Objectives. Good Resource for All. Adult Clinical Update: 2015 Evidence Based Practice Guidelines. Various Organizations Provide Screening Guidelines

Transcription

1 Adult Clinical Update: 2015 Evidence Based Practice Guidelines Wendy L. Wright, MS, RN, APRN, FNP, FAANP, FAAN Adult / Family Nurse Practitioner Owner Wright & Associates Family Healthcare, Amherst Concord Owner Partners in Healthcare Education, LLC This program was developed by Wendy L. Wright APRN and accredited by Partners in Healthcare Education, an approved provider of nurse practitioner continuing education by the American Association of Nurse Practitioners; provider number This program is sponsored through a restricted educational grant from Walgreens 1 Objectives Upon completion of this session, the participant will be able to: Discuss latest evidence based screening guidelines for the adult patient Identify common conditions encountered by the adult patient Discuss treatment options, both pharmacologic and nonpharmacologic, for the adult patient 2 Various Organizations Provide Screening Guidelines In the case of breast cancer guidelines ACS and USPSTF Many organizations endorse or refute established guidelines American College of Radiology (ACR) and American College of Obstetricians and Gynecologists (ACOG) argued against the USPSTF guidelines Various organizations often differ in opinions on screening recommendations providing further confusion Very difficult to be able to keep up with all revisions and recommendations Particularly those in primary care and generalist roles Good Resource for All Become a member of their list serve Receive weekly guideline updates 3 4 1

2 Medicare Check List for Patients Adult Screening accessed Thyroid Serum TSH measurement in adults every 5 years has been shown by decision analysis to have equivalent or favorable cost-effectiveness All adults have their serum TSH concentration measured beginning at age 35 years 5 years thereafter, the interval at which a periodic health examination has been advocated by the US Preventive Services Task Force. More frequent screening may be appropriate in individuals at higher risk of developing thyroid dysfunction. TSH TSH gold standard Normal: ml/ul Hypothyroidism: Increased Hyperthyroidism: Decreased Remains gold standard for screening for all forms of hyperthyroidism and hypothyroidism ysfunc_2000.pdf accessed

3 What About? Elevated TSH and Normal FT4 Subclinical hypothyroidism TSH level is usually < 20 mu/l 5 18% of individuals with this progress to overt hypothyroidism yearly Progression is more likely if anti-thyroid antibodies are present If antibodies are present, the patient has symptoms of hypothyroidism, and TSH is elevated ( > 5.0) may treat Lung Cancer Screen: People who are current smokers (or have quit within the last 15 years) and are aged 55 to 79 years old who have a smoking history of 30 pack-years or greater Low Dose CT scan annually as long as patient remains healthy accessed USPSTF Aortic Aneurysm Medicare One-time screening for abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65 to 75 who have ever smoked. No recommendation for or against screening for AAA in men aged 65 to 75 who have never smoked. Recommends against routine screening for AAA in women. Ultrasound to screen for AAA is covered if the recipient has at least one of the following risk factors a family history of abdominal aortic aneurysm is a man age 65 to 75 who has smoked at least 100 cigarettes in his lifetime accessed accessed

4 Osteoporosis Guidelines vary significantly with regard to assessment of risk factors all adult patients age 50 (American College of Preventive Medicine all postmenopausal women (The North American Menopause Society) ening accessed BMD Testing BMD testing for all postmenopausal women aged 65 years or older, regardless of clinical risk factors (NAMS and ACPM) BMD testing should be recommended for postmenopausal women younger than 65 (NAMS specifies women 50) when risk factors (identified during the risk assessment) are present ening accessed NOF Recommendations BMD: in women age 65 and older and men age 70 and older BMD: in postmenopausal women and men age 50-69, when concern is present based on their risk factor profile BMD testing to those who have had a fracture, to determine degree of disease severity Revised: February 2008 Clinician s Guide to the Prevention and Treatment of Osteoporosis accessed accessed

5 FRAX Summary of Revisions WHO Fracture Risk Assessment Model/Tool Provides 10 year probability of fracture risk New risk assessment tool Summary of Revisions Treatment Recommendations Treat all individuals with a T score of -2.5 in the hip Those with T scores of 1.5 to -2.5 (osteopenia) should be treated when the 10 year probability of a hip fracture is >3% (FRAX model) ORthe 10 year probability of a major osteoporosis related fracture is >20% based upon the US adapted WHO criteria (FRAX model) accessed accessed FRAX (online tool) WHO Fracture Risk Assessment Tool FRAX (online tool) 19 assessed at

6 Fracture per 1000 Person-Years Population BMD Distribution, Fracture Rates, and Number of Women With Fractures BMD distribution Fracture rate No. of women with fractures > to to to to 3.0 < to to to to to 3.5 BMD T-Scores (Peripheral) Adapted from Siris ES, et al. Arch Intern Med. 2004;164: No. of Women With Fractures Summary: Important To Remember One-half or more of our fractures occur in individuals with T scores better than -2.5 SD. Thus, treating by BMD alone may not be the answer. Hence, the new revisions to the guidelines. Waxman, J. Making the best use of osteoporosis agents. Clinical Advisor, December Accessed on 1/13/2008 Siris, E. Archives of Internal Medicine : ACS - Breast Cancer BSE Option for women beginning: 20 years of age CBE Every 3 years for women: years of age Yearly: 40 years of age and older Yearly mammograms Beginning at age of 40 Continue as long as the woman is in good health accessed USPSTF Breast Cancer Guidelines Women years: Biennial screening The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient s values regarding specific benefits and harms. Current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older Recommends against teaching breast self-examination (BSE). Current evidence is insufficient to assess the additional benefits and harms of clinical breast examination (CBE) beyond screening mammography in women 40 years or older. Current evidence is insufficient to assess the additional benefits and harms of either digital mammography or magnetic resonance imaging (MRI) instead of film mammography as screening modalities for breast cancer. accessed

7 Fortunately Most insurances are still paying for mammograms according to the ACS guidelines at this time What the future holds, remains to be seen Colorectal Cancer Screening should begin at the age of 50 in both men and women Recommended screening options: Flexible Sigmoidoscopy every 5 years Colonoscopy every 10 years CT colonography (virtual colonoscopy) every 5 years Double-contrast barium enema every 5 years FOBT-three stool cards: option but clearly not preferred Stool based DNA testing accessed ACG Guidelines ACG Guidelines Screening is recommended in African Americans beginning at age 45 years Colonoscopy every 10 years, beginning at age 50 Patients should be offered an alternative CRC prevention test: Flexible sigmoidoscopy every 5 10 years Computed tomography (CT) colonography every 5 years Cancer detection test (fecal immunochemical test for blood) accessed Single 1st-degree relative with CRC or advanced adenoma diagnosed at age < 60 years or two 1st-degree relatives with CRC or advanced adenomas Colonoscopy every 5 years beginning at age 40, or 10 years younger than age at diagnosis of the youngest relative accessed

8 Medicare Coverage Fecal Occult Blood Test Once every 12 months if 50 or older Flexible Sigmoidoscopy: Generally, once every 48 months Or 120 months after a previous screening colonoscopy for people not at high risk. Screening Colonoscopy: Generally once every 120 months (once every 24 months if high risk), or 48 months after a previous flexible sigmoidoscopy Barium Enema: Every 48 months if 50 or older; every 24 months if high risk accessed Cervical Cancer Begin screening: Age 21, regardless of age of onset of intercourse Frequency: dependent upon age Age 21-29: every 3 years; only use HPV testing in this group if ASCUS pap Age years: Pap + HPV testing every 5 years but okay to have pap alone every 3 years > 65 years with regular pap screenings: may stop; must be 20 years after precancerous pap accessed Cervical Cancer Hysterectomy (uterus and cervix) May choose to stop having pap tests unless surgery was for cancer or precancer If cervix is still present, should continue paps according to above instructions Women vaccinated with HPV immunization Follow same schedule as discussed on previous slide and above accessed ACOG Guidelines Cervical cancer screening should begin at age 21 years Ages: Every 3 years 30 years 65 years Every 5 years with HPV co-testing Every 3 years independently > 65 years Negative prior screenings and no CIN2 or above in past 20 years may stop ng_recommendations accessed

9 ACOG Guidelines Women who have had a total hysterectomy for benign indications and have no prior history of high grade CIN Discontinue routine cytology testing American Society for Colposcopy and Cervical Pathology 2009 Addendum Women with ASC-US who are HPV DNA negative can be followed up with repeat cytologic testing at 12 months ASC-US who are HPV DNA positive should be managed in the same fashion as women with LSIL and be referred for colposcopic evaluation ng_recommendations accessed consensus guidelines for the management of women with abnormal cervical cancer screening tests addendum. Hagerstown (MD): American Society for Colposcopy and Cervical Pathology; p. [5 references] 34 Update 2013 Importance Still in need of STI screening May screen for chlamydia and GC using urine testing Do not reinitiate pap smear screening, once stopped, even in women with new sexual partner

10 Numerous Prostate Cancer Guidelines American College of Preventive Medicine (ACPM). Screening for prostate cancer in U.S. men. Am J Prev Med 2008 Feb;34(2): American Urological Association (AUA). Prostatespecific antigen best practice statement: 2009 update. Linthicum (MD): American Urological Association Education and Research, Inc.; U.S. Preventive Services Task Force (USPSTF). Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008 Aug 5;149(3): All Organizations. Recognize controversy re: PSA screening and lack of evidence re: reduced mortality Also recognize that routine screening may increase treatment morbidity Agreement from the three organizations: Insufficient evidence to recommend routine screening for prostate cancer in any age group Decision to undergo screening should be an individualized, informed decision on the part of the patient in consultation with his healthcare provider Clinicians should inform men of the potential benefits, known risks (including overdetection and overtreatment), as well as the limits/gaps in current evidence Discussion about screening should occur annually, during the routine periodic examination, or in response to a request by the patient ening accessed Prostate Cancer Beginning at age of 50: Begin to speak with patient re: pros and cons of PSA testing African Americans or a first degree relative with prostate cancer before age 65 Begin screening at age 45 years STAY TUNED!!! Hepatitis C Screening All individuals born between 1945 and 1965 should be screened for hepatitis C Estimated that there are 4 million individuals with Hepatitis C in this age group who are unaware accessed accessed

11 Hypertension Blood pressure screening for children should start at age 3 American Academy of Pediatrics, the American Heart Association, and the American Medical Association (AMA) Recommend that children aged 3 years and older who are seen in medical care settings should have their blood pressure measured at least once during every healthcare episode The U.S. Preventive Services Task Force recommends that all adults aged 18 years and older for be screened for hypertension accessed Diagnosis 2 readings in the absence of TOD establishes diagnosis 1 reading in the presence of TOD Ideally, separated apart by several weeks The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, And Treatment of High Blood Pressure. Assessed Recommendations for Follow-up Normal: Recheck every 2 years Prehypertension: Recheck in 1 year Stage 1 Hypertension: Confirm within 2 months Stage 2 Hypertension: Evaluate within 1 month For those with higher pressures (e.g., >180/110 mmhg), evaluate and treat immediately or within 1 week depending on clinical situation and complications accessed Hyperlipidemia ATP III Fasting lipid profile Beginning at age of 20 years of age If normal, repeat every 5 years If patient is likely to not return for a fasting lipid profile Obtain non-fasting HDL and non-fasting total cholesterol accessed

12 USPSTF Recommendations Men Screen all men 20 years of age and older if they are at increased risk for coronary heart disease Women Screen all women aged 20 years and older if they are at increased risk for coronary heart disease. Young Men and All Women Not at Increased Risk The USPSTF makes no recommendation for or against routine screening for lipid disorders in men aged 20 to 35, or in women aged 20 and older who are not at increased risk for coronary heart disease. U.S. Preventive Services Task Force. Screening for lipid disorders in adults: U.S. Preventive Services Task Force recommendation statement. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2008 Jun. 13. accessed Screening Adults for Obesity Clinicians should screen all adult patients for obesity and offer intensive counseling and behavioral interventions to promote sustained weight loss for obese adults Body mass index (BMI) is reliable and valid for identifying adults at increased risk for mortality and morbidity due to overweight and obesity. Fair to good evidence exists that high-intensity counseling about diet, exercise, or both together with behavioral interventions aimed at skill development, motivation, and support strategies produces modest, sustained weight loss (typically 3-5 kg for 1 year or more) in adults who are obese (as defined by BMI 30 kg/m 2 ). accessed BMI >30 obesity >25 overweight ADA is recommending that screening for diabetes be done on Asian-Americans at 23 kg/m2 or higher. Asian Americans develop diabetes at lower BMI levels because of differences in their body composition: weight gain tends to accumulate around the waist in Asian Americans, the area in which adiposity is considered most harmful from a disease standpoint, rather than in the thighs and other parts of the body accessed Immunizations 48 12

13 Adult Immunization Schedule 2015 New: August 2014 All 65 years of age and older: Offer PCV13 first at age 65 or as soon as able 6 12 months later, follow with PPV23 Medicare is NOW covering both of these so..give PCV13 and 1 year later, follow with PPV23 If already had PPV23, as long as one year has elapsed, give PCV13, then.as long as 5 years has elapsed, give PPV23 and done! accessed Pneumococcal Recommendations Pneumococcal Recommendations Pneumococcal Naïve & >65 years Previously vaccinated with PPSV23 at age > 65 years PCV13: First PPSV23: 6-12 months later PCV13 (as least 1 year after most recent dose of PPSV23) Adults previously vaccinated with PPSV23 before age 65 years who are now aged >65 years PCV13: First (as least one year after the most recent dose of PPSV23) 6-12 months later: PPSV23 (no sooner than 5 years after the most recent dose of PPSV23) 13

