial and body hair, decreases lean muscle mass and increases subcutaneous body fat, decreases spontaneous erections, and softens skin, which are partially reversible. Estrogen leads to irreversible growth of breast tissue and growth plate closure, which, if not already complete, will lead to adult height closer to the normal female range. Masculine features already in place at the start of hormone therapy, such as facial bone structure, lower voice, or masculine body/facial hair, cannot be changed by feminizing hormones. Potential side effects of estrogen include increased risk for thromboembolic disease, liver dysfunction, cholelithiasis, weight gain, hypertension, and hyperprolactinemia. Estrogen therapy alone is not sufficient for contraception and adolescents should be counseled appropriately. Estradiol therapy alone is inadequate to keep endogenous testosterone levels low. GnRH analogues begun prior to hormone therapy should be continued until gonadectomy. If patients cannot afford to maintain GnRH analogues for what may be many years, or if they have not been on these agents, androgen blocking medications, such as spironolactone, may be substituted.
can help trans adolescents develop into well-functioning young adults, with improved social and psychological outcomes (see the sidebar for suggested resources). Family support is a critical element during this period, and differences among caregivers/parents and the trans youth regarding pace or type of intervention should be addressed early. Current research indicates few adverse events associated with either puberty suppression or hormone therapy, but outcomes data longer than 20 years is lacking. Physicians should continue to be involved in the sexual health of their trans adolescent patients, and provide repeated counseling regarding the impacts of hormonal interventions on fertility and contraception needs. Mental health and ongoing health maintenance remain important factors throughout any hormonal intervention, including smoking, healthy diet, and physical activity. Physicians can best support trans youth and their families by providing a gender-affirming clinical environment, assisting them in accessing gender-related services including puberty suppression and hormone therapy, and providing culturally competent primary care.
Jamie Feldman, MD, is board-certified in family medicine, and an associate professor in the Department of Family Medicine and Community Health at the University of Minnesota. She serves as faculty in the Program in Human Sexuality (PHS), a nationally and internationally recognized leader in the interdisciplinary research and treatment of sexual health concerns, including transgender health. She has presented and published extensively on transgender hormone therapy and primary care.
Talking points for physicians and families Many gender nonconforming children do not become transgender adolescents or adults. A physician can help children and families cope with stigma and nonacceptance, assist with gender exploration, and manage relationships and expectations. Referral to a mental health professional with expertise in gender is often beneficial. Puberty suppression and genderaffirming hormone therapy, especially as part of a multidisciplinary team,
SUGGESTED RESOURCES 14 H embree, Wylie C., et al. “Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline.” The Journal of Clinical Endocrinology & Metabolism 94(9) (2009): 3132–3154.
24 d e Vries, Annelou LC; Klink, Daniel; and Cohen-Kettenis, Peggy T. “What the Primary Care Pediatrician Needs to Know About Gender Incongruence and Gender Dysphoria in Children and Adolescents.” Pediatric Clinics of North America 63(6) (2016): 1121–1135.
34 Bonifacio, Herbert J and Rosenthal, Stephen. “Gender Variance and Dysphoria in Children and Adolescents.” Pediatric Clinics of North America 62(4): 1001–1016.
MINNESOTA PHYSICIAN MAY 2017
Telemedicine today An expanding range of applications BY NICK HERNANDEZ, MBA, FACHE
way you will be less likely to overspend or purchase equipment you don’t need or can’t use. In this article, we will cover:
elemedicine helps eliminate distance barriers and can improve access to medical services that are often not consistently available in distant rural communities. Many practices are becoming increasingly interested in how such a program could be implemented into their operations. Physicians often want to start a telemedicine program quickly, however, practice managers don’t want to learn about telemedicine through trial and error. They prefer to ramp up more slowly.
