Diabetes

Key Points

  • Diabetes mellitus is a group of metabolic diseases  that lead to high levels of blood glucose (hyperglycemia), which is caused when the body does not make any or enough insulin, or does not use insulin well.
  • Because diabetes is a relatively common condition, practicing dentists are likely to encounter it frequently.
  • Type 1 diabetes is a chronic autoimmune disease in which the beta cells in the pancreas create little to no insulin, and accounts for 5% to 10% of all diabetes cases. In contrast, Type 2 diabetes accounts for 85% to 90% or more of diabetes cases and is one of the commonest chronic diseases, characterized by decreased response of target tissues to insulin, dysregulation of insulin production, or a combination of both.
  • As with any patient, the dentist should review the patient’s medical history, take vital signs, and evaluate for oral signs and symptoms of inadequately controlled diabetes, which may be common. Oral manifestations of uncontrolled diabetes can include: xerostomia; burning sensation in the mouth; impaired/delayed wound healing; increased incidence and severity of infections; secondary infection with candidiasis; parotid salivary gland enlargement; gingivitis; and/or periodontitis.
  • Although patients with diabetes usually recognize signs and symptoms of hypoglycemia and self-intervene before changes in or loss of consciousness occurs, staff should be trained to recognize the signs and treat patients who have hypoglycemia.  In such cases, a glucometer should be used to test patient blood glucose levels, and every dental office should have a protocol for managing hypoglycemia in both conscious and unconscious patients.
Introduction
Diabetes mellitus is a group of metabolic diseases that leads to high levels of blood glucose and is caused when the body does not make any or enough insulin, or does not use insulin well.1 In 2012, it was estimated that 29.1 million people in the U.S. (i.e., 9.3% of the population) had some form of diabetes; of these, the disease was undiagnosed in 8.1 million people, meaning that almost 28% of people with diabetes were undiagnosed.1, 2 Because diabetes is a relatively common condition, practicing dentists are likely to encounter it frequently.3

Disease Description
Classification.  Classification of diabetes is based on the pathogenic processes that can lead to either absolute or relative lack of insulin, resulting in hyperglycemia (high blood glucose).3 Insulin is a hormone produced by pancreatic beta islet cells, which is needed for the uptake of blood glucose by cells to produce energy. When there is a lack or absence of insulin, or when cells are insensitive to its actions, a high circulating level of blood glucose results (i.e., hyperglycemia).3 Although there are various causes for less common types of diabetes, including drug- or chemical-induced diabetes, exocrine pancreatic disease, or infections (e.g., cytomegalovirus), the two most common subtypes of diabetes are known as Type 1 or Type 2 diabetes.3

Type 1 diabetes, formerly known as juvenile diabetes, is a chronic autoimmune disease in which the beta cells in the pancreas create little to no insulin3, 4 and accounts for 5% to 10% of all diabetes cases.3 Autoimmune destruction of beta cells is the most common cause, although any loss of pancreatic tissue (e.g., pancreatitis, surgical removal of the pancreas) can lead to insulin dependence.3 Type 1 diabetes is generally diagnosed in younger individuals (usually younger than 25 years of age) and has a strong genetic predisposition.3 Exogenous insulin is needed to regulate blood glucose levels in people with Type 1 diabetes.3

In contrast, Type 2 diabetes accounts for 85% to 90% or more of diabetes cases and is one of the most common chronic diseases, as well as one of the leading causes of death and disability in the U.S.5 Type 2 diabetes is characterized by decreased response of target tissues to insulin, requiring increasing levels of insulin for an adequate response, dysregulation of insulin production, and insulin resistance.3 Type 2 diabetes is associated with excess weight, physical inactivity, family history of diabetes, and certain ethnicities.4 Although some people with Type 2 diabetes can help improve their glycemic control with diet, exercise, and weight loss, patients may require insulin sensitizers that help peripheral tissues take up glucose (i.e., biguanides [metformin] or thiazolidinediones) or oral hypoglycemic agents that either stimulate release of insulin (i.e., insulin secretagogues such as sulfonylureas).3