14 Herpes Zoster Vaccine One time only for individuals 60 and older Administer even if they have a history of herpes zoster Do not need to confirm varicella antibodies SC injection Approximately $ for injection No quarantine necessary unless individual develops rash at site of injection accessed Herpes Zoster Vaccine Herpes zoster vaccination should not be given to: Pregnant women Persons with a primary or acquired immunodeficiency Persons with a history of anaphylactic reaction to gelatin, neomycin, or any other component of the vaccine Herpes zoster vaccine can be administered simultaneously with other indicated vaccines accessed Initial Warning May co-administer with influenza vaccine Co-administration of Zoster vaccine (Zostavax) and PPV23 during the same visit may result in decreased immunogenicity from Zoster vaccine (Zostavax) Update Giving PPV 23 and Herpes Zoster vaccine together was no more likely to lead to herpes zoster than giving them between 30 days or a year apart Study conducted by Hung Fu Tseng and colleagues at Southern California Kaiser Permanente in Pasadena CDC recommends giving two vaccinations together if patient is eligible accessed

15 Herpes Zoster Vaccine Update Immunization and the injection fee will need to be billed under Medicare Part D What does this mean for us: Collect money from patients first; give them charges and they have to submit Or.Medicare has a new electronic billing system called Transact RX Lets offices bill many Part D plans for immunization and the injection fee Will also verify coverage, calculate co-pay and bill insurance company for remainder Herpes Zoster Vaccine New information: May remain in refrigerator for up to 72 hours once removed from freezer Is now approved by FDA and indicated to be given at 50 years of age New March 2015 Complete reconfiguration of flu vaccine for H3N2 (new Switzerland strain) H1N1 A/California/7/2009 B strain, B/Phuket/3073/2013 virus strain B strain, Brisbane/60/2008 High Dose Influenza Vaccine The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) decided to: Include High-Dose influenza vaccine (Fluzone High-Dose, Influenza Virus Vaccine) among the vaccines recommended for adults 65 years of age and older in its annual influenza prevention recommendations 59 15

16 Efficacy Study on High Dose vs. Standard Dose Influenza Vaccine High dose vs. standard dose in individuals >65 years of age 24.2% more effective in preventing flu and complications than standard dose flu vaccine Studied more than 30,000 individuals accessed Recent Study on High Dose Influenza Vaccine Studied: 190 HIV patients Vaccine indicated at present for individuals 65 years of age and older Those receiving high dose influenza vaccine had more seroprotection against the flu than those who received normal doses For every antigen studied, the high-dose formulation increased average antibody titers and resulted in higher seroconversion and seroprotective rates when compared with the standard-dose influenza vaccine accessed Egg Allergy and TIV The recommendation is as follows: For patients with a history of egg allergy WITHOUT anaphylaxis, there is no need to divide doses or perform skin testing before vaccination There will be no need to confirm the levels of ovalbumin in the flu vaccine because all products will contain less than 0.6 micrograms per dose; Patients with egg allergy should be observed for 30 minutes after vaccination; and vaccine providers should be equipped and trained to handle anaphylactic emergencies Do not use LAIV (Flumist) Hepatitis B 16

17 Hepatitis B Vaccination Hepatitis B vaccination should be administered to: Unvaccinated adults with diabetes mellitus who are aged 19 through 59 years Hepatitis B vaccination may be administered at the discretion of the treating clinician to unvaccinated adults with diabetes mellitus who are aged 60 years Administration of the hepatitis B vaccine series should be completed as soon as feasible after diabetes is diagnosed 050a4_w accessed Hepatitis B Vaccination Reasons for vaccination: Risk posed by an increased need for assisted bloodglucose monitoring in LTC facilities, the likelihood of experiencing chronic sequelae if infected with HBV, and the declining immunologic responses to vaccines that are associated with frailty, a geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability, leading to early mortality in older adults 050a4_w accessed New 2013 Tdap with each pregnancy Regardless of interval and previous vaccination with Tdap Tdap Issue Remaining What to do with individuals who have received Tdap and are in need of another Td vs. Tdap Tdap revaccination (June 2013) Meeting agenda for June 2013 Did not vote for revaccination of population, other than pregnant women 17

18 Recently approved HPV 9 5 additional strains of protection Will provide an additional 20% reduction in cervical cancer Approved: Same approvals as HPV years of age girls and boys Now available EENT Disorders 70 Visual Screening Eyes (For information on viral, bacterial, and allergic conjunctivitis, please consult Pediatric Guidelines) Should be performed on all adult and pediatric well-child visits Should be performed on all ocular complaints Snellen and retinal examination Considered to be the vital sign of the eye

19 Case Study 1: M.R. 46 y.o.w.m presents with a 3 hour history of a headache, located behind his right eye Never had anything like this before 9 on a 1-10 scale (10 severe pain) Associated with blurred vision and watering in right eye Denies trauma, history of systemic or ocular diseases Meds: none Allergies: NKDA Case Study 1: M.R. PE: Slightly dilated pupil (OD), Nonreactive and mild injection. Firm globe. IOP: 80. Remainder of physical examination-normal Acute Angle Closure Glaucoma Acute Angle Closure Glaucoma Signs Injected eye Mid-dilated nonreactive pupil Steamy, cloudy cornea Firm globe Increased intraocular pressure (40-80) Narrow angle Shallow anterior chamber in other eye May simulate a cerebral bleed accessed

20 Narrow Angles Acute Angle-Closure Glaucoma accessed accessed Acute Angle Closure Glaucoma Herpes Simplex Treatment Ocular emergency Immediate referral for treatment Medical Management Hyperosmotic agents Diamox and eye drops Surgical Treatment accessed

21 Blowout Fracture Orbital cellulitis Immediate ENT or ED referral Antibiotics IV will be administered Stat CT and labs Ears (For AOM, OME and OE, please consult Pediatric Guidelines) Nose and Sinuses (For allergic rhinitis, please consult Pediatric Guidelines)

22 Causative Pathogens in ABRS Pathogens and Resistance Streptococcus pneumoniae Major pathogens in sinusitis Haemophilus influenzae Moraxella catarrhalis Prevalence of Respiratory Pathogens Streptococcus pneumoniae Gram positive diplococci Most common cause of Community Acquired Pneumonia Also the most common bacterial cause of OM and sinusitis 70% of children and 30% of adults have nasopharyngeal colonization Disease results from a microaspiration accessed

23 Mechanism for the Development of Antimicrobial Resistance Streptococcus Pneumoniae Resistance Streptococcus pneumoniae Many mechanisms for resistance Most common mechanism: Resistance from an alteration in the penicillin binding proteins which reduce/eliminate binding of penicillin to the proteins Mechanism for the Development of Antimicrobial Resistance Streptococcus pneumoniae Erythromycin resistance: ribosome modification and alteration in antibiotic transport Of increasing concern is the ermam gene. This gene confers cross-resistance to other 14, 15, and 16 membered rings (clarith, azith) Where are we now? S. pneumoniae 25% - 50% is not fully responsive to penicillin 33% is resistant to macrolides

24 Of Increasing Concern Streptococcus pneumoniae The first clinical isolate of S. pneumoniae to exhibit a high level of resistance to fluoroquinolones was found in 2001 in Taiwan Most likely to be present with recurrent disease and least likely of all pathogens to resolve without treatment <30% chance of spontaneous resolution; Some sources say <10% H. influenzae M. catarrhalis Gram negative coccobacillus Bronchotracheal tree becomes colonized and microaspiration occurs Most commonly seen among smokers, children of smokers and daycare children 33% - 35% of H. influenzae is beta lactamase producing TRUST results (Tracking Resistance in the United States) 31.3% produced B lactamase in TMP-SMX resistance increased to 14% from 11.9% Ampicillin resistance decreased from 33.9% to 30.7% Gram negative bacillus Implicated in recurrent OM and Sinusitis Will often spontaneously resolve if left untreated 90% - 98% beta lactamase producing

25 Tammy Acute Bacterial Rhinosinusitis year old woman with an 12 day history of nasal discharge Seemed to be improving until past 2 days; developed worsening of post-nasal drip and pain over both cheeks. Temp past 1-2 days: Last antimicrobial use: 1 year ago PMH: Noncontributory; No tobacco, No allergies LMP: 2 weeks ago; denies pregnancy PE: Nasal mucosa erythematous. Maxillary sinuses 2+ tender 98 Remember Predisposing Factors of ABRS Secondary bacterial infection of the paranasal sinuses following a viral URI is relatively uncommon, estimated to be 0.5% 2% of adult cases and approximately 5% in children A national survey of antibiotic prescriptions for URI in the outpatient setting showed that antibiotics were prescribed for 81% of adults with acute rhinosinusitis despite the fact that approximately 70% of patients improve spontaneously in placebocontrolled randomized clinical trials 99 accessed Upper respiratory infections Colds Immunodeficiency syndromes Anatomical abnormalities Allergy Smoking Dental infections

26 Diagnosis of Bacterial Acute Sinusitis Who should be treated with antimicrobial: Persistent symptoms or signs compatible with acute rhinosinusitis, lasting for 10 days without any evidence of clinical improvement Onset with severe symptoms or signs of high fever ( 39 C [102 F]) and purulent nasal discharge or facial pain lasting for at least 3 4 consecutive days at the beginning of illness Onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5 6 days and were initially improving ("double sickening") accessed Diagnostic Testing Sinus X-rays Allows visualization of the maxillary and frontal sinuses Lack of specificity is a limiting factor US Agency on Healthcare Policy not cost effective CT Scan Best visualization of the paranasal sinuses Not recommended unless patient suspected to have suppurative complications 2 accessed accessed Normal sinuses Sinus Disease Source: MD Consult Online. Available at Accessed Source: American Academy of Allergy Asthma and Immunology. Available at Accessed

27 Cultures: What and When to Recommend Cultures should be obtained by direct sinus aspiration rather than by nasopharyngeal swab in patients with suspected sinus infection who have failed to respond to empiric antimicrobial therapy Endoscopically guided cultures of the middle meatus may be considered as an alternative in adults, but their reliability in children has not been established Nasopharyngeal cultures are unreliable and are not recommended for the microbiologic diagnosis of ABRS accessed IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults Clinical Infectious Diseases Advance Access published March 20, Accessed Goals of Treatment Restore integrity and function of osteomeatal complex Reduce inflammation Restore drainage Eradicate bacterial infection Treatment of Acute Bacterial Rhinosinusitis Nonpharmacologic Therapies Cold steam vaporizer Increased water intake Intranasal saline irrigations with either physiologic or hypertonic saline are recommended as an adjunctive treatment in adults with ABRS 1 accessed Accessed

28 Management Strategies in ABRS Antihistamines or decongestants No longer recommended Topical corticosteroids Intranasal corticosteroids are recommended as an adjunct to antibiotics in the empiric treatment of ABRS, primarily in patients with a history of allergic rhinitis 1 Corticosteroids 1 Accessed Initial Antimicrobial Regimen for Adults with ABRS First line therapy Amoxicillin-clavulanate rather than amoxicillin alone is recommended as empiric antimicrobial therapy for ABRS in adults and children Standard dosage: 500 mg/125 mg 1 pill po three times daily or. 875mg/125mg 1 pill two times daily Initial Antimicrobial Regimen for Adults with ABRS (Risk for resistance) Second line therapy Amoxicillin-clavulanate 2000mg/125 mg 1 pill two times daily or. Doxycycline 100 mg 1 pill two times daily or 200 mg once daily Accessed Accessed

29 Initial Antimicrobial Regimen for Adults with ABRS Individuals with B-lactam allergy Doxycycline 100 mg 1 pill two times daily or 200 mg once daily or Levofloxacin 500 mg 1 pill once daily or. Moxifloxacin 400 mg 1 pill once daily Accessed Antimicrobial Regimen for ABRS in Adults at Risk for Resistance or Failed Initial Therapy Amoxicillin-clavulanate 2000 mg/125mg 1 pill two times daily or Levofloxacin 500 mg 1 pill once daily or. Moxifloxacin 400 mg 1 pill once daily accessed What Constitutes at Risk for Resistance? Age < 2 years or > 65 years Daycare Antimicrobial within past 1 month Hospitalization within past 5 days Comorbidities Immunocompromised Accessed Important Changes Macrolides (clarithromycin and azithromycin) are not recommended due to high rates of resistance among S. pneumoniae (30%) TMP/SMX is not recommended due to high rates of resistance among both S. pneumoniae and H. influenzae (30% 40%) Second and third-generation cephalosporins are no longer recommended due to variable rates of resistance among S. pneumoniae. accessed

30 Summary: Antimicrobial Regimens in Adults Length of treatment The recommended duration of therapy for uncomplicated ABRS in adults is 5 7 days In children with ABRS, the longer treatment duration of days is still recommended Accessed Accessed When to Change Treatments When to Refer An alternative treatment should be considered if symptoms worsen after hours of initial empiric antimicrobial therapy, or when the individual fails to improve despite 3 5 days of antimicrobial therapy Accessed Accessed

31 Mouth (For pharyngitis, please consult the Pediatric Guidelines) Pulmonary/Respiratory Bronchitis 90% of cases are viral American College of Chest Physicians Ipratropium bromide Albuterol Prednisone Cough suppressants If bacterial, mycoplasma must be considered Consider B. pertussis Community Acquired Pneumonia accessed

32 Earl 56 year old man employed by the town presents with a 6 day history of a cough, worsening sob, fever, chills, pain in back with inspiration, and yellow-brown sputum. PMH: Nonsmoker; quit 15 years ago PE: Crackles in right lower lobe; Do not clear with coughing X-ray: Consolidation-RLL Sputum Gram Stain: Pending Community Acquired Pneumonia Acute infection of the pulmonary parenchyma that is associated with symptoms of an infection such as fever, chills, shortness of breath and physical examination findings Found in a person not hospitalized or residing in a long-term care facility for >14 days before the onset of symptoms Statistics: Community Acquired Pneumonia 915,900 episodes of CAP occur in adults 65 years of age each year in the United States Despite advances in antimicrobial therapy, rates of mortality due to pneumonia have not decreased significantly since penicillin became routinely available Community Acquired Pneumonia Leading cause of death from an infectious disease 6th leading cause of death 45,000 deaths in the US yearly Highest incidence: winter months accessed