• Consumer-driven acceptance
Often, the biggest issue for practices is that they immediately want to focus on the technology. This often leads to two problems: 1) they either become overwhelmed by the amount of options available and end up not pursuing telemedicine, or 2) they choose poorly and the technology is quickly abandoned. When investigating whether to start a telemedicine program, it’s best to put off studying the available technology until later in the decision-making process. There are many more important things to consider in order to end up with a successful telemedicine program, and this
• Legal requirements • Reimbursement • Security • Market analysis • Feasibility study
Millions of Americans report that smartphones and apps have changed the way they manage their health and wellness. As Americans begin to use wearable devices to track and collect their personal health data, there will be more willingness to share that data with health care providers and intermediaries. The 2015 Digital Impact Survey by Apigee Institute demonstrated that 80 percent of smartphone owners expect a doctor to offer key services via apps either now or within the next one to two years. That same survey showed that 28 percent of millennials would prefer a doctor who incorporates apps and fitness tracker data as a regular part of their practice. Other reports show an increased adoption of connected health devices that include items such as blood pressure meters, connected treadmills, digital fitness trackers, and networked weight scales. A 2016 study by Parks Associates (a market research company) found that 42 percent of consumers aged 24–34 own a connected health device compared with 37 percent of consumers aged 18–24 and 31 percent of consumers over the age of 65. These large numbers demonstrate the oncoming wave of telehealth demand and people’s acceptance of this kind of virtual care.
Legal requirements Because of the current fragmented adoption of telemedicine in the U.S., practices must look into a host of legal requirements, especially as those requirements pertain to applicable state law. Generally, physicians must be licensed in the state where the treatment or diagnosis is being provided. Many malpractice insurers now cover telemedicine, but you should discuss your plans with your insurance carrier so they can look at the various risks involved. As with other areas of health care, privacy, consent, and regulatory compliance must be thoroughly evaluated by a health care attorney. In addition, you should have your proposed telemedicine program reviewed by a telemedicine consultant and health care attorney to ensure that it is vetted to avoid potential fraud and abuse laws. Minnesota’s telemedicine parity law In 2015, Minnesota lawmakers enacted a telemedicine parity law (see Chapter 71—S.F.No. 1458) that enhances coverage and payment under private insurance and Medicaid. Under the law, commercial plans cannot charge a higher deductible or co-pay for telemedicine services. The
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Minnesota Department of Human Services approved guidance enforcing attestation requirements and reimbursement for telerehabilitation services provided by speech-language pathologists/assistants, physical therapists/ assistants, occupational therapists/assistants, and audiologists. Medicaidenrolled fee-for-service providers may bill for eligible services using either GT or GQ modifiers (consult with your billing staff) when a patient is located at an eligible original site. Both the home and school are considered eligible originating sites. Here are some key points regarding the legal aspect in Minnesota Eighty percent for physician practice standards and licensure: • Requirements for telemedicine are on par with requirements for in-person services, not including prescribing. No unique practice standard requirements are needed for telemedicine.
o A telepresenter (usually a nurse trained in the technology who can facilitate exams under physician guidance) is required on premises with the patient. •T he Chemical Dependency Continuum of Care Pilot Project implemented in 2013 (see Chapter 254B, Section 14) improved access to treatment and recovery support for alcohol and drug abuse services.
Security Most physician groups and hospitals are well versed and compliant with government regulations for securing patient data (e.g., HIPAA, business associate agreements, etc.). Furthermore, with the adoption of electronic health records and patient portals, both providers and venders are aware of safeguards that need to be in place. Consequently, the implementation of a telemedicine program follows suit with all of the above. Perhaps a key differentiator though is when pursuing a provider-to-patient telemedicine engagement. To be clear, when communicating with patients for telemedicine purposes, there are risks that the telemedicine encounter itself could result in privacy or security law violations. Because telemedicine services, by definition, involve communications with patients who are not physically present, there is a
of smartphone owners expect a doctor to offer key services via apps.
• A qualifying out-of-state physician has the option of applying for a full license or a telemedicine permit to practice in Minnesota. • Minnesota’s Board of Medical Practice has a policy statement on internet prescribing.