Another type of diabetes is gestational diabetes, a state of glucose intolerance that occurs in pregnant women who don’t otherwise have diabetes.3 Occurring in the second half of a pregnancy, gestational diabetes is caused by placental hormones and results in insulin resistance and relative insulin deficiency.3 Although true gestational diabetes resolves during the postpartum period, those who have had gestational diabetes are at increased risk of in developing Type 2 diabetes later in life.3

The term “prediabetes” is used when blood glucose levels are higher than normal, but not high enough for a formal diagnosis of diabetes.4 Prediabetes means a person is at increased risk for developing Type 2 diabetes, as well at increased risk for heart disease and stroke.4  Although lifestyle modification involving weight loss and engaging in moderate physical activity can help people with prediabetes delay or prevent the onset of Type 2 diabetes,4 it is estimated that as many as 90% of those with prediabetes are unaware that they have prediabetes.6 Assessment of risk for prediabetes can be conducted using printed or online versions of a seven-item questionnaire available through the American Diabetes Association, Centers for Disease Control and Prevention, and American Medical Association (links available in the "Other Resources" section).

Symptoms/Diagnosis.
  Initial symptoms of diabetes include increased thirst and urination. Other symptoms can include unexplained weight loss, fatigue, blurred vision, increased hunger, and sores that do not heal.

Blood tests are generally used in the diagnosis of diabetes and prediabetes.4  Tests used include measurement of hemoglobin A1c, which is a measure of glycosylation of the hemoglobin molecule, fasting blood glucose measurement, and/or an oral glucose tolerance test.4  The American Diabetes Association provides recommendations for classification and diagnosis of diabetes.

Complications.  Over time, individuals with diabetes sustain progressive damage to nerves and blood vessels due to elevated levels of circulating glucose, which can increase the incidence and severity of complications such as heart disease, stroke, kidney disease, blindness, dental disease, and amputations.4 Additionally, diabetes may increase susceptibility to other diseases, impair mobility, contribute to depression, and cause problems during pregnancy.4

Glucose Control
Three common complications that can occur when glucose levels are not well controlled are hypoglycemia, hyperglycemia and diabetic ketoacidosis.

Hypoglycemia.  Hypoglycemia is a condition in which blood glucose levels drop below normal. For many people with diabetes, this means a blood glucose level of 70 milligrams/deciliter (mg/dL) or less.7, 8 Hypoglycemia also may be referred to as “insulin shock” or “insulin reaction.” Untreated hypoglycemia can result in unconsciousness, coma or death.

Several situations can lead to hypoglycemia:7
  • Adverse effect of insulin or other diabetes medications;
  • Disruption in food intake (timing of a dental appointment, illness/nausea, vomiting, diarrhea, skipping or delaying a meal, etc.);
  • Drinking too much alcohol for the amount of food being eaten;
  • An unexpected/unplanned increase in physical activity.

Symptoms.  Symptoms of hypoglycemia may include changes in mental state or emotions, or physical symptoms.

 Symptoms of Mild-to-Moderate Hypoglycemia7

 Shakiness

 Sweating

 Fast or irregular heartbeat

 Dizziness or lightheadedness

 Hunger

 Nervousness

 Change in behavior or personality

 Tingling or numbness of the lips or tongue

 Sleepiness

 Blurred vision

 Loss of coordination

 Headaches

 Weakness

 Trouble concentrating, confusion

 Paleness

 Irritability

 Argumentative, combative

 Symptoms of Severe Hypoglycemia7
 Unable to eat or drink

 Seizures or convulsions

 Unconsciousness

Treatment.  If hypoglycemia is suspected, immediate treatment should be implemented.

  • Check the patient’s blood glucose levels using a glucometer. Levels that are ≤70 mg/dL indicate hypoglycemia.  
  • Provide the patient with 15-20 grams of oral carbohydrates to eat or drink, such as:7, 8
    • 4 glucose tablets or one tube of glucose gel;
    • ½ cup of fruit juice* or regular (non-diet) soda;
    • 1 tablespoon of sugar, honey or corn syrup;
    • 8 ounces of non-fat or 1% milk;
    • Hard candies, jelly beans or gumdrops;
    • 2 tablespoons of raisins.