33 Symptoms of Pneumonia Cough Shortness of breath Fever Pleurisy Sputum production Fatigue Malaise Anorexia Signs Fever Tachypnea Tachycardia Crackles or decreased breath sounds Egophony, Bronchophony, Whispered Pectoriloquy Increased tactile fremitus Pleural rub Most Common Outpatient Pathogens Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses accessed Earl 56 year old man employed by the town presents with a 6 day history of a cough, worsening sob, fever, chills, pain in back with inspiration, and yellow-brown sputum. PMH: Nonsmoker PE: Crackles in right lower lobe; Do not clear with coughing. RR 20; Blood pressure 110/76 X-ray: Consolidation-RLL Sputum Gram Stain: Pending CBC: wbc 16,500; Bands 7%, Neuts: 73%

34 Most Important Decision!!! Decision to hospitalize or not Single most important decision in the course of the illness Can determine life or death Average mortality for hospitalized patients: 14% compared with non-hospitalized: <1% Average cost of treatment for CAP in the hospitalized patient vs. non-hospitalized $7500 (20x more than non-hospitalized) Confusion CURB-65 Score Urea > 7 mmol/l (BUN > 19 mg/dl) Respiratory rate > 30/min Systolic blood pressure < 90 mm and Diastolic blood pressure <60 mm Hg Age >65 years of age accessed CURB-65 Score CURB >4 ICU management (27.8% 30-day mortality) CURB = 3 Hospital admission (consider ICU) (14% 30-day mortality) CURB = 2: Hospital admission or outpatient management with very close follow-up (6.8% 30-day mortality) CURB = 0 1: Outpatient management (2.7% 30-day mortality) Remember Earl... Age: 56 Confusion 0 Urea 0 Respiratory rate 0 Blood pressure 0 Age 0 CURB Score 0 - outpatient accessed

35 Diagnosis All patients suspected of pneumonia need to have a chest x-ray to confirm or establish the diagnosis CBC; with other labs dictated by comorbidities Infectious Disease Society of America also recommends sputum for gram staining prior to initiating antibiotic therapy, particularly if you are going to be hospitalizing the individual accessed Please Remember... Four potential causes of a false negative chest x- ray Early disease: Delay can be up to 10 days Dehydration: Controversial but must be considered Neutropenia: Unable to mount an inflammatory response Pneumocystis Carinii: 10-40% of patients with this infection have a normal x-ray 138 Sputum Sample: To obtain or not? Prospective studies have failed to identify the cause of 40-60% of all CAP cases in the adult patient However, S. pneumoniaeis the most common cause of CAP Responsible for approximately 2/3 of all cases of bacteremic pneumonia IDSA/ATS 2007 Guidelines for CAP in Adults Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults Revised and published in Clinical Infectious Diseases 2007;44:S27 S72 accessed on accessed

36 IDSA/ATS CAP Outpatient Treatment Classification Previously healthy, no recent (within past 3 months) antibiotic use Likely causative pathogens S. pneumoniae (Gm pos) with low DRSP risk Atypical pathogens (M. pneumoniae, C. pneumoniae) Respiratory virus including influenza A/B, RSV, adenovirus, parainfluenza IDSA/ATS CAP Outpatient treatment Strong recommendation Macrolide such as azithromycin, clarithromycin, or erythromycin Or Weak recommendation Doxycycline Classification IDSA/ATS CAP Outpatient treatment Comorbidities including: COPD, diabetes, renal or heart failure, asplenia, alcoholism, immunosuppressing conditions or use of immunosuppressing medications, malignancy or use of an antibiotic in past 3 months IDSA/ATS CAP Outpatient treatment Likely causative organism S. pneumoniae(gm pos) with DRSP risk H. influenzae(gm neg) Atypical pathogens (M. pneumoniae, C. pneumoniae, Legionella) Respiratory virus as mentioned above

37 IDSA/ATS CAP classification for outpatient treatment Respiratory fluoroquinolone Or Advanced macrolide (azithromycin or clarithromycin) plus b-lactam such as HD amoxicillin (3-4 g/d), high dose amoxicillinclavulanate (4 g/d), ceftriaxone (Rocephin), cefpodoxime (Vantin), cefuroxime (Ceftin) Alternative to macrolide: doxycycline 145 Criteria Antibiotic Options Antibiotic Options Antibiotic Options IDSA / ATS 2007 Guidelines Previously Healthy and No Risks for DRSP Strong: Macrolide Weaker: Doxycycline Previously Healthy and Recent Antibiotics Respiratory Quinolone Macrolide + High dose amoxicillin Macrolide + High Dose amox/clav Comorbidities and No Recent Antibiotics Respiratory Quinolone Macrolide + Beta Lactam Comorbidities and Recent Antibiotics Respiratory Fluoroquinolone Advanced Macrolide plus beta lactam ***> 25% of infection with high level Macrolide resistance - Quinolone 146 Continuing With Earl 56 year old man employed by the town presents with a 6 day history of a cough, worsening sob, fever, chills, pain in back with inspiration, and yellow-brown sputum. PMH: Nonsmoker PE: Crackles in right lower lobe; Do not clear with coughing. RR -20 X-ray: Consolidation-RLL Sputum Gram Stain: Pending CBC: wbc 16, 5000; Bands 7%, Neuts: 73% Macrolide x 5 days Treated With... Clinical improvement within 48 hours Chest x-ray: who should be repeated? Newer guidelines don t address this issue Older guidelines say 6 12 weeks after treatment Guidelines in other countries: Increased risk of cancer: > 50 years of age and/or smoker accessed

38 Length of Therapy Shortened to 5 days Provided that the patient is afebrile by hours Asthma Prevalence of Asthma Impacts approximately 21 million individuals in the United States Most common chronic disease of childhood affecting 6 million children Before adolescence, 2 times more common in boys Increasing incidence of this disease 76% increase in the prevalence of asthma within the past decade Impact of Asthma Most frequent cause for hospitalization in children (470,000 each year) Emergency room visits and hospitalizations are increasing Most frequent cause of childhood death, particularly amongst certain groups (children, African Americans) ,000 people die yearly from asthma Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics NIH, NHLBI. June NIH publication no Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma-united States, MMWR Surveill Summ. 2002;51:

39 Components of Asthma Asthma Triggers Allergens Exercise Irritants Viruses Weather Consequences of Inflammation in Asthma Stimulus (Antigen, virus, pollutant, occupational agent) Smooth Muscle Dysfunction Hypertrophy Hyperplasia Inflammatory Mediator Release Bronchial Constriction Architectural Changes Bronchial Hyperreactivity Inflammation Mucus Secretion Epithelial Damage Edema Impaired Ciliary Function Inflammatory Cell Infiltration Altered airway physiology Airflow obstruction Airway dysfunction Acute Inflammation Chronic Inflammation Injury Repair Resolution Symptoms Exacerbations 153 Adapted from Creticos. Adv Stud Med. 2002;2(14): Permanently altered lung function Remodeling (fixed changes in the structure of airway) 154 Asthma is... A disease of: Inflammation Primary Process Hyperresponsiveness Airway bronchoconstriction Excessive mucous production Diagnosis of Asthma

40 Diagnosis of Asthma History and Physical Examination Spirometry is needed to make diagnosis Monitoring: Peak Flow Meters Table 10-14: Classification of Asthma Severity (Youths 12 Years of Age and Adults) Initial Diagnosis: Determine Severity and Treatment Needed Components of Severity Impairment Normal FEV 1/FVC: 8-19 yr 85% yr 80% yr 75% yr 70% Risk Symptoms Nighttime awakenings Short-acting beta 2- agonist use for symptom control (not prevention of EIB) Interference with normal activity Lung function Exacerbations requiring oral systemic corticosteroids Persistent Intermittent Mild Moderate Severe 2 days/week 2x/month 2 days/week >2 days/week but not daily 3-4x/month >2 days/week but not >1x/day Daily >1x/week but not nightly Throughout the day Often 7x/week Daily Several times per day None Minor limitation Some limitation Extremely limited Normal FEV 1 between exacerbations FEV 1 >80% predicted FEV 1/FVC normal 0-1/year (see note) FEV 1 >80% predicted FEV 1/FVC normal 2/year (see note) FEV 1 >60% but <80% predicted FEV 1/FVC reduced 5% FEV 1 <60% predicted FEV 1/FVC reduced >5% Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV Asthma Findings Asthma Typically, reversibility of 12% or greater after administration of a bronchodilator aerosol is consistent with asthma. Hyperinflation Diaphragm is down to the 11 th ribs Most patients with asthma have normal x-rays Conboy-Ellis, Kathleen. Asthma: Pathogenesis and Management. The Nurse Practitioner: November 2006; Vol.31, No

41 Chronic Asthma Changes Increased AP Lateral diameter The way you know that AP/Lat diameter is increased is by this clear space between the sternum and the ascending aorta Flat diaphragms Treatment of Asthma Evolution of Asthma Paradigms Symptoms Bronchial Hyperreactivity Fixed Obstruction Childhood Asthma Control Can Predict Adult Lung Status Study of 119 asthmatic children during 1966 and 1969 Ages: 5-14 were evaluated using FEV1 Follow-up performed years later and years later Children who were well controlled during childhood had the smallest decline in total lung volume during adulthood Relieve Symptoms Prevent Symptoms Prevent Attacks Prevent Symptoms Prevent Attacks Prevent Remodeling

42 Rate of Decline in FEV 1 Changes With Age in FEV 1 According to Smoking and Asthma Status Male Smokers No asthma (n=9332) Asthma (n=630) Male Nonsmokers No asthma (n=5480) Asthma (n=314) FEV 1 /Ht 3 (L/m 3 ) Normal subjects (n=186) 1.3 Height- Adjusted 1.1 FEV 1 (liters) Height- Adjusted 1.1 FEV 1 (liters) Asthma patients (n=66) Age (yr) Age (Yrs.) Adapted from Peat. Eur J Respir Dis. 1987;70: Lange Wright, et 2015 al. N Engl J Med. 1998;339: Age (yr) Table 10-14: Classification of Asthma Severity (Youths 12 Years of Age and Adults) Initial Diagnosis: Determine Severity and Treatment Needed Impairment Components of Severity Normal FEV 1/FVC: 8-19 y 85% y 80% y 75% y 70% Symptoms Persistent Intermittent Mild Moderate Severe 2 days/week >2 days/week but not daily Nighttime awakenings 2x/month 3-4x/month Short-acting beta 2-agonist use for symptom control (not prevention of EIB) Interference with normal activity Lung function 2 days/week >2 days/week but not >1x/day Daily >1x/week but not nightly Daily Throughout the day Often 7x/week Several times per day None Minor limitation Some limitation Extreme limitation Normal FEV 1 between exacerbations FEV 1 >80% predicted FEV 1 >80% predicted FEV 1 >60% but <80% predicted FEV 1 <60% predicted FEV FEV 1/FVC normal FEV 1/FVC normal 1/FVC reduced FEV 1/FVC reduced 5% >5% 0-1/year (see note) 2/year (see note) Exacerbations requiring Consider severity and interval since last exacerbation. Frequency and severity may Risk oral systemic fluctuate over time for patients in any severity category. corticosteroids Relative annual risk of exacerbations may be related to FEV 1 Step 3 Step 4 Step 1 Step 2 and consider short course of oral Recommended Step for initiating Treatment systemic corticosteroids In 2 to 6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly. 167 Intermittent Asthma Stepwise Approach for Managing Asthma in Patients Aged 12 Years Persistent Asthma: Daily Medication Consult with asthma specialist if Step 4 care or higher is required. Consider consultation at Step 3. Step 5 Step 6 Step 4 Preferred: Step 3 Preferred: Preferred: High-dose ICS Preferred: Step 2 Medium-dose High-dose ICS + + LABA + Oral Low-dose ICS + Step 1 Preferred: ICS + LABA (B) LABA (B) Corticosteroid LABA (A) Low-dose ICS Alternative: AND AND (A) OR Medium-dose Preferred: Alternative: Consider Consider Medium-dose ICS + SABA PRN Cromolyn (A), ICS (A) Omalizumab Omalizumab either LTRA (A), Alternative: for Patients for Patients Nedocromil (A), Low-dose ICS + LTRA (B), Who Have Who or either LTRA (A), Theophylline (B), Allergies (B) Theophylline (B), or Zileuton (D) Have Theophylline (B) or Zileuton (D) Allergies Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma Quick-relief medication for all patients SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment168 Step Up if Needed (first, check adherence, environmental control, and comorbid conditions) Assess Control Step Down if Possible (and asthma is well controlled at least 3 months) 42

43 Major Focus in EPR-3 Controlling asthma is a major focus of the EPR-3 guidelines 169 Assessing Asthma Control (Youths 12 Years of Age and Adults) Follow-up Visits: Determine Level of Control and Treatment Needed Components of Control Impairment Symptoms Well-controlled Not Wellcontrolled Very Poorly Controlled 2 days/week >2 days/week Throughout the day Nighttime awakenings 2 x/month 1-3x/week 4x/week Interference with normal activity Short-acting beta 2- agonist use for symptom control (not prevention of EIB) FEV 1 or peak flow Validated Questionnaires ATAQ ACQ ACT Exacerbations Progressive loss of lung function None Some limitation Extremely limited 2 days/week >2 days/week Several times per day >80% predicted/personal best * % predicted/personal best <60% predicted/personal best 3-4 N/A /year 2/year (see note) Consider severity and interval since last exacerbation Evaluation requires long-term follow-up care Risk Medication side effects can vary in intensity from none to very troublesome Treatment-related and worrisome. The level of intensity does not correlate to specific levels of adverse effects control but should be considered in the overall assessment of risk. *ACQ Wright, values 2015 of are indeterminate regarding well-controlled asthma. 170 Key: EIB, exercise-induced bronchospasm; FEV 1, forced expiratory volume in 1 second. See figure 3-8 for full name and source of ATAQ, ACQ, ACT. Monitoring Control in Clinical Practice: Asthma Control Test for Patients Aged 12 Years 1 1. Asthma Control Test copyright, QualityMetric Incorporated 2002, All rights reserved. 2. Available at: Accessed February 5, Level of Control Based on Composite Score 2 20 = Controlled = Not Well Controlled 15 = Very Poorly Controlled Regardless of patient s self assessment of control in Question 5 Acute Asthma Exacerbation Management