Reimbursement assessment Currently, reimbursement (governmental and commercial) continues to be a barrier to telemedicine adoption in some (but not all) states. The type of telemedicine services you are interested in as well as the type of setting needs to be examined through the lens of the state(s) where services will be rendered, as well as the portfolio of applicable payers. Even though there may be restrictions that affect billing practices (and thus reimbursement), there are ways to get “paid” (e.g., subscriptions, etc.) for telemedicine services in lieu of reimbursement. Here are some key points regarding coverage and reimbursement in Minnesota:
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• Minnesota’s telemedicine parity law affects private insurers and state employee health plans, including dental and joint self-insured plans. • Regarding Medicaid: o N ew policies included in the parity law impose attestation requirements before payment is made for telemedicine. o Coverage for interactive audio-video and store-and-forward. o Distant site providers are limited to a set of providers including OT, PT, speech therapists, and audiologists. Providers are not required to be located in a medical facility. o Medicaid also places frequency limits on all covered telemedicine services. o Minnesota Medicaid now covers dental and alcohol and substance abuse services via telemedicine under the physician services benefit. o Skilled nursing and the cost of remote patient monitoring (RPM) equipment rental is covered under the home health benefit.
MINNESOTA PHYSICIAN MAY 2017
Infant brain development and autism A breakthrough in early identification BY JED ELISON, PHD
he economic and psychological burden of caring for and educating an individual with autism spectrum disorder (ASD) is substantial. According to estimates published in JAMA Pediatrics in 2014, lifetime care costs for an individual with autism are $1.4–$2.4 million greater than costs associated with rearing and caring for a typically developing child. In the United States, aggregated national costs for children and adults with autism approximate $240 billion, annually. Early behavioral intervention significantly improves developmental outcomes for individuals with autism and reduces lifetime costs. However, early identification and early diagnosis remain enduring challenges. Indeed, the average age of diagnosis in the state of Minnesota is approximately five years of age.
Improving early identification How do we approach the challenge of improving early identification? A number of researchers focused on comprehensively characterizing children around the time of an early diagnosis (18–30 months of age), which informed speculation about potential early behavioral markers that might be apparent at six, 12, or 15 months. But we needed more than “informed” speculation.
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The simplest approach was to ask parents about their child’s development that preceded a diagnosis. This approach has value but also various limitations. In a similar vein, researchers collected home movies (many targeted first year birthday parties) in the search for early behavioral markers. This approach too, proved meaningful, but quite difficult to experimentally and systematically control. We needed to identify a “risk factor” that would enable prospective evaluation of children prior to and across the time interval when first concerns are generally reported.
The sibling recurrence rate The estimated sibling recurrence rate of autism is between 10–20 percent. Compared with the 1–2 percent prevalence estimates in the general population, this was precisely the leverage the field needed. If we could evaluate enough infant siblings of children with autism, a proportion of them would develop autism themselves. We could then go back into their data and identify behavioral features that differentiated them from their high-risk peers who did not develop autism. The “infant-sib” paradigm offered great promise for early identification efforts that we assumed would have direct clinical implications. But we also hoped that characterizing the timing of neurobiological changes that precede an autism diagnosis might inform new models of pathogenesis.