(*NOTE:  People who have concomitant kidney disease should not drink orange juice for their 15 grams of carbohydrates because of the high potassium content.Apple, grape, or cranberry juice cocktail are good alternatives.)

  • Wait 15 minutes, then check blood glucose levels again.
  • Repeat these steps until blood glucose levels are above 70 mg/dL.

In severe cases, hypoglycemia can cause unconsciousness, seizures or coma. If the dental patient is not awake and/or unable to eat or drink, emergency medical help should be summoned.  Injectable glucagon, available by prescription, signals the liver to release glucose into the bloodstream, and can help restore blood glucose levels to normal in emergencies.  Glucagon may be administered while waiting for help to arrive.9

Hyperglycemia.  Hyperglycemia occurs when blood glucose levels are abnormally high.  This can occur anytime there is not enough insulin in the bloodstream or the body is not using insulin properly.

Several conditions can lead to hyperglycemia (e.g., pancreatitis, Cushing’s syndrome, pancreatic cancer, adrenal hormone insufficiency), but it is a primary symptom of diabetes.  Untreated hyperglycemia can damage the cardiovascular, circulatory or nervous systems, the kidneys or vision.10 It can also result in slowed wound healing. In more serious cases, extreme or prolonged hyperglycemia, can cause a life-threatening condition called ketoacidosis (see below for further discussion).

A number of circumstances can lead to hyperglycemia in people with diabetes:11
  • Low insulin levels, which can occur either when insufficient insulin is used (e.g. miscalculation in the amount injected or an insulin-pump malfunction) or when insulin is not used efficiently by the body;
  • Eating more than planned or exercising less than planned according to the amount of insulin taken;
  • Stress, either physical (e.g., illness-related or medical/dental procedure-related) or emotional (e.g., conflict, personal loss).

Symptoms. Symptoms of hyperglycemia include:
  • high levels of sugar in the urine;
  • frequent urination;
  • increased thirst;
  • fatigue;
  • blurred vision.

Treatment.  Lifestyle changes, like increased exercise or eating a healthy, well-proportioned diet,12 may help control hyperglycemia. (NOTE: People with diabetes whose glucose level is above 240 mg/dL should check their urine for ketones.  If ketones are present, they should not exercise and should consult their physician for other ways to reduce their blood sugar levels.11)  If these changes don’t help resolve hyperglycemia, a physician may recommend adjusting current medications or prescribing new or additional medication to better manage glucose levels.

Diabetic Ketoacidosis.  Diabetic ketoacidosis is a serious condition that can develop when there is not enough insulin to help the body adequately use glucose.

Diabetic ketoacidosis develops when the balance between glucose and insulin levels is not well controlled.  The body typically metabolizes glucose to generate energy.  When insulin levels are too low, the body begins to break down fat cells for energy instead, which results in the production of acidic ketones in the blood. Buildup of ketones in the blood can be toxic.

Without intervention, which usually must be done in a hospital, coma or death can occur.13

Symptoms.  The following symptoms may indicate diabetic ketoacidosis:13
  • breath that smells fruity;
  • very dry mouth;
  • high blood glucose levels;
  • high levels of ketones in the urine;
  • frequent urination;
  • shortness of breath;
  • constant tired feeling;
  • dry or flushed skin;
  • nausea, vomiting or abdominal pain;
  • difficulty concentrating or confusion.

Treatment.  If ketoacidosis is suspected, the symptomatic person should be taken to the nearest emergency room or that person’s physician should be immediately contacted.13

Monitoring Glucose Levels.  Blood-glucose levels can be checked chairside using a drop of blood. Glucometers designed for use in a variety of settings, such as nursing homes, health fairs or dental clinics, are available by prescription. Because they are intended for use by multiple individuals, they are designed to facilitate thorough cleaning and disinfection between uses to help prevent the spread of bloodborne pathogens.14  After each use, the device must be cleaned and disinfected according to the manufacturer’s instructions.14, 15

Staff should be familiar with glucometer use to help avoid errors that could affect the reading such as improper use, problems with the device or reagents used with the device, or environmental problems like lighting.14  Inaccurate readings may occur when the blood sample is too small; taken from a site not intended by the manufacturer; not properly applied to the strip; or contaminated.