44 Severity of Acute Exacerbations Acute Asthma Exacerbation Measure FEV1 Inhaled short acting beta 2 agonist: Up to three treatments of 2-4 puffs by MDI at 20 minute intervals OR a single nebulizer Can repeat x 1 2 provided patient tolerates Prednisone What dose and schedule?? accesse 174 Global Strategy for Diagnosis, Management and Prevention of COPD, 2011 COPD REVISED

45 55 year old male Case Study Presents with 3 year history of worsening sob on exertion Present x 10 years Denies chest pain, diaphoresis, lightheadedness Smoker x 35 years; 1 ppd PMH Asthma in childhood ROS Case Study Wheezing with exercise and URI s Sputum production every morning Case Study Physical examination VSS HEENT: normal Heart: S1, S2, RRR; no S3, S4 Lungs: clear but diminished O2 sat 97% on RA Global Strategy for Diagnosis, Management and Prevention of COPD Definition of COPD 1. COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. 2. Exacerbations and comorbidities contribute to the overall severity in individual patients

46 Global Strategy for Diagnosis, Management and Prevention of COPD Risk Factors for COPD Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis and Assessment: Key Points Genes Infections Socio-economic status Aging Populations 181 A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease. Spirometry is requiredto make the diagnosis; the presence of a post-bronchodilator FEV 1 /FVC < 0.70 confirms the presence of persistent airflow limitation and thus of COPD. 182 Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis of COPD SYMPTOMS shortness of breath chronic cough sputum EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution è SPIROMETRY: Required to establish diagnosis 183 Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of Airflow Limitation: Spirometry Spirometry should be performed after the administration of an adequate dose of a shortacting inhaled bronchodilator to minimize variability. A post-bronchodilator FEV 1 /FVC < 0.70 confirms the presence of airflow limitation. Where possible, values should be compared to age-related normal values to avoid overdiagnosis of COPD in the elderly

47 Patient Characteristic Spirometric Classification A B C D Low Risk Less Symptoms Low Risk More Symptoms High Risk Less Symptoms High Risk More Symptoms 185 Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history Exacerbations per year mmrc CAT GOLD < 10 GOLD >2 10 GOLD 3-4 >2 0-1 < 10 GOLD 3-4 >2 >2 10 Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities Use the COPD Assessment Test(CAT) or mmrc Breathlessness scale 186 Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of Symptoms CAT: What are the questions? COPD Assessment Test (CAT): An 8-item measure of health status impairment in COPD ( Breathlessness Measurement using the Modified British Medical Research Council (mmrc) Questionnaire: relates well to other measures of health status and predicts future mortality risk. 187 Reproduced from: COPD Assessment Test Healthcare Professional User Guide

48 Global Strategy for Diagnosis, Management and Prevention of COPD Classification of Severity of Airflow Limitation in COPD* GOLD 1: Mild GOLD 2: Moderate GOLD 3: Severe In patients with FEV 1 /FVC < 0.70: FEV 1 > 80% predicted 50% < FEV 1 < 80% predicted 30% < FEV 1 < 50% predicted GOLD 4: Very Severe FEV 1 < 30% predicted Case Study Spirometry Test Results FEV1 Pre-bronchodilator: 2.22 L (69%) Post bronchodilator: 243 L (76%) Change: 9% FVC Pre: 4.22 L (107%) Post: 4.45 L (113%) Change: 5% *Based on Post-Bronchodilator FEV Case Study Spirometry Test Results FEV1/FVC Pre: 53% Post: 55% CAT score: Patient Characteristic Spirometric Classification A B C D Low Risk Less Symptoms Low Risk More Symptoms High Risk Less Symptoms High Risk More Symptoms 192 Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history Exacerbations per year mmrc CAT GOLD < 10 GOLD >2 10 GOLD 3-4 >2 0-1 < 10 GOLD 3-4 >2 >

49 Stage A Stage B Stage C Stage D What Stage is Our Patient? What Would You Initiate? What would you do? Which medication would you choose?? Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: COPD Medications Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Non-pharmacologic Beta 2 -agonists Short-acting beta 2 -agonists Long-acting beta 2 -agonists Anticholinergics Short-acting anticholinergics Long-acting anticholinergics Combination short-acting beta 2 -agonists + anticholinergic in one inhaler Methylxanthines Inhaled corticosteroids Combination long-acting beta 2 -agonists + corticosteroids in one inhaler Systemic corticosteroids Phosphodiesterase-4 inhibitors Patient Group A B,C, D Essential Recommended Depending on local guidelines Smoking cessation (can include pharmacologic treatment) Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Physical activity Flu vaccination Pneumococcal vaccination Flu vaccination Pneumococcal vaccination Global Initiative for Chronic Obstructive Lung Disease 49

50 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy (Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.) Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy RECOMMENDED FIRST CHOICE Patient A B C D Recommended First choice SAMA prn or SABA prn LAMA or LABA ICS +LABA or LAMA ICS + LABA and/or LAMA Alternative choice LAMA or LABA or SABA and SAMA LAMA and LABA LAMA and LABA or LAMA and PDE4-inh. or LABA and PDE4-inh. ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and LABA or LAMA and PDE4-inh. 197 Other Possible Treatments Theophylline SABA and/or SAMA Theophylline SABA and/or SAMA Theophylline Carbocysteine SABA and/orsama Theophylline GOLD 4 GOLD 3 GOLD 2 GOLD 1 C A ICS + LABA or LAMA SAMA prn or SABA prn ICS + LABA and/or LAMA LABA or LAMA CAT < 10 CAT > 10 mmrc 0-1 mmrc > Global Initiative for Chronic Obstructive Lung Disease D B 2 or more or >1 leading to hospital admission 1 (not leading to hospital admission) 0 Exacerbations per year Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy ALTERNATIVE CHOICE Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy OTHER POSSIBLE TREATMENTS GOLD 4 GOLD 3 GOLD 2 GOLD 1 C A LAMA and LABA or LAMA and PDE4-inh or LABA and PDE4-inh LAMA or LABA or SABA and SAMA D ICS + LABA and LAMA or ICS + LABA and PDE4-inh or LAMA and LABA or LAMA and PDE4-inh. LAMA and LABA B 2 or more or >1 leading to hospital admission 1 (not leading to hospital admission) 0 Exacerbations per year GOLD 4 GOLD 3 GOLD 2 GOLD 1 C SABA and/or SAMA Theophylline A Theophylline D Carbocysteine SABA and/or SAMA Theophylline B SABA and/or SAMA Theophylline 2 or more or >1 leading to hospital admission 1 (not leading to hospital admission) 0 Exacerbations per year CAT < 10 CAT > 10 mmrc 0-1 mmrc > Global Initiative for Chronic Obstructive Lung Disease CAT < 10 CAT > 10 mmrc 0-1 mmrc > Global Initiative for Chronic Obstructive Lung Disease 50

51 Long-term oxygen therapy Goal To ensure adequate oxygen delivery to the vital organs by increasing the baseline PaO 2 at rest to => 60 mm Hg at sea level and/ or producing a SaO 2 => 90%. Long-term oxygen therapy Indications to initiate long-term (> 15 hours/day) oxygen therapy PaO2< 55 mm Hg orsao2< 88% with or without hypercapnia PaO mm Hgor SaO2= 89% in the presence of cor pulmonale, right heart failure, or polycythemia (hct> 56%) Source- Utilized with permission from Fitzgerald Health Education Associates, Utilized with permission from Fitzgerald Health Education Associates, Exercise training Nutrition counseling Education Pulmonary Rehab Conducted over 6 weeks Improves exercise performance and reduces dyspnea (no improvement on FEV1) Surgery Bullectomy Lung Volume Reduction Surgery Lung transplant surgery

52 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations An exacerbation of COPD is: an acute event characterized by a worsening of the patient s respiratory symptoms that is beyond normal dayto-day variations and leads to a change in medication. 205 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Key Points The most common causes of COPD exacerbations are viral upper respiratory tract infections and infection of the tracheobronchial tree. Diagnosis relies exclusively on the clinical presentation of the patient complaining of an acute change of symptoms that is beyond normal day-today variation. The goal of treatment is to minimize the impact of the current exacerbation and to prevent the development of subsequent exacerbations. 206 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Key Points Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics are usually the preferred bronchodilators for treatment of an exacerbation. Systemic corticosteroids and antibiotics can shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay. COPD exacerbations can often be prevented. 207 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Treatment Options Oxygen: titrate to improve the patient s hypoxemia with a target saturation of 88-92%. Bronchodilators: Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics are preferred. Systemic Corticosteroids: Shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay. A dose of mg prednisolone per day for days is recommended

53 New Information Emerging 40 mg daily x 5 days may be all that is necessary for exacerbation of COPD Equal outcomes Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Treatment Options Antibiotic should be given to patients with: Three cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence. Who require mechanical ventilation Group A Patient characteristics Likely pathogens Recommended ABX Mild exacerbation No risk factors for poor outcome Comorbidities Severe COPD Frequent exacerbations Antimicrobial use within past 3 months Adapted from accessed Gram-positive S. pneumoniae Gram-negative H. influenzae M. catarrhalis Viruses Atypical pathogens C. Pneumoniae First options PCN Amoxicillin Tetracycline TMP/SMX Second option Amox/Clav Azithromycin Clarithromycin Cephalosporins Cefuroxime Cefpodoxime Cefprozil 211 Group B Patient characteristics Likely pathogens Recommended ABX Moderate exacerbation HAS risk factors for poor outcome Comorbidities Severe COPD Frequent exacerbations Antimicrobial use within past 3 months Adapted from accessed Gram-positive S. pneumoniae Gram-negative H. influenzae M. catarrhalis Viruses Atypical pathogens C. Pneumoniae Plus DRSP K. Pneumoniae E. Coli Proteus Enterobacter First option Amox/Clav Second options Fluoroquinolones Gemifloxacin Moxifloxacin Levofloxacin

54 Group C Patient characteristics Likely pathogens Recommended ABX Severe exacerbation HAS risk factors for poor outcome Comorbidities Severe COPD Frequent exacerbations Antimicrobial use within past 3 months Adapted from accessed Gram-positive S. pneumoniae Gram-negative H. influenzae M. catarrhalis Viruses Atypical pathogens C. Pneumoniae Plus DRSP K. Pneumoniae E. Coli Proteus Enterobacter P. aeruginosa First option IV antimicrobials only 213 Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Indications for Hospital Admission Marked increase in intensity of symptoms Severe underlying COPD Onset of new physical signs Failure of an exacerbation to respond to initial medical management Presence of serious comorbidities Frequent exacerbations Older age Insufficient home support 214 Valves Cardiology Valves Tricuspid- between right atrium and right ventricle Mitral- between left atrium and left ventricle Aortic- between left ventricle and aorta Pulmonic-between right ventricle and pulmonary artery 215 Wright,

55 Anatomy and Physiology Anatomy and Physiology Sequence of Valve Closure 1. Systole: Period of ventricular contraction During systole, the pressure in right and left ventricles increases This causes the blood to be ejected from the ventricles into the pulmonary artery and the aorta The aortic and pulmonic valves are open to allow emptying and the mitral and tricuspid valves are closed to prevent regurgitation of blood during the contraction Sequence of Valve Closure 2. Diastole: Period of ventricular relaxation During diastole, the pressure in right and left ventricles decreases This allows the chambers of the heart to fill The aortic and pulmonic valves are closed to prevent blood from escaping and the mitral and tricuspid valves are open to allow filling Wright, Wright, Cardiac Physical Examination Auscultation Locations Auscultate in 5 locations with the bell and the diaphragm Aortic-2nd ics, right sternal border Cardiac Physical Examination Pulmonic-2nd ics, left sternal border Erb s point-4th ics, left sternal border Tricuspid- 5th ics, left sternal border Mitral- 5th ics, left midclavicular line Wright, Wright,

56 Cardiac Physical Examination Cardiac Physical Examination Heart Sounds S1: Mitral and Tricuspid closure Abnormally loud: Mitral stenosis S2: Aortic and Pulmonic closure Physiologic split: common, widens with inspiration Fixed split: ASD, pulmonary stenosis S3: Early diastole 2 types: Physiologic and Pathologic Wright, Wright, S3 Heart Sound S3 Heart Sound Physiologic Heard in about 1/3 of children under 16 Rarely in adults over 30 Pathologic To differentiate from physiologic, correlate with history and physical examination findings Sign of poor cardiac output Seen with CHF Wright, Wright,

57 S3 Heart Sound S4 Heart Sound Caused by an increase in the volume flowing into a ventricle Often related to systolic dysfunction Pathologic S3 unusual in children Known as an atrial gallop Late diastole Physiologic and Pathologic Physiologic Virtually never seen except in exceptionally trained athletes (50% of pro basketball players, runners) Wright, Wright, S4 Heart Sound Click Pathologic Poor ventricular compliance Systolic in timing Mid-late systolic click: MVP Early systolic click: Mitral stenosis Long-standing hypertension, CHF, Angina, HCM Wright, Wright,

58 Murmur Murmurs are often described using 7 characteristics These help the health care professional to figure out possible causes of the murmur Qualities of a Heart Murmur 1. Timing When does it occur? Systole, diastole or continuous Wright, Wright, Qualities of a Heart Murmur 2. Shape Is there a change in the intensity of the murmur Crescendo, decrescendo, both 3. Location Where do you hear it loudest? Qualities of a Heart Murmur 4. Radiation Does it radiate anywhere? Aortic-neck; mitral-axilla Wright, Wright,

59 Qualities of a Heart Murmur 5. Intensity How loud is the murmur? Graded on a roman numeral scale or I through VI Intensity Grade I: Very faint, barely audible Grade II: Soft, quiet but easily heard Grade III: Moderately loud; no thrill Murmur is as loud as S1 and S2 Wright, Wright, Intensity Grade IV: Loud, thrill is present Grade V: Very loud, thrill is present Grade VI: Able to be heard with stethoscope off chest; thrill is present Qualities of a Heart Murmur 6. Pitch Also called frequency Low, medium or high pitched 7. Quality What does the murmur sound like? Blowing, musical, harsh, rumbling, humming, buzzing Wright, Wright,