I was a graduate student in 2007 at the University of North Carolina when In the Feb. 16, 2017 issue of Nature, my colleagues and I published brain my mentor received an Autism Centers of Excellence grant from NICHD (Eunice development results from the IBIS Network. Brain structure was measured with Kennedy Shriver National Institute of Child Health and Human Development) magnetic resonance imaging (MRI) during natural sleep, either around a daytime to initiate the Infant Brain Imaging Study (IBIS Network) (http://www. nap or bedtime. The primary risk associated with this method is hearing damage ibis-network.org/). There are four data collection sites around the country: from the loud MRI sounds, but as the loud noises would wake a sleeping infant, 1) University of North Carolina–Chapel Hill, we do an excellent job attenuating the noise levels so 2) Children’s Hospital of Philadelphia, 3) University of that the infant/toddler sleeps naturally. We observed Washington, and 4) Washington University in St. Louis. an accelerated rate of cortical surface area expansion The study objectives were to collect behavioral and brain between six and 12 months in infants later diagnosed According to estimates ... imaging data from a large number of high-risk infant with autism. This surface area expansion was followed lifetime care costs siblings and low-risk comparison infants at six, 12, and 24/36 by an increased rate of total brain volume growth for an individual with autism months of age. Now, as a faculty member at the University between 12 and 24 months in these children. The are $1.4–$2.4 million. of Minnesota, I am a co-investigator on the project. rate of brain volume growth between 12–24 months significantly predicted social impairments measured Brain development at 24 months of age. While characterizing the timing In the past 10 years, we have learned a great deal about and pattern of brain development in infants across this behavioral development in high-risk infant siblings of period is important—what are the clinical implications? children with autism. Notably, there are no overt behaviors or behavioral profiles that distinguish six month olds who later develop autism from six month olds who Classifying diagnostic outcomes do not. But by 12 months of age a number of risk markers differentiate children Next, we selected hundreds of brain structure measurements (156 at 6 who develop autism from those who do not (e.g., inconsistently responding to one’s months and 156 at 12 months to be precise) and used an artificial intelligence name, diminished response to bids for shared attention, diminished spontaneous algorithm called deep learning to determine whether we could accurately gaze to the face to extract social information, and inconsistently making eye classify individual diagnostic outcomes. The algorithm proved sensitive, contact). However, group differences don’t necessarily translate into individual correctly classifying 30 out of 34 children (88 percent) with ASD, and level prediction, and we have not yet identified a set of behavioral features at 12 specifically, correctly classifying 138 out of 145 high-risk children (95 percent) months that predict a later diagnosis with suitable specificity and sensitivity. But Infant brain development and autism to page 364 these data beg the question, what is happening between six and 12 months of age?
MINNESOTA PHYSICIAN MAY 2017
3Infant brain development and autism from page 35 who did not receive a diagnosis at 24 months. Overall, the classification was 94 percent accurate. After a bit more digging, we learned that the most important distinguishing features were measures of surface area at six months of age. As scientists, we know that these findings need to be replicated. We also need to determine that the algorithm will perform on different neuroimaging platforms (updated MRI scanners) and with updated neuroimaging acquisition sequences. It is also important to reiterate that the findings may be specific to “multiplex” families—or families who have one or more affected child. At this point in time, we do not envision this approach as a feasible “screener” for the general population. We are actively searching for less expensive “surrogate procedures” that could be implemented with the general population. Further, we need to flesh out the ethical, legal, and social implications of this type of pre-symptomatic predictive information. How do we communicate this type of “risk” to parents and what can we do for them?
Further studies If we are able to replicate and extend these findings, we may well be less than 10 years away from the first prevention trial for autism. There are two examples in the literature of small-scale intervention trials with high-risk infant siblings (selected on no other features other than being a younger sibling of a child with autism) showing positive outcomes. These behavioral interventions have been implemented in seven to 15 month olds. There are also a couple of behavioral interventions designed for approximately 18 to 24 month olds that could be readily downward extended. But as the readers will fully appreciate, this will take substantial economic and societal investment.
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The potential to arrest, attenuate, or mitigate abnormal brain development with intensive behavioral intervention prior to the consolidation of a diagnostic behavioral profile has far reaching implications. While the six to 15 month time period represents a time of vulnerability for high-risk infants, this is also a time of opportunity to leverage the plasticity or malleable of the developing brain. Families participate in our studies because they get the best developmental monitoring for their infant. We provide clinical feedback and clinical service recommendations if warranted after each visit. What if we could offer more than monitoring/surveillance? A cadre of young researchers is positioning the University of Minnesota to lead the next iteration of these studies. I am currently leading an unprecedented study of brain development in typically developing children between birth and five years of age using cutting-edge technology developed by my colleagues at the Center for Magnetic Resonance Research. This study, the Baby Connectome Project (http:// babyconnectomeproject.org/), will not only elucidate patterns of structural and functional connectivity with the highest resolution to date, but will function as a springboard for developing our own “infant-sib” study in the near future. While I have focused on our early identification work, a number of my colleagues at the University of Minnesota are working on developing novel, evidence-based intervention programs for individuals with autism and other intellectual and developmental disabilities across the lifespan. The science of autism has made great strides in the past 20 years—but there is more work to tackle tomorrow. Jed Elison, PhD, is a McKnight Land-Grant Professor with the Institute of Child Development and Department of Pediatrics at the University of Minnesota.