Periodontal Disease and Diabetes
Periodontal disease is commonly seen in people with diabetes,16-18 and is considered a complication of diabetes.3, 16, 17, 19, 20 Interestingly, the relationship between diabetes and periodontal disease is seen to be bidirectional, meaning that hyperglycemia affects oral health while periodontitis affects glycemic control (e.g., increased HbA1c).18, 20-22 Research also suggests that periodontitis is associated with poor glycemic regulation,3, 17, 22 but the evidence is inconsistent,16, 17 particularly in patients with type 1 diabetes.19, 22 Most research indicates an association between periodontal disease and increased risk of diabetes-related complications.19, 21, 22

A 2018 systematic review and meta-analysis update of a 2012 review confirmed findings that periodontitis is associated with (1) higher HbA1c levels in persons without diabetes and persons with type 2 diabetes, (2) worsened complications from diabetes in people with type 2 diabetes, and (3) a higher prevalence of complications in persons with type 1 diabetes.19 The study also found that periodontitis is associated with higher prevalence of prediabetes, and that severe periodontitis is statistically significantly associated with an increased risk of developing diabetes.19

Diabetes and smoking are both considered risk factors for periodontitis.23, 24 There is some evidence that smoking and diabetes may have a synergistic effect, although the mechanism(s) responsible are unclear as changes to the oral microbiome,23 inflammatory response, and even periodontal health25 are not consistently reported to be altered when comparing people with diabetes who do and do not smoke.26

Periodontal Treatment and Glycemic Control
There is inconsistent, but suggestive, evidence that periodontal treatments, including scaling and root planing, may result in improvement of glycemic control.17, 21, 22, 27-29 A 2018 systematic review of observational studies found “insufficient evidence to evaluate the impact of periodontitis on glycemic control” in persons with type 1 diabetes, but that periodontitis is associated with higher HbA1c and worse diabetes-related complications in persons with type 2 diabetes.19 A 2018 systematic review of meta-analyses of randomized controlled trials (RCTs) reaffirmed earlier findings that periodontal treatment (i.e., scaling and root planing) significantly reduces HbA1C levels at 3 months, with even more reduction after 6 months.28 Results from RCTs, however, are not entirely consistent: a 2013 study of patients with type 2 diabetes found no improvement in glycemic control following periodontal therapy,30 and a 2018 study found no significant change in glycemic control in patients with Type 1 or Type 2 diabetes.31 Despite lack of a consensus on treatment outcomes in controlling glycemic levels, it is generally agreed that patients with diabetes benefit from periodontal therapy in conjunction with good oral health maintenance at home.20-22, 32

Dental Considerations for People with Diabetes
Diabetes can arise in individuals at any age. As with all patients, the dentist should review the patient’s medical history, take vital signs, and evaluate for oral signs and symptoms of inadequately controlled diabetes, which may be common.33 Oral manifestations of uncontrolled diabetes can include xerostomia, burning sensation in the mouth (which may possibly be related to neuropathy), impaired/delayed wound healing, increased incidence and severity of infections, secondary infection with candidiasis; parotid salivary gland enlargement; gingivitis and/or periodontitis.16, 33

Key questions a dentist may want to ask a patient with diabetes follow:33
  • How old were you when you were diagnosed with diabetes and what type of diabetes do you have? How long has it been since the diagnosis?
  • What medications do you take?
  • How do you monitor your blood sugar levels?
  • How often do you see your doctor about your diabetes? When was your last visit to the doctor?
  • What was the most recent HbA1c (A1C) result?
  • Do you ever have episodes of very low (hypoglycemia) or very high blood sugar (hyperglycemia)?
  • Do you ever find yourself disoriented, agitated, and anxious for no apparent reason?
  • Do you have any mouth sores or discomfort?
  • Does your mouth feel dry?
  • Do you have any other medical conditions related to your diabetes, such as heart disease, high blood pressure, history of stroke, eye problems, limb numbness, kidney problems, delays in would healing, history of gum disease? Please describe.