60 Heart Murmurs Systolic MR PASS MVP Diastolic MS ARD Hypertension Source -Fitzgerald Health Education Associates, 2012 Wright, Impact of Hypertension Hypertension is the most common condition seen in primary care 50 million individuals in the United States have hypertension 1 277,000 deaths annually in US due to hypertension 2 1 American Association of Clinical Endocrinologists Medical Guidelines For Clinical Practice for the Diagnosis and Treatment of Hypertension. Endocrine Practice, Vol 12 No. 2 March/April National Center for Health Statistics. Health, United States, 2005, with Chartbook on the Health of Americans. Hyattsville, Maryland: Available at: Hypertension Remains One of the Most Important Multipliers of CV Risk BP >140/90 mm Hg is associated with: 277,000 deaths in 2003 BP, blood pressure; CHF, congestive heart failure; MI, myocardial infarction. Rosamond W et al. Circulation. 2007;115:

61 It is currently estimated that 90% of normotensive 55 year olds will develop hypertension at some point in his/her lifetime Hypertension and Management: Old School Hypertension = Systemic disease Hemodynamics altered Treat the blood pressure Therapeutic options Beta Blockers ACE ARB Diuretics CCB Others 241 Adapted Wright, from 2015 Vascular Biology Working Group, University of Florida 242 College of Medicine, Carl Pepine, MD, Director Hypertension and Management: New School Beta Blockers Hypertension = Disease of the blood vessels Vascular biology altered Treat the vasculature Therapeutic options ACE ARB Diuretics CCB Others Adapted Wright, from 2015 Vascular Biology Working Group, University of Florida 243 College of Medicine, Carl Pepine, MD, Director Case Study: MS 62 year old white female presents today for a complete PE Feeling well without complaints Last visit in clinic 3 months ago VS: 97.9, 84 bpm, 16 respirations/min, BP 152/94 BMI: 32 Eye: retinal examination normal AAO, smiling, conversant Carotids: 2+ bilaterally, no bruits Heart: S1S2, RRR, no S3, S4, murmurs PV: DPPT 2+ bilaterally without edema

62 Today: Diagnosis 3 months ago: Obesity Elevated blood pressure without diagnosis of hypertension (796.2) 245 Patient: MS 62 year old white female presents today for a complete PE Feeling well without complaints Todays visit VS: Pulse: 88 bpm, BP 160/96 mm/hg BMI: 32 Eye: retinal examination normal AAO, smiling, conversant Carotids: 2+ bilaterally, no bruits Heart: S1S2, RRR, no S3, S4, murmurs PV: DPPT 2+ bilaterally without edema 246 Diagnosis Do We Have a Diagnosis of Hypertension? 2 readings; separated apart Patient should not ingest caffeine or smoke for 30 minutes before readings Patient should sit for 5 minutes with arm at heart level before blood pressure is checked

63 With Today s Diagnosis JNC VIII CBC CMP TSH Lipid profile Urine dip Made numerous recommendations regarding treatment The following slides will present these recommendations: Downloaded From: on 01/19/ Recommendation 1 In the general population aged > 60 years, initiate pharmacologic treatment to lower BP at systolic blood pressure (SBP) of 150 mmhg or higher or diastolic blood pressure (DBP) of 90mmHg or higher and treat to a goal SBP lower than 150mmHg and goal DBP lower than 90mmHg Case Study: MS > 60 years of age 2 readings confirm diagnosis Benign Essential Hypertension Downloaded From: on 01/19/

64 Recommendation 2 In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP of 90 mm Hg or higher and treat to a goal DBP of lower than 90mmHg Recommendation 3 In the general population < 60 years, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher and treat to a goal SBP of lower than 140mmHg. Downloaded From: on 01/19/ Downloaded From: on 01/19/ Recommendation 4 In the population >18 years or older with CKD, initiate pharmacologic treatment to lower BP at SBP of 140mmHg or higher or DBP of 90mmHg or higher and treat to goal SBP of lower than 140mm Hg and goal DBP lower than 90mmHg Recommendation 5 In the population >18 years or older with diabetes, initiate pharmacologic treatment to lower BP at SBP of 140mmHg or higher or DBP of 90 mm Hg or higher and treat to a goal SBP of lower than 140mmHg and goal DBP lower than 90mmHg. Downloaded From: on 01/19/ Downloaded From: on 01/19/

65 Update: Addendum According to AHA, while a target of less than 140/90 is reasonable to avoid heart attacks and strokes, a lower target of less than 130/80 may be appropriate in some individuals with heart disease who have already experienced a stroke, heart attack, or mini-stroke (also called a transient ischemic attack or TIA) or who have other cardiovascular conditions such as a narrowing of leg arteries or abdominal aortic aneurysm. Update The new statement targets a blood pressure goal of less than 150/90 mm Hg for CAD patients who are more than 80 years old accessed accessed Treatment of Hypertension What to do with her? Case Study: MS Lifestyle recommendations were provided 3 months ago No significant changes were made BP remains elevated

66 Pharmacologic Treatments No comment in JNC VIII Lifestyle Modifications to Manage Hypertension 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) Modification Recommendation Systolic Diastolic Chgs Weight Reduction BMI mm/10 kg wt loss Adopt DASH eating Diet rich in fruits 8-14 mm Hg vegetables and low fat with reduced saturated and total fat Dietary Sodium 2.4g Na 2-8 mm Hg Physical Inactivity Brisk exercise 30 day 4-9 mm Hg most days of week Moderation of Alcohol intake 2 drinks day max 2-4 mm Hg 24 oz beer; 10 oz wine 2 oz 100 proof whiskey JAMA. 2003:289: JAMA. 2013;():. doi: /jama

67 Case Study: MS Treatment recommendation for her: CCB, Thiazide, ACE or ARB Clinician choice of medication/class of agent Suggestion: Look at other risk factors and attempt to optimize treatment Lisinopril 10 mg once daily was my choice Treatment Recommendation In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensinconverting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). Downloaded From: on 01/19/ Treatment Recommendation In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB Treatment Recommendation In the population aged 18 years or older with CKD and hypertension, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. Downloaded From: on 01/19/2014 Downloaded From: on 01/19/

68 : 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) What About Other Antihypertensives? When Do You Use? Downloaded From: on 01/19/ Combination Therapy Multiple Antihypertensive Agents Are Needed to Achieve Target BP No. of antihypertensive agents Trial Target BP (mm Hg) UKPDS DBP <85 ABCD DBP <75 MDRD MAP <92 HOT DBP <80 AASK MAP <92 IDNT SBP <135/DBP <85 DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Bakris GL et al. Am J Kidney Dis. 2000;36: Lewis EJ et al. N Engl J Med. 2001;345:

69 Treatment Recommendation: Combination Therapy Initiate therapy with 2 drugs simultaneously, either as 2 separate drugs or as a single pill combination For instance: start therapy with 2 drugs when SBP is >160 mm Hg and/or DBP is >100 mm Hg, or if SBP is >20 mm Hg above goal and/or DBP is >10 mm Hg above goal If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB) Avoid the combined use of ACEI and ARB Titrate the third drug up to the maximum recommended dose. Downloaded From: on 01/19/ Target Organ Damage Heart LVH, Angina, CHF, MI Brain Stroke or TIA Dementia Chronic Kidney Disease Peripheral Vascular Disease Retinopathy Consider Secondary Causes of Hypertension Pheochromocytoma Sleep apnea Renal artery stenosis Drug-induced Cushing s syndrome Hyperthyroidism Polycystic kidney disease CKD JAMA. 2003:289:

70 Newest Guideline Hyperlipidemia 277 Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Major Recommendations Treatment Options

71 What s New? What s New? Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc What s New? Major Recommendations Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American 284 College of Cardiology (2013), doi: /j.jacc

72 Four Major Statin Benefit Groups Those with clinical ASCVD Those with primary elevations of LDL C >190 mg/dl Those with diabetes aged 40 to 75 years with LDL C 70 to 189 mg/dl and without clinical ASCVD And those without clinical ASCVD or diabetes with LDL C 70 to189 mg/dl and estimated 10-year ASCVD risk >7.5% 285 Let s Start with Clinical ASCVD Definition: Acute coronary syndromes History of MI Stable or unstable angina Coronary or other arterial revascularization Stroke or TIA Peripheral arterial disease presumed to be of atherosclerotic origin Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Let s Start with Clinical ASCVD What to do. High and Moderate Intensity Statins Definitions: Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc

73 High, Moderate and Low- Intensity Statins Let s operationalize: LDL-C >190 mg/dl If yes.high intensity statin: Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Diabetes Aged years with LDL C 70 to 189 mg/dl and without clinical ASCVD What to do: So How Do You Calculate 10-Y ASCVD Risk? Tools available to calculate risk: Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc

74 Last Statin Benefit Group HMG CoA Reductase Inhibitors Action Inhibit the HMG CoA reductase enzyme Enzyme is essential for the synthesis of cholesterol Also increases the uptake of LDL by the liver Additional properties: Smooth muscle cell proliferation, platelet aggregation and deposition, fibrinogen, endothelial vasodilation and blood viscosity are also affected by the statins Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American 293 College of Cardiology (2013), doi: /j.jacc Statins: LDL Lowering at Various Doses From Package Inserts Recent Landmark Coronary Prevention Studies Lova 20 mg=29% 40 mg=31% 80 mg=48% Mevacor Prava 10 mg=19% 20 mg=29% 40 mg=34% 80 mg=48% Pravachol Simva 10 mg=28% 20 mg=35% 40 mg=40% 80 mg=48% Zocor Fluva 20 mg=17% 40 mg=23% 80 mg=33% Lescol Atorva 10 mg=38% 20 mg=46% 40 mg=51% 80 mg=54% Lipitor Rosuva 5 mg=43% 10 mg=50% 20 mg=53% 40 mg=62% Crestor Pitava Livalo 1 mg=30% 2 mg=36% 4 mg=45% The Lancet 1994;344: JAMA 1998:279: N Engl J Med 1995;333: N Engl J Med 1998;339: N Engl J Med 1996;335: * Nonfatal MI/CHD death Primary Prevention Secondary Prevention ** Normal cholesterol levels 74

75 Important Information Statins may increase risk of diabetes Studies now confirm this in both men and women No longer need to monitor liver enzymes on scheduled basis; clinician judgement CK Measurement Baseline measurement of CK is reasonable for individuals believed to be at increased risk for adverse muscle events based on a personal or family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that might increase the risk for myopathy. 297 Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc NO Longer Are We. Treating to a target LDL, HDL or triglycerides The RCT evidence clearly shows that ASCVD events are reduced by using the maximum tolerated statin intensity in those groups shown to benefit. After a comprehensive review, no RCTs were identified that titrated drug therapy to specific LDL C or non-hdl C goals to improve ASCVD outcomes. What About Other Agents?? The Expert Panel did find RCT evidence that use of therapy (e.g., niacin) to additionally lower non-hdl C, once an LDL C target was achieved, did not further reduce ASCVD outcomes Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc

76 Essentially. The following medications should be used for those who are completely statin intolerant Cholesterol absorption inhibitors Nicotinic acid Bile acid sequestrants Fibrates and Omega 3 Or.who have poor response to statins, despite maximal therapy and are in the highest risk groups (ASCVD, Diabetes, LDL-C >190 mg/dl) If benefits outweigh risk and keeping in mind, no evidence to support risk reduction Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D, Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Cardiac Warning Signs 302 Hypertrophic Cardiomyopathy Most common cause of sudden cardiac death in the athlete Second: Coronary Artery Abnormalities Third: LVH A few well-known sports figures have died from this disease Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Cardiomyopathy: disease of cardiac muscle Can presents in young adulthood accessed accessed

77 Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Septalthickening and abnormal movements of the mitral valve; Often is accompanied by outlet obstruction Etiology Strong genetic component: Autosomal dominant Often times, family history of individuals dying prematurely as early as in the 20 s accessed accessed Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Clinical Symptoms DOE Often asymptomatic and die spontaneously during exercise Timing: Mid-systolic Location: Left sternal border Radiation: Down left sternal border; occas. carotids Intensity: Grade II and louder/vi accessed accessed

78 Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Quality: blowing, moderately harsh Aids to Diagnosis Decreases with squatting, hand grip Increases with standing, valsalva Associated Findings Rapid upstroke of the carotid impulse accessed accessed Endocrinology Diabetes

79 Screening According to the ADA, screening should begin on all individuals 45 years of age and older 1 Repeated q 3 years if normal If at risk, can begin screening at an earlier age I.e. obese, sedentary lifestyle **American College of Endocrinology 1 : Begin screening at age 25 years, in at risk individuals A 1 C Recommendations: A1C may be used for screening >6.5% - consistent with diabetes 5.7% - 6.4%: prediabetes Group of metabolic diseases characterized by hyperglycemia Results from eight defects Diabetes Decreased insulin secretion Inefficient glucose uptake (skeletal muscle) Increased hepatic glucose production Decreased incretin effect Increased glucagon secretion Increased free fatty acids Neurotransmitter dysfunction Increased glucose resorption 315 DeFronzo RA. Diabetes. 2009;58: Statistics Regarding Prediabetes In 2012, 86 million Americans age 20 and older had prediabetes This is up from 79 million in 2010 The percentage is up slightly, from 35% in 2010 to 37% in 2012 and is now at 51% among those age 65 and older Approximately, 11% of individuals with prediabetes develop type 2 diabetes each year over a 3 year study 2 Majority of individuals with prediabetes develop type 2 diabetes within 10 years accessed accessed 01/28/07 79

80 Statistics Regarding Diabetes In 2012, 29.1 million Americans, or 9.3% of the population, had diabetes In 2010 the figures were 25.8 million and 8.3%. The prevalence rate for adults age 20 and older in 2012 was 12.3%, compared to 11.3% in Increasing by 1 2 million people per year Cost: 1 in every 5 dollars spent in United States in spent on diabetes care/costs 2015 The BMI cut point for screening overweight or obese Asian Americans for prediabetes and type 2 diabetes was changed to 23 kg/m2 (vs. 25 kg/m2) to reflect the evidence that this population is at an increased risk for diabetes at lower BMI. accessed accessed Prediabetes: IFG, IGT, Increased A1C Categories of increased risk for diabetes (Prediabetes)* IFG: FPG mg/dl ( mmol/l) or IGT: 2-h plasma glucose in the 75-g OGTT mg/dl ( mmol/l) or *IFG = Impaired Fasting Glucose *IGT = Impaired Glucose Tolerance A1C % ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S Table 3. Criteria for the Diagnosis of Diabetes Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l)** OR Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT** OR A random plasma glucose 200 mg/dl (11.1 mmol/l) OR A1C 6.5%** ** without equivocal evidence of hyperglycemia, repeat to confirm Diabetes Care Volume 37, Supplement 1, January

81 Important to Remember Postprandial hyperglycemia is a significant contributor to A 1 C levels, particularly at the lower end of A 1 C s For instance: A 1 C of 7.3% to 9.2%: postprandial glucose accounts for 50% of this number A 1 C < 7.3%: postprandial glucose accounts for 70% of this number Take away message someone with an A 1 C of 6.8% - look very closely at reducing postprandial glucose Monnier L, Lapinski, H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: Variations with increasing levels of HbA(1c). Diabetes Care. 2003;26: Treatment of Patient Based on A I C A1C is less than 7.3% A1C is 7.3% - 9.2% Monnier L, Lapinski, H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: Variations with increasing levels of HbA(1c). Diabetes Care. 2003;26: ADA-EASD Position Statement: Management of Hyperglycemia in T2DM ANTI-HYPERGLYCEMIC THERAPY Therapeutic options: Lifestyle - Weight optimization - Healthy diet A_EASD_2012.full.pdf accessed Increased activity level Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin 81

82 DPP: Benefit of diet/exercise or metformin on diabetes prevention in at-risk patients N = 3234 with IFG/IGT without diabetes Cumulativ e incidence of diabetes (%) Placebo Metformin 31% Lifestyle 58% P < < DPP: Benefit of diet/exercise or metformin on diabetes by race/ethnicity N = 3234 with IFG/IGT and without diabetes Reduction in new-onset diabetes (%) White n = 1768 African American n = 645 Hispanic n = 508 America n Indian n = 171 Asian n = Years -80 Lifestyle vs placebo Metformin vs placebo Lifestyle vs metformin DPP Research Group. N Engl J Med. 2002;346: DPP Research Group. N Engl J Med. 2002;346: ADA Guidelines 2015 AACE Type 2 Diabetes Guidelines accessed Rodbard HW et al. Endocr Pract. 2009;15(6):

83 AACE Type 2 Diabetes Guidelines Recommendations: Prevention/Delay of Type 2 Diabetes Refer patients with IGT (A), IFG (E), or A1C % (E) to ongoing support program Targeting weight loss of 7% of body weight At least 150 min/week moderate physical activity Follow-up counseling important for success (B) Based on cost-effectiveness of diabetes prevention, third-party payers should cover such programs (E) Consider metformin for prevention of type 2 diabetes if IGT (A), IFG (E), or A1C % (E) Especially for those with BMI >35 kg/m 2, age <60 years, and women with prior GDM (A) In those with prediabetes, monitor for development of diabetes annually (E) Rodbard HW et al. Endocr Pract. 2009;15(6): ADA. IV. Prevention/Delay of Type 2 Diabetes. Diabetes Care 2012;35(suppl 1):S16. Class Mechanism Advantages Disadvantages Cost Biguanides SUs / Meglitinide s TZDs α-gis Activates AMP-kinase Hepatic glucose production Closes KATP channels Insulin secretion PPAR-γ activator insulin sensitivity Inhibits α glucosidase Slows carbohydrate absorption Extensive experience No hypoglycemia Weight neutral? CVD Extensive experience Microvasc. risk No hypoglycemia Durability TGs, HDL-C? CVD (pio) No hypoglycemia Nonsystemic Post-prandial glucose? CVD events Gastrointestinal Lactic acidosis B-12 deficiency Contraindications Hypoglycemia Weight gain Low durability? Ischemic preconditioning Weight gain Edema / heart failure Bone fractures? MI (rosi)? Bladder ca (pio) Gastrointestinal Dosing frequency Modest A1c Low Low High Mod. Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of Table 1. Properties of anti-hyperglycemic agentsprint] Class Mechanism Advantages Disadvantages Cost DPP-4 inhibitors GLP-1 receptor agonists Amylin mimetics Bile acid sequestrants Dopamine- 2 agonists Inhibits DPP-4 Increases GLP-1, GIP Activates GLP-1 R Insulin, glucagon gastric emptying satiety Activates amylin receptor glucagon gastric emptying satiety Bind bile acids Hepatic glucose production Activates DA receptor Modulates hypothalamic control of metabolism insulin sensitivity No hypoglycemia Well tolerated Weight loss No hypoglycemia? Beta cell mass? CV protection Weight loss PPG No hypoglycemia Nonsystemic Post-prandial glucose CVD events No hypoglyemia? CVD events Modest A1c? Pancreatitis Urticaria GI? Pancreatitis Medullary ca Injectable GI Modest A1c Injectable Hypo w/ insulin Dosing frequency GI Modest A1c Dosing frequency Modest A1c Dizziness/syncope Nausea Fatigue Table 1. Properties of anti-hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin High High High High High 83

84 Class Mechanism Advantages Disadvantages Cost Insulin Activates insulin receptor peripheral glucose uptake Universally effective Unlimited efficacy Microvascular risk Hypoglycemia Weight gain? Mitogenicity Injectable Training requirements Stigma Variable A1C: 8.5% Weight: 220 pounds Case Study 2 - John Medications: Glimepiride 4 mg once daily Sitagliptin/metformin 50/1000 mg 1 pill two times daily Atorvastatin 40 mg 1 tablet daily Aspirin 325 mg 1 pill once daily Lisinopril/HCTZ 20/25 mg 1 pill once daily Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin Table 1. Properties of anti-hyperglycemic agents Introduction of Insulin ADA 2015 Insulin Type Onset Peak Duration Rapid Acting (Humalog, NovoLog, Apidra) minutes 1 2 hours 3 5 hours Short Acting (Regular) ½ - 1 hour 2 4 hours 4 8 hours Intermediate Acting (NPH) Long-Acting Analogues Glargine (Lantus) Detemir (Levemir) 1-3 hours 4 10 hours hours 2-3 hours 1 hour None None 24 hours+ Up to 24 hours accessed

85 How to Initiate Insulin on John Start with Long-acting at hs 0.2 Units/kg at bedtime 100 kg patient = 220 pounds 0.2 units = 20 units at hs Once above 50 units per day, may find two times daily dosing works best Rapid acting can be added later Typical scale to cover meals: mg/dl 2 units mg/dl 4 units mg/dl 6 units Self-Monitoring Advice 2013 guidelines have modified these recommendations Individualize recommendations Those on intensive insulin therapy should: Test at least before meals, occasionally after eating, at bedtime, before exercise or critical tasks such as driving, when low blood glucose is suspected, and after treating low blood glucose to ensure normoglycemia has been reached Diabetes Care. 2013;36:S1-S110, e1-e4 ADA-EASD Position Statement: Management of Hyperglycemia in T2DM 3. ANTI-HYPERGLYCEMIC THERAPY Glycemic targets - HbA1c < 7.0% (mean PG mg/dl [ mmol/l]) - Pre-prandial PG <130 mg/dl (7.2 mmol/l) - Post-prandial PG <180 mg/dl (10.0 mmol/l) - Individualization is key: Tighter targets ( %) - younger, healthier Looser targets ( %+ ) -older, comorbidities, hypoglycemia prone, etc. Goals for A1C More stringent HbA1c targets (e.g., %) might be considered in select patients Short disease duration, long life expectancy, no significant CVD if this can be achieved without significant hypoglycemia Conversely, less stringent HbA1c goals e.g., % or even slightly higher are appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbid conditions and those in whom the target is difficult to attain PG = plasma glucose - Avoidance of hypoglycemia Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin accessed

86 Management of Hyperglycemia Guidelines for Glycemic, BP, & Lipid Control HbA1C Preprandial glucose Postprandial glucose American Diabetes Assoc. Goals < 7.0% (individualization) blood glucose target of mg/dl < 180 mg/dl Blood pressure < 140/90 mmhg Lipids No longer targeting particular numbers accessed HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides. Diabetes Care 2015;38(Suppl. 1):S4 DOI: /dc15-S003 Hypertension and Diabetes Statins and Diabetes The new ADA recommendation < 140 mm Hg systolic Previously < 130 mm Hg New ADA recommendations do say that a target below 130 mm Hg might be appropriate for certain individuals, such as younger patients, as long as it can be achieved "without undue treatment burden." Diabetes Care. 2013;36:S1-S110, e1-e accessed

87 Recommendations: Antiplatelet Agents Consider aspirin therapy ( mg/day) (C) As primary prevention in type 1 or type 2 diabetics at increased cardiovascular risk (10-year risk >10%) Includes most men >50 years of age or women >60 years of age who have at least one additional major risk factor such as a family history of CVD, HTN, Smoking, Dyslipidemia, Albuminuria Aspirin should not be recommended for CVD prevention for diabetic adults at low CVD risk, since potential bleeding likely offset potential benefits (C) 10-year CVD risk <5%: men <50 and women <60 years of age with no major additional CVD risk factors Thyroid Nodule ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S US and 24-Hour Iodine Uptake Scan Check TSH Cancers are metabolically neutral Ultrasound Helps confirm presence of nodule Scan: Is nodule hot or cold nodule? 15% of nodules identified as cold nodules are malignant 347 Cold Nodule

88 Don... GI and GU Don is a 17 yowm who presents with an 8 hour history of worsening abdominal pain. Woke him from sleep. Epigastric at onset. Now seems lower in right side of abdomen. Associated with nausea and vomiting for the past 2 hours and a temp of 100. Denies bowel changes, urinary symptoms. Meds: none; Allergies: NKDA What is going on with Don? 349 Appendicitis Inflammation/Infection of the Appendix Can lead to ischemia and perforation of the appendix Etiology Most common age: years Incidence: 1.1/1000 Persons each year Males>females Whites>Nonwhites Summer-most common time of year Midwest-highest incidence Appendicitis Mortality and morbidity rates remain high Perforation rates: 17-40% Perforation has been known to occur within 1st hours of the infection 88

89 History of a patient with appendicitis Careful history is the most important aspect Individual is usually a teen or young adult Classic presentation: awakens in the night with vague periumbilical pain Worsens over the period of 4 hours Subsides as it migrates to the RLQ Worsened with movement, deep respirations, coughing History of a patient with Appendicitis Pain precedes anorexia, nausea or vomiting Nausea and anorexia are very common Vomiting may or may not be present Question the diagnosis if patient is hungry Low grade fever or none at all Usually seek attention within hours Patient will often report feeling constipated Clinical Pearl The presence of pain before vomiting is highly suggestive of appendicitis. Diarrhea before pain is more likely to be gastroenteritis. Physical Examination Abdominal Examination Tenderness at McBurney s point 1/3 the distance between the anterior iliac spine and the umbilicus Guarding Contraction of the abdominal walls Frequently present Can be faked or induced 89

90 Physical Examination Rigidity Important predictor of appendicitis Involuntary spasm of the abdominal musculature Caused by peritoneal inflammation Markle s sign Heel-drop jarring test Physical Examination Rebound tenderness Press on area above the pain Suddenly withdraw fingers Rovsing s Sign Pain felt in RLQ when examiner presses firmly in the LLQ and suddenly withdraws Psoas Sign Patient is placed in a supine position Ask patient to lift thigh against your hand that you have placed above the knee Physical Examination Obturator Sign May be or may not be positive Patient is positioned in supine position with the right hip and knee flexed Internally rotate the right leg Internal Examination Laboratory/Radiologic Testing CBC with differential Normal wbc count doesn t rule-out the diagnosis White blood cell count may actually decrease Look for wbc left shift Elevated wbc Elevated neutrophils Elevated bands 90

91 Laboratory/Radiologic Testing Urinalysis Imaging US has reemerged as first line but if negative, proceed with CT (if suspected) US of the right lower quadrant (RLQ) has been shown to be a useful examination because of this technique s safety and high accuracy (approximately 90%) in the diagnosis of acute appendicitis CT may be needed (contrasted) Will decrease the laparoscopy rate Appendicitis IV antibiotics Surgery Treatment accessed With the Introduction of CT Scans Epiploic appendigitis Piece of fat which is twisted Causes significant abdominal pain Most often in upper quadrants of abdomen Michael year old male with a 1 hour history of RUQ abdominal pain that began approximately 1 hour after eating at a steakhouse. Severe; associated with nausea and diaphoresis. Becoming worse since onset. PE-Temp: 99, Pulse-110; BP: 110/88; Abdomen tender in RUQ; No rebound. + BS. What is going on with Michael?

92 Cholecystitis Acutely Inflamed Gallbladder Etiology 20 million Americans affected each year More common in women, fair skinned, obese, 40 Symptoms Colicky pain that begins suddenly and builds to maximum intensity within 1 hour Epigastric or RUQ pain Often radiates to the right scapular region Several hours after a fatty meal Cholecystitis Symptoms Nausea and vomiting are common Physical examination findings Involuntary guarding RUQ Abdominal Tenderness Palpable gallbladder (<1/2 cases) Cholecystitis Physical Examination Findings Murphy s sign Hook left thumb or fingers of right hand under costal margin Inspiratory arrest in response to an increase in pain caused by this maneuver Diagnosis Abdominal ultrasound (6 hours or more of fasting is needed) Treatment Surgical intervention Acalculus Cholecystitis HIDA scan may be needed to assess gallbladder function 92

93 Shaun... Shaun is a 32 year old male who presents with a one week history of worsening abdominal pain located predominantly in the upper abdomen radiating through to the back. Worse with movement. Constant. Becoming progressively worse. Now associated with vomiting and diaphoresis. PE-BP 90/52; 80/50 sitting; Temp ; Pulse 120; Abdomen-tender in LUQ and RUQ. No rebound. What else do we need to know? Pancreatitis Etiology Often a history of alcohol abuse Biliary tract disease May have a history of hypertriglyceridemia (10%) Symptoms Pain is severe and constant; lasting hours-days Develops suddenly and becomes intense in minutes Often radiates to the back (50%) Vomiting is present If not present, consider another diagnosis Pancreatitis Symptoms Pain is worsened by coughing and movement Sweating Physical Examination Tachycardia Postural Hypotension Temperature of degrees Abdominal distension and tenderness Tenderness predominantly in upper quadrants Hypoactive bowel sounds Pancreatitis Laboratory Findings and Diagnosis Amylase: elevated mainly in pancreatic disease Lipase: good confirmatory test Leukocytosis Typically 12,000-20,000 Ultrasound Detect a biliary obstruction caused by gallstones or edema of the pancreas CT scan Best visualization of the pancreas 93

94 Ranson s Prognostic Signs Treatment Admission Age >55 Serum Glucose >200 Serum LDH >350 AST >250 WBC count >16, hours after admission Hct fall >10% BUN rise >5mg/dl Serum Ca <8 Arterial PO2 <60mm Base deficit > 4meq Fluid sequestration >6L Mild Pancreatitis Fasting state until decrease of signs and symptoms (usually within a few days) Cessation of alcohol or correct problem May need IV fluids Moderate -Severe Pancreatitis Hospitalization accessed Paul Paul is a 25yowm who presents with a one-week history of epigastric pain that is worse 2 hours after eating. Pain is sharp, non-radiating. Occasionally awakens him during the night. PMH: Noncontributory Medications: none What do you think is going on with Paul? Peptic Ulcer Disease Affects as many as 10% of the population 350,000 new cases annually Male/Female ratio: 2-1 PUD is mainly the result of an infection not stress or acid production H. pylori is the causative pathogen in 95% of all duodenal ulcers and 80% of gastric ulcers H. pylori is spread by oral-oral route 94

95 H. Pylori More than 50-60% of the world s population is infected with H. pylori. Most common in developing countries and amongst people living in overcrowded situations Greatest risk for infection is in childhood Recurrence rate of peptic ulcer disease is % if H. Pylori is not treated If H pylori is treated-15% recurrence Duodenal Ulcer Etiology Most common ulcer (80% of all peptic ulcers) Peak prevalence: Ages Almost never malignant Symptoms Pain in epigastric-umbilical region Pain is worse approximately 2-3 hours after a meal Frequently awoken by pain; this is very common and suggestive of a duodenal ulcer May radiate to the back Duodenal Ulcer Physical Examination Findings Tenderness in epigastric-umbilical region Diagnosis: Endoscopy is preferred diagnostic option No need for a follow-up study to document resolution Treatment Drug regimen for H. pylori PPI has become standard of care Gastric Ulcer Incidence Peak age % of all peptic ulcers 5% of all gastric ulcers are malignant Symptoms Gnawing sensation in epigastric region Pain occurs before eating, while eating or up to approximately 1 hour after Pain is frequently steady and constant 95

96 Gastric Ulcer Physical Examination Findings Pallor Tachycardia Tenderness in epigastric region Heme positive stools Gastric Ulcer Diagnosis: CBC, H. pylori, and Endoscopy Gastric ulcerations are cancer until proven otherwise Treatment H pylori drug regimen Proton Pump Inhibitor D/C Cigarettes, Alcohol If possible, remove causative agent Shelley Shelley is a 24 yowfwho presents with a 3 day history of vaginal bleeding. Positive pregnancy test in the office 4 days ago. Based upon dates, she is now 5 weeks pregnant. Complaining of LLQ ache and mild cramping. Bleeding has not changed since onset. Serum quant 2 days ago: 100; Today-110. What should we do now? Ectopic Pregnancy Ectopic: pregnancy occurring outside of the uterus Etiology Variety of locations of implantation Average rupture time: 8-12 weeks Most common cause of maternal mortality in the 1st trimester and 2nd leading cause of maternal mortality in the US 1: pregnancies is ectopic 4 fold increase in ectopic rates from

97 Ectopic Pregnancy Ectopic Pregnancy hcg is secreted by the developing trophoblast starting at day 8 of the pregnancy Should double every hours By 6 weeks, the normal hcg is approximately 10,000 Lack of doubling indicates an abnormal pregnancy The woman with an ectopic pregnancy will not have the normal doubling hcg does not go above 6000 Progesterone levels are low <5ng/ml Normal pregnancy: >10ng/ml Clinical Pearl Ectopic Pregnancy The absence of an intrauterine sac on transvaginal ultrasound when the hcg is > 2000 is highly suggestive of an ectopic pregnancy Symptoms Asymptomatic Majority have irregular bleeding Abdominal pain occurs 3-5 weeks after the bleeding begins 97

98 Ectopic Pregnancy Physical Examination Abdominal tenderness (LLQ or RLQ) Uterine size (2/3 will have a normal uterine size) 50% will have an adnexal mass palpable on physical examination Diagnosis of an Ectopic Abdominal examination Pelvic examination Caution: May cause a tubal rupture Urine hcg Serum Quantitative hcg Serum progesterone Transvaginal ultrasound Medical Management of an Ectopic Pregnancy 25% of all ectopic pregnancies can be managed medically 80-90% success rate 80% of individuals treated with MTX will become pregnant again; 11% ectopic Methotrexate injection Conceptus < 3.5cm Unruptured fallopian tube hcg levels <1,500 No fetal heart activity Additional Diagnostic Pearls Kehr s Sign Intense pain of the left shoulder Produced with splenic rupture Will reproduce pain with pressure over spleen but not by palpating left shoulder 98

99 Additional Diagnostic Pearls Gray Turner s Sign Ecchymosis of the flank Indicative of Extra or Intraperitoneal hemorrhage Cullen s sign Periumbilical ecchymosis Indicative of Extra or Intraperitoneal hemorrhage Additional Diagnostic Pearls Pain precedes vomiting in problems requiring surgical intervention Progression of pain from a poorly localized to a localized area warrants a surgical consultation Urinary Tract Infections Most frequently occurring bacterial infection In the US, 8 million visits yearly for UTI s Up to 100,000 hospitalizations Approximately 15% of all antibiotic prescriptions are for UTI s 40% -50% lifetime prevalence in women GrieblingTL. Urinary tract infection in women. In: LitwinMS, SaigalCS, eds. Urologic Diseases in America.Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, D.C.: GPO; NIH publication : Wright, Urinary Tract Infections: Statistics 25-35% of young, sexually active women will have at least one UTI per year Although environmental factors play a role (I.e. failure to void after intercourse), genetics also plays a role First-degree relatives of women with recurrent infection have an increased frequency of UTI s even when there is no anatomical abnormality Believed to be an alteration in the bacteria aggregation sites in the bladder and urethra GrieblingTL. Urinary tract infection in women. In: LitwinMS, SaigalCS, eds. Urologic Diseases in America.Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, D.C.: GPO; Wright, NIH publication :

100 Genetic Predisposition Robust fucosyltransferase activity discourages bacterial adherence within the bladder Also, presence of few bacterial adhesion receptor sites is also thought to be protective Women who have a lot of receptor sites or minimal fucosyltransferase activity tend to have more UTI s particularly from E. Coli and have less lactobacilli in the periurethral region again, making a UTI more likely Pathogenesis Urinary tract is normally sterile Intercourse is often responsible; with increased risk in those who void infrequently Bacterial colonization of the perirectal/vaginal area Bacteria are able to ascend through urethra into bladder Asymptomatic bacterial colonization of bladder Increase in infection rates during pregnancy accessed accessed Wright, accessed accessed Wright, Two Types Two Additional Classifications Uncomplicated Bladder infection or cystitis Complicated Occurs in individuals with structural abnormalities May be asymptomatic or symptomatic May involve the kidneys Consensus Regarding Definition Unfortunately, no true consensus exists regarding a definition but generally thought to be a UTI which occurs in someone at higher risk for an adverse outcomes Wright, Wright,

101 Complicated UTI Definition Infection of the lower or upper urinary tract Presence of a metabolic abnormality, anatomic abnormality, functional abnormality or the presence of a urinary catheter At much greater risk for sepsis or bacteremia 75-overview accessed Wright, Symptoms of Complicated UTI Highly variable May vary from fever only to a myriad of symptoms Dysuria Suprapubic pain Wright, 2014 Urinary frequency and urgency Foul smelling urine Flank pain Fever and chills Rigors Orthostasis 402 Additional Signs and Symptoms: Younger and Older Patient Acute Uncomplicated Cystitis: Pathogens Fever Sepsis Falls Mental status change Increased or new urinary incontinence Hematuria Anorexia Vomiting Gorbach et al, 1999 Guidelines for Infections in Primary Care Wright, Wright,

102 Important Reminders Odor: Rancid or ammonia odor suggests urea-splitting organism (Proteus) Leukocyte esterase May not be present in a neutropenic patient Nitrites Should be conducted on 1 st morning urine Or no void x 1 hour (takes 1 hour for nitrate to nitrite conversion to occur) May be negative in early infection or gram positive organism accessed accessed Wright, Important Reminders ph 5 6: average : acid ph 6.5-8: alkaline ph If alkaline ph: consider urea splitting organism such as Proteus Proteusallows urea to be split into CO2 and ammonia which causes a rise in urine s ph accessed Wright, uuti Urine dip and culture not essential If E. Coli resistance is < 20% and not allergic to sulfa, TMP/SMX DS 1 pill 2x / day x 3 days If E. Coli resistance is >20% or sulfa allergic, nitrofurantoin two times daily x 5 days or fosfomycin one dosage Other options, ciprofloxacin 250 mg one pill two times daily x 3 days 407 Pyelonephritis Infection of the upper urinary tract Associated with fever, flank pain Dysuria Urinary urgency and frequency Symptoms often begin and advance rapidly Diagnosis made: History and physical examination Bacteriuria Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc

103 Pyelonephritis Treatment Options For patient s deemed suitable for outpatient treatment: Obtain urinalysis, culture & sensitivity Obtain blood cultures Antimicrobial therapies Fluoroquinolone (preferred agent) Trimethoprim/sulfamethoxazole (alternative) accessed 04/12/ Mild / Moderate Pyelonephritis Fluoroquinolone x 7-14 days Ciprofloxacin 500 mg 1 po two times daily or ciprofloxacin ER 1000 mg 1 po daily Ofloxacin 400 mg 1 po two times daily Levofloxacin 250 mg once daily TMP/SMX DS 1 po bid x days AM-CL: 875/125 mg po every 12 hours Consider calculi if the individual relapses after treatment Glibert, D., Moerlling, R., Eliopoulos, G., Sande, M. (2008) The Sanford Guide to Antimicrobial Therapy (38th ed.). Sperryville, VA: Antimicrobial Therapy, Inc 410 Importance of Rapid Assessment and Treatment During an acute pyelonephritis, there is a significant and rapid reduction in the perfusion of the kidney Subsequent renal tubular dysfunction and scarring is possible if not treated aggressively and rapidly Always suspect pyelonephritis in any patient with UTI symptoms accessed 04/12/ Severe Pyelonephritis Pathogens E. Coli (>90%) Enterococci Klebsiella Proteus IV antibiotic is recommended (total treatment: 14 days) Hospitalization with blood cultures and septic work-up is essential Glibert, D., Moerlling, R., Eliopoulos, G., Sande, M. (2008) The Sanford Guide to Antimicrobial Therapy (38th ed.). Sperryville, VA: Antimicrobial Therapy, Inc

104 Epidemiology of Osteoarthritis Orthopedics (For strains/sprains, please refer to Pediatric Guidelines) 12% of US adults have symptomatic OA Incidence rises sharply with age By age 75, 80% of people have OA pathology After age 65, female:male ratio = 2:1 Adapted from Lawrence et al Arthritis Rheum. 1998;41: and Felson Epidemiol Rev. 1988;10: Osteoarthritis: Prevalence OA is 30 times more common than rheumatoid arthritis 1 No longer considered a disease of wear and tear Numerous factors predispose the individual to OA 1 Lozada, CJ and Altman, RD in Clinical Care in Rheumatic Diseases, 2 nd Edition, Risk Factors for OA Aging Genetic susceptibility Obesity Quadriceps muscle weakness and knee malalignment Malalignment strong predictor (Valgus) Joint overuse/injury If seen < 40 years of age, almost always traumatic etiology Vocational/sports Low Birth Weight Symptomatic Spine OA Developmental abnormalities Adapted from Felson Epidemiol Rev. 1988;10:1-28 and Brandt. In Harrison s Principles of Internal Medicine. New York: McGraw-Hill; 1998:

105 Pathophysiology of OA No single identifiable cause of OA No longer is degenerative joint disease considered an appropriate description of this condition It is likely caused by a combination of different biochemical, mechanical and genetic factors Pathophysiology Osteoarthritis involves the entire joint Initially cartilage is affected by fibrillations and ulcerations Accompanied by synovial membrane inflammation and the release of inflammatory mediators such as cytokines, interleukin 1B and TNF This causes the production of metalloproteinases which destroy cartilage collagen Ultimately, destroys cartilage and bone structure 1 Lozada, CJ and Altman, RD in Clinical Care in Rheumatic Diseases, 2nd Edition, Normal knee Capsule Cartilage Synovium Bone Normal vs OA Joint Osteoarthritic knee Thickened capsule Cyst formation Sclerosis in subchondral bone Fibrillated cartilage Synovial hypertrophy Osteophyte formation Symptoms of Osteoarthritis Pain is the most common symptom causing an individual to seek evaluation or diagnosis Yet only 40% of individuals with severe radiographic evidence of osteoarthritis suffer from pain 1 Even when pain is present, source of pain is unknown. It is known that damage to joint cartilage is the key feature of OA but is aneural; thus unable to produce pain. Many believe that most of the pain with osteoarthritis is outside of the joint (stretching of the capsule, increased vascular pressure on the subchondral bone, surrounding muscle spasm) Adapted from Brandt. In Harrison s Principles of Internal Medicine. New York: Kellergren JH, Lawrence RC Radiological assessment of osteoarthrosis. Ann Rheum Dis 419 McGraw-Hill; 1998: :