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3Telemedicine today from page 33 heightened risk of disclosing information to the wrong individual (i.e., somebody who is not the patient). This would likely be an unauthorized disclosure as defined by HIPAA. To minimize this risk, physician groups and hospitals should have in place reliable methods for verifying and authenticating the identities of the patient and practitioner at the beginning of each telemedicine encounter.
educate you about telemedicine technology applications that may apply to your potential goals, as well as educate you about predictors of success and best practices.
The implementation of telemedicine services to your existing practice will certainly impact your operations. Some items to consider are the time saved by implementing telemedicine, how your telemedicine program ties into your regular in-person practice, and what type It is advisable for physician groups and of clinic hours you will devote to telemedicine. There is no such thing hospitals to adapt their privacy and security There is no such thing as a standard telemedicine as a standard practices in response to the specific privacy program. Consequently, it is extremely important telemedicine program. risks and compliance challenges associated to take the time to develop a telemedicine strategic with telemedicine. Depending on the nature of plan first, as there are many nuances to consider the telemedicine services being provided, this as they relate to your particular practice. Hiring a may require updating policies and security risk consultant to help guide you in the right direction analyses, and taking a more active compliance will be money well spent, especially given that role in the coordination of telemedicine services with outside organizations. such an endeavor will change your practice operations, including your marketing and financial operations. Market analysis Telemedicine has many applications and uses, so your first task is to determine what the needs of your patients are and how telemedicine can address them. This step is a very detail-oriented process (e.g., competitive forces, SWOT analysis, market demographics, etc.) that will help identify potential telemedicine opportunities. A qualified consultant will help
MAY 2017 MINNESOTA PHYSICIAN
Nick Hernandez, MBA, FACHE, is CEO and founder of ABISA, an independent consultancy specializing in strategic growth initiatives (www.abisallc.com).
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3Guidelines for care transitions from page 25 patients’ health and health habits outperformed other primary care clinics and saved Minnesota more than $1 billion over five years.” Integrated Health Partnership Building on PCMH, Minnesota created the Integrated Health Partnership (IHP), which was designed to create a shared-risk arrangement to improve care coordination and quality for Medicaid recipients. In order to become an IHP participant, a provider must:
Conclusion While the care transition approaches of ASPIRE, ACOs, PCMHs, and IHPs may be slightly different, they share several common traits. All stress looking at the whole person needs of the individual, partnering with other organizations in the community, and innovating to address complex issues impacting the health of low income populations.
Health care payment policy is constantly changing and, in the current environment, Finding better ways organizations and providers cannot know which to provide care to those with way the tide will turn. The Healthcare Financial the fewest resources will likely Management Association (HFMA) points out become an expectation. • Deliver the full scope of primary care that ongoing directives to increase quality while services. decreasing cost are not likely to go away. Finding • Coordinate with specialty providers and better ways to provide care to those with the fewest hospitals. resources will likely become an expectation, at least of CMS. And finally, as noted in the StarTribune, those systems that • Demonstrate how they will partner with community organizations demonstrate value-based care coupled with innovative approaches will have and social service agencies and integrate their services into care the best chance of success in the future. delivery.
In return for participation, cost savings are shared. According to a presentation by Mathew Spaan, policy analyst and IHP lead with the Minnesota Department of Human Services, in 2014, the nine participating providers received shared savings settlements totaling $22.7 million. Requests for proposals can be found on the Minnesota Department of Human Services website at http://bit.ly/2oPSWdc
MAY 2017 MINNESOTA PHYSICIAN
Ann Fiala, RN, BSN, CPHRM, CHC, is a senior claims consultant at Coverys. She has more than 30 years of health care experience with extensive experience in medical staff credentialing, regulatory readiness, patientcentered care, utilization and case management, and data analytics.