In general, morning appointments are advisable in patients with diabetes since endogenous cortisol levels are typically higher at this time; because cortisol increases blood sugar levels, the risk of hypoglycemia is less.34  For patients using short- and/or long-acting insulin therapy, appointments should be scheduled so they do not coincide with peak insulin activity, which increases the risk of hypoglycemia.34  It is important to confirm that the patient has eaten normally prior to the appointment and has taken all scheduled medications.34 If a procedure is planned with the expectation that the patient will alter normal eating habits ahead of time (e.g., conscious sedation), diabetes medication dose may need to be modified in consultation with the patient’s physician.34  Patients with well-controlled diabetes can usually be managed conventionally for most surgical procedures.33 If the patient’s food consumption will be affected after oral or dental surgery, a plan to balance the patient’s diabetes medications and food intake should be established in advance.33

Dentists should err on the side of caution when treating patients with marginally or poorly controlled diabetes.  Exercising good clinical judgment is essential because, in some situations, elective dental treatment may need to be delayed  until the patient’s diabetes is considered stable or better controlled.33 Dental implants can be placed in patients with well-controlled diabetes, and possibly in those with moderately controlled disease. However, implant placement in patients with poorly controlled disease has an unpredictable prognosis and, if possible, should be avoided.33, 35

Coordination with the patient’s physician may be necessary to determine the patient’s health status and whether planned dental treatment can be safely and effectively accomplished.33 Physicians should make laboratory test results available to the dentist upon request, and inform the dentist of any diabetic complications of relevance to the individual patient prior to dental procedures.33  The physician may need to adjust the patient’s diabetes medication to help ensure sustained metabolic control, before, during, and after surgical procedures.33

Emergency Management.  Although patients with diabetes usually recognize signs and symptoms of hypoglycemia and self-intervene before changes in or loss of consciousness occurs, they may not.3 Staff should be trained to recognize the signs (e.g., unusual behavior or profuse sweating in patients who have diabetes) and treat patients who have hypoglycemia; a glucometer should be used to test patient blood glucose levels.3 Every dental office should have a protocol for managing hypoglycemia in conscious and unconscious patients.3 Having snack foods or oral glucose tablets or gels available, especially in practices where a large number of surgical procedures are performed, is also prudent.3