106 Clinical Presentation of OA Symptoms* Pain, initially with use As disease progresses, nighttime pain and pain with rest become more common Stiffness < 30 minutes Gelling may occur: stiffness after inactivity Limitation of motion Muscle weakness Locking or giving way of joints Clinical Presentation of OA Signs Crepitus (sensation of bone rubbing against bone) Bony hypertrophy Bony tenderness Limited range of motion Malalignment Altered gait *Insidious onset. Adapted from Brandt. In Harrison s Principles of Internal Medicine. New York: McGraw-Hill; 1998: *Insidious onset. Adapted from Brandt. In Harrison s Principles of Internal Medicine. New York: McGraw-Hill; 1998: Predominant Sites in OA Hand Finger: distal interphalangeal joints (Heberden s nodes) Finger: proximal interphalangeal joints (Bouchard s nodes) First carpometacarpal and first metatarsophalangeal (bunion) joints Knees Hips Cervical and lumbosacral spine Minor sites Shoulder Elbow Metacarpophalangeal joints (rarely) Radiographic Features Classic Radiographic Findings Joint space narrowing Osteophytes Subchondral cysts Subchondral sclerosis Radiographic severity is believed to relate to clinical severity in < 50% of the patients By the time radiographs reveal significant joint changes, the joint is usually irreversibly altered

107 Radiographic Changes Imaging Kellgren-Lawrence Grading System Most universally accepted Joint space narrowing Osteophytes Subchondral sclerosis Subchondral cysts Diagnosis of Osteoarthritis EULAR 2009 History and Physical Examination Radiographic Findings Official Diagnosis According to the ACR (Knee): Joint pain One of the following Age > 50 Stiffness < 30 minutes Crepitus Osteophytes 6 criteria 3 signs and 3 symptoms Accurate diagnosis 99% of time when all 6 are present Symptoms: Knee pain, limited morning stiffness, reduced function Signs: Crepitus, restricted movement, bony enlargement accessed

108 Comparison of OA and RA Laboratory Markers Osteoarthritis Rheumatoid Arthritis Site(s) affected Localized to joint Articular, systemic, and extra-articular manifestations Pathogenesis Biomechanical; leads to Autoimmune response; loss of cartilage matrix leads to joint destruction Symptoms Pain Pain Stiffness <20 minutes Joint swelling Limited motion Stiffness >1 hour Limited motion Inflammation Usually limited; may Chronic be present in advanced disease Osteophytes Usually present Absent Rheumatoid factor Absent Frequently present Adapted from Brandt. In Harrison s Principles of Internal Medicine. New York: 429 McGraw-Hill; 1998: and Lipsky. In Harrison s Principles of Internal Medicine. New York: McGraw-Hill; 1998: No widespread laboratory markers exist at present that are specific for OA ESR and CRP are not classically elevated with OA Future: biochemical markers Molecules that are released into body fluids during the process of bone destruction and turnover CTX-II: Type II collagen peptide Higher levels are correlated with more rapid destruction of the knee and hip from OA ACR 2012 Hochberg, MC et. al; American College of Rheumatology 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies for Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care & Research, Vol. 64, No. 4, April 2012, pp Management of OA: Treatment Goals Unfortunately, none of the current mainstream medications or therapies for OA halt or slow the progression of this condition Therefore, goals are to: Relieve pain and other symptoms Maintain or improve joint function Minimize disability Enhance quality of life and functional independence Minimize any risks of therapy Educate patients and their families Adapted from Hochberg et al Arthritis Rheum. 1995;38:

109 Management of OA: Nonpharmacologic Options Obesity is the most important modifiable factor causing OA 5% weight reduction resulted in an 18% improvement in functioning For every 1 pound an individual loses 4 pounds of force is reduced on each knee Management of OA: Nonpharmacologic Options Patient education and self-management Exercise Myth: exercise worsens OA needs to be dispelled Care should be taken however to minimize stress on the affected joints Goal: muscle strengthening and stretching Evidence supports: supervised walking, swimming, strengthening programs Swimming: excellent activity for most individuals with OA Lumbar facet OA may be worsened by swimming due to hyperextension of the spine Individuals with chondromalacia patella no bike riding Adapted from Hochberg et al Arthritis Rheum. 1995;38: Management of OA: Nonpharmacologic Options Management of OA: Nonpharmacologic Options 435 Physical Therapy ROM Strengthening Stretching Iontophoresis Phonophoresis Medical directed patellar taping (ACR 2012) Occupational Therapy Bracing Footwear shoe inserts (medially wedged for lateral OA) Canes: can unload stress on the hip by 60% Heel lift Walkers 436 Thermal modalities Thermacare or similar Limited evidence for: Massage Magnets Acupressure or Acupuncture TENS Spa therapy 109

110 2012 ACR Guidelines for OA: Pharmacologic Options Acetaminophen COX-2 specific inhibitor Nonselective NSAID Other pure analgesics Tramadol (Ultram/Ultracet) Opioids Intraarticular injections (corticosteroids) Topical Agents **Choice should be made balancing efficacy and risk Overview: What Is Fibromyalgia? FM is a common chronic widespread pain condition FM patients often have heightened sensitivity to pain (hyperalgesia); in addition, nonnoxiousstimuli may result in pain (allodynia) Patients may present with a wide range of additional symptoms including tenderness, sleep disturbances, fatigue, morning stiffness, cognitive complaints, and mood disorders 437 FM = fibromyalgia. Wolfe et al. Arthritis Rheum. 1995;38:19-28; Staud and Rodriguez. Nat Clin Pract Rheumatol. 2006;2:90-98; Wolfe et al. Arthritis Rheum. 1990;33: ; Henriksson. 438 J Rehabil Med. 2003;(suppl 41): Proposed Etiology of Fibromyalgia Epidemiology of Fibromyalgia Emerging evidence of a genetic component of FM Specific gene mutations may predispose individuals to FM Polymorphisms in the COMT enzyme and the serotonin transporter are potentially associated with FM and other disorders Environmental factors that may trigger the onset of FM Physical trauma or injury Infections (hepatitis C, Lyme disease, parvovirus, EBV) Psychological stressors FM may occur concurrently with arthritis (OA), autoimmune diseases (RA, SLE), and hypothyroidism COMT = catechol-o-methyltransferase; RA = rheumatoid arthritis; OA = osteoarthritis; SLE = systemic lupus erythematosus. Zubieta et al. Science. 2003;299: ; Arnold et al. Arthritis Rheum. 2004;50: ; Clauw and Crofford. Best Prac Res Clin Rheumatol. 2003; 17: ; 439 Burckhardt et al. APS Clinical Practice Guideline Series, No.4. Glenview, IL; Prevalence FM is common worldwide and affects 5 million people or 2%-5% of US adult population Majority of patients between the ages of 35 and 60 years Gender differences Women are more likely to be diagnosed with FM than men (80-90%) Determining FM Prevalence US adult population FM prevalence in US is estimated to be 2%-5% Over 6 million Americans have FM FM is the most common chronic widespread pain condition Wolfe et al. Arthritis Rheum. 1995;38:19-28; Lawrence et al. Arthritis Rheum. 1998;41: ; Wolfe. Am J Med. 1986(suppl 3A);81:7-14; Weir et al. J Clin Rheumatol. 2006;12:

111 Mean total health care cost per patient Fibromyalgia Results in High Levels of Health Care Utilization and Loss of Productivity Health Care Utilization and Costs* Non-FM Patients P<.001 FM Patients STD = short-term disability. *Over a 4412-month period. Berger et al. Int J Clin Pract. 2007;61: ; Brandenburg et al. APS Mean No. STD days per year Short-term Disability (STD) Controls P<.001 FM Patients 3. Finally, a pain signal is sent to the brain from the dorsal horn Pathophysiology of Fibromyalgia: The Role of Central Sensitization 1. First, impulses from afferents depolarize dorsal horn neurons Despite extensive research, the pathogenesis of pain in FM is not clearly understood. However, central sensitization has emerged as a leading theory of disease mechanism. 442 Staud. Arthritis Res Ther [serial online]. 2006;8:208; Henriksson. J Rehabil Med. 2003;41(suppl 41): Then, extracellular Ca 2+ and nitric oxide diffuse into neurons and cause exaggerated release of substance P and glutamate; this results in neuronal hyperexcitability In FM, dorsal horn neurons become hyperresponsive to nociceptive and nonnociceptive somatic stimulation This is known as central sensitization and is thought to result in hyperalgesia and allodynia Fibromyalgia May Be a Central Pain Processing Disorder: fmri Evidence Clinical Features of Fibromyalgia Pain intensity fmri Studies Show Cortical/Subcortical Augmentation of Pain Processing in FM Fibromyalgia Subjective pain control Stimulus pressure control 4.5 WIDESPREAD PAIN Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting TENDERNESS Presence of tender points Most patients also have tenderness to pressure, heat, cold, electrical pain SLEEP DISTURBANCES Characterized by nonrestorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Reduced slow-wave sleep Abnormal alpha wave intrusion in non-rem sleep FATIGUE/STIFFNESS Morning stiffness and fatigue are common characteristics of FM fmri = functional magnetic resonance imaging. Gracely 443 et al. Arthritis Rheum. 2002;46: Stimulus intensity (kg/cm 2 ) Wolfe et 444al. Arthritis Rheum. 1995;38:19-28; Leavitt et al. Arthritis Rheum. 1986;29: ; Wolfe et al. Arthritis Rheum. 1990:33: ; Roizenblatt et al. Arthritis Rheum. 2001;44: ; Harding. Am J Med Sci. 1998;315:

112 Fibromyalgia Is Often Associated With Sleep Disturbances Nonrestorative sleep is a prominent feature of FM FM patients report insomnia, early morning awakenings, and poor-quality sleep Alpha intrusion is a common but nonspecific EEG finding in FM patients May interfere with sleep function and contribute to worsening of pain after sleep Phasic, tonic, and low alpha are subtypes of alpha sleep intrusion observed in patients with FM % of patients FM Patients Who Experienced Worsening of Pain After Sleep P<.001 Diagnosis Is an Essential Component of Successful FM Management Diagnosis of FM improves health satisfaction ACR and Canadian criteria may be used to diagnose FM Broad-based differential diagnosis must be considered, including: SLE, RA, OA, spondyloarthropathies, polymyalgia rheumatica IMPROVEMENT Patient health satisfaction * Baseline Post diagnosis Phasic alpha Tonic alpha Low alpha *Statistically significant versus baseline (P value not provided). EEG = electroencephalogram. 445 Roizenblatt et al. Arthritis Rheum. 2001;44: ; Harding. Am J Med Sci. 1998;315: Goldenberg et al. JAMA. 2004;292: ; Wolfe et al. Arthritis Rheum. 1990:33: ; Jain et al. J Musculoskelet Pain. 2003;11(4):3-107; 446 Hwang and Barkhuizen. Curr Pain Headache Rep. 2006; ; White et al. Arthritis Rheum. 2002;47: ACR criteria History of chronic widespread pain 3 months Patients must exhibit 11 of 18 tender points Widespread pain was found in 97% of patients with FM, compared with 70% in controls FM can be identified from among other rheumatologic conditions with use of ACR criteria Criteria need further refinement as knowledge about FM evolves Wolfe et al. Arthritis Rheum. 1990:33: American College of Rheumatology (ACR) Criteria for FM ACR criteria are both sensitive (88.4%) and specific (81.1%) 447 Canadian Diagnostic Criteria for FM Includes the ACR criteria and evaluates patients based on other symptoms commonly observed in FM (ie, sleep disturbance, fatigue) Chronic widespread pain and tenderness are core diagnostic features Clinical case definition of FM includes evaluation of additional clinical signs and symptoms commonly observed in patients with FM (neurocognitive manifestations, sleep disturbance, fatigue) Allows clinician to evaluate impact of entire clinical spectrum of FM and tailor treatment 448 Jain et al. J Musculoskelet Pain. 2003;11(4):3-107; Mease. J Rheumatol Suppl. 2005;75:6-21; Wolfe et al. Arthritis Rheum. 1990:33:

113 New Clinical Fibromyalgia Diagnostic Criteria mann.org/uploadedfiles/ _Library_Files/MNII/NewF ibrocriteriasurvey.pdf accessed NII/NewFibroCriteriaSurvey.pdf accessed New Criteria Determining Widespread Pain Index (WPI) Score: 0-19 Determine Symptom Severity Score (SS) Part 2a: Score: 0-9 Part 2b: Score: 0-3 Add up score Total score will provide likelihood of FM or other diagnoses NII/NewFibroCriteriaSurvey.pdf 451 accessed Example of Comprehensive Diagnostic Workup for Fibromyalgia Confirm history of chronic, widespread pain for 3 months Physical exam, patient history, laboratory testing Rule out other conditions that may present with chronic widespread pain Administer WPI/SS Confirm diagnosis of fibromyalgia 452 Adapted from Burckhardt et al. APS Clinical Practice Guideline Series, No.4;

114 Management of Fibromyalgia (FM) Most Patients With Fibromyalgia Will Require Multimodal Therapies Nonpharmacologic Aerobic exercise Cognitive behavioral therapy Patient education Strength training Acupuncture Biofeedback Hypnotherapy Pharmacologic Antidepressants Analgesics Anticonvulsants Analgesics Goldenberg et al. JAMA. 2004;292: ; Clauw et al. Best Prac Res Clin Rheumatol. 2003;17: ; Arnold et al. Arthritis Rheum. 2007;56: Nonpharmacologic Therapies* Patient education Intensive patient education in FM has been shown to improve pain, sleep, fatigue, and quality of life in patients with FM Aerobic exercise Exercise may increase aerobic performance and tender point pain pressure threshold, and improve pain Cognitive behavioral therapy (CBT) Some evidence of improvements in pain, fatigue, mood, and physical function *Only nonpharmacologic therapies with strong evidence are noted. Williams et al. J Rheumatol. 2002;29: ; Karper et al. Rehabil Nurs. 2006;31: ; Busch et al. Cochrane Database Syst Rev. 2002;CD003786; 455 Goldenberg et al. JAMA. 2004;292: Tricyclic Antidepressants (TCAs)*: Published Trials 8 Weeks Duration Study Agent N Duration (weeks) Carette et al (1986) AMI vs PBO 70 9 Carette et al (1994) AMI vs CBP vs PBO Ginsberg et al (1996) AMI vs PBO 46 8 Hannonen et al (1998) Heyman et al (2001) Caruso et al (1987) AMI vs Moclobemide vs PBO