MINNESOTA PHYSICIAN MAY 2017
3Off-label prescribing from page 17 P. Aaron Basilius of McGuire Woods, recommend that physicians follow four criteria when prescribing off-label to ensure that they are abiding with applicable laws and statutes. The provider should ensure that: 1.
The patient is aware of the fact that he or she is prescribing off-label.
2. Their principal motivation is to directly benefit the health and well-being of the patient for whom the medication is prescribed. 3. Their medication choice is based on their own expert opinion and based on reputable peer-reviewed literature.
Jason Varin, PharmD, is an assistant professor in the department of
of Pharmacy. He has practiced as a clinical community pharmacist for 25
The decision would generally be supported by his or her peers.
If the prescriber considers and acts within these four principles and they are acting solely in the interest of a single patient, the possibility of being taken to court and being sued successfully for malpractice in prescribing a drug off-label, is significantly diminished.
Conclusion The major role of labeling is to provide the physician with the results of the studies conducted by the manufacturer regarding efficacy and safety of a product. This information is obtained by performing phase I, II, and III trials in humans plus animal studies used to obtain an IND to perform the human studies. The human studies are performed under controlled conditions and do not account for the variability that is encountered in practice. Thus the doses indicated in the label may be too low for some
patients and dosing off label is necessary in some circumstances. Indications are usually obtained for specific medical diagnoses, but often patients report effects that differ from the specific indication. Many drugs initially approved for one condition have found uses different than the original indication, but because of the cost of performing studies for the new uses, approval is often not sought for these conditions. Support for off label uses that have support in literature is appropriate. Too strict application of labeling limitations in many cases may not be the best practice.
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Pharmaceutical Care and Health Systems at the University of Minnesota College years and currently teaches in the experiential program, and interprofessional collaboration and communication.
Ilo Leppik, MD, is a professor of pharmacy and neurology at the University of Minnesota Academic Health Center. For the last 40 years, his practice has been focused on treating people with epilepsy and his research has been centered on developing new treatments for people with seizures. *Special thanks to the Center for Leading Healthcare Change Student Leadership Fellows (CLHC SLFs) and fellow authors of this article: Grace Baek, Derek Borkowski, Callahan Clark, Prosperity Eneh, Gabriel Johnson, Anjoli Punjabi, Richard Shneur, Michelle Tran, and David Vermeulen.
I CAN DO ADVENTURE The approaching holiday season is about hope, magic and miracles. So too, is Diveheart. The Downers Grove-based not for profit organization provides hope, magic, and even miracles, to individuals with disabilities. Diveheart offers children, veterans and others with disabilities the opportunity to escape gravity through Scuba Therapy. Diveheart participants include individuals with virtually any type of disability including Down syndrome, autism, cerebral palsy, paraplegia, blindness, deafness, spinal cord injuries, traumatic brain injury, post-traumatic stress disorder and more.
HOPE The Diveheart vision is to unleash the unrealized human potential that often exists in individuals with disabilities. The confidence, independence and self-esteem realized by Diveheart participants is tremendous. Diveheart helps individuals focus on what they can do, rather than what they can’t do. MAGIC Diveheart Scuba Therapy helps participants focus on their abilities, rather than their disabilities. This helps them to take on challenges that they may never have taken on before. Furthermore the forgiving, weightless environment of underwater offers buoyancy and balance to individuals who might struggle on land. They’re often able to move in ways that are impossible before joining a Diveheart program. Zero gravity is the great equalizer. MIRACLES Diveheart participants have experienced improved range of motion, ability to focus, pain relief and more. The aspect of pressure while diving provides benefits for people with autism and chronic pain due to spinal cord injuries. Some tell us that after diving, they’re pain free for up to three weeks, often for the first time since their injury. Every one is able to help perpetuate hope, magic and miracles during the holiday season. Your donation helps to make it possible for individuals with disabilities to experience Scuba Therapy, and the resulting benefits so that they might “Imagine the Possibilities” in their lives. Please visit www.diveheart.org/donate/ to learn more about how you can help promote the hope, magic and miracles of Diveheart. Diveheart donations are also accepted at 900 Ogden Ave #274 Downers Grove, Illinois 60515. Jim Elliott Founder & President Diveheart
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