References
  1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetes Statistics.  June 2016. Accessed February 28, 2019.
  2. Centers for Disease Control and Prevention (CDC) National Diabetes Statistics Report, 2017. Atlanta, GA: U.S. Department of Health and Human Services 2017. Accessed February 28, 2019.
  3. Kidambi S, Patel SB. Diabetes mellitus: considerations for dentistry. J Am Dent Assoc 2008;139 Suppl:8s-18s.
  4. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diagnosis of diabetes and prediabetes.  November 2016. Accessed February 28, 2019.
  5. Centers for Disease Control and Prevention. Mortality in the United States, 2017. 2018. Accessed February 28, 2019.
  6. Centers for Disease Control and Prevention. The Surprising Truth About Prediabetes. Centers for Disease Control and Prevention 2018. Accessed February 28, 2019.
  7. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Low Blood Glucose (Hypoglycemia). National Institutes of Health August 2016. Accessed February 28, 2019.
  8. American Diabetes Association. Hypoglycemia (Low Blood Glucose). August 29, 2018. Accessed February 28, 2019.
  9. Eli Lilly Corp. Glucagon for Injection: Information for the User.  April 2018. Accessed February 28, 2019.
  10. Ship JA. Diabetes and oral health: an overview. J Am Dent Assoc 2003;134 Spec No:4S-10S.
  11. American Diabetes Association. Hyperglycemia (High Blood Glucose). August 30, 2018. Accessed February 28, 2019.
  12. American Diabetes Association. Diabetes Meal Plans and a Healthy Diet. June 1, 2015. Accessed February 28, 2019.
  13. American Diabetes Association. Going low:  hypoglycemia. Diabetes Forecast. May 2015. Accessed February 28, 2019.
  14. U.S. Food & Drug Administration. Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use:  Guidance for Industry and Food and Drug Administration Staff Document no. 1755.: October 11, 2016. Accessed February 28, 2019.
  15. Centers for Disease Control and Prevention/National Center for Health. Statistics About the National Health and Nutrition Examination Survey.  September 15, 2017. Accessed February 28, 2019.
  16. Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. J Am Dent Assoc 2008;139 Suppl:19S-24S.
  17. Mealey BL. Periodontal disease and diabetes. A two-way street. J Am Dent Assoc 2006;137 Suppl:26S-31S.
  18. Ziukaite L, Slot DE, Van der Weijden FA. Prevalence of Diabetes Mellitus in People Clinically Diagnosed with Periodontitis: A Systematic Review and Meta-analysis of Epidemiologic Studies. J Clin Periodontol 2017.
  19. Graziani F, Gennai S, Solini A, Petrini M. A systematic review and meta-analysis of epidemiologic observational evidence on the effect of periodontitis on diabetes An update of the EFP-AAP review. J Clin Periodontol 2018;45(2):167-87.
  20. Kane SF. The effects of oral health on systemic health. Gen Dent 2017;65(6):30-34.
  21. Chapple IL, Genco R, working group 2 of the Joint EFP/AAP Workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol 2013;84(4 Suppl):S106-12.
  22. Sanz M, Ceriello A, Buysschaert M, et al. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol 2018;45(2):138-49.
  23. Ganesan SM, Joshi V, Fellows M, et al. A tale of two risks: smoking, diabetes and the subgingival microbiome. ISME J 2017;11(9):2075-89.
  24. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366(9499):1809-20.
  25. Joaquim CR, Miranda TS, Marins LM, et al. The combined and individual impact of diabetes and smoking on key subgingival periodontal pathogens in patients with chronic periodontitis. J Periodontal Res 2017.
  26. Javed F, Al-Kheraif AA, Salazar-Lazo K, et al. Periodontal Inflammatory Conditions Among Smokers and Never-Smokers With and Without Type 2 Diabetes Mellitus. J Periodontol 2015;86(7):839-46.
  27. Simpson TC, Weldon JC, Worthington HV, et al. Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev 2015(11):CD004714.
  28. Madianos PN, Koromantzos PA. An update of the evidence on the potential impact of periodontal therapy on diabetes outcomes. J Clin Periodontol 2018;45(2):188-95.
  29. Mauri-Obradors E, Merlos A, Estrugo-Devesa A, et al. Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: A randomized controlled trial. J Clin Periodontol 2018;45(3):345-53.
  30. Engebretson SP, Hyman LG, Michalowicz BS, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. JAMA 2013;310(23):2523-32.
  31. Vergnes JN, Canceill T, Vinel A, et al. The effects of periodontal treatment on diabetic patients: The DIAPERIO randomized controlled trial. J Clin Periodontol 2018;45(10):1150-63.
  32. Taboza ZA, Costa KL, Silveira VR, et al. Periodontitis, edentulism and glycemic control in patients with type 2 diabetes: a cross-sectional study. BMJ Open Diabetes Res Care 2018;6(1):e000453.
  33. Rees TD. Endocrine and metabolic disorders. In: Patton LL, Glick M, editors. The ADA Practical Guide to Patients with Medical Conditions. 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2016. p. 71-99.
  34. Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. J Am Dent Assoc 2008;139 Suppl:19s-24s.
  35. Lalla RV, D'Ambrosio JA. Dental management considerations for the patient with diabetes mellitus. J Am Dent Assoc 2001;132(10):1425-32.
  36. Javed F, Romanos GE. Impact of diabetes mellitus and glycemic control on the osseointegration of dental implants: a systematic literature review. J Periodontol 2009;80(11):1719-30.

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Last Updated: April 12, 2019

Prepared by:

Department of Scientific Information, Evidence Synthesis & Translation Research, ADA Science & Research Institute, LLC.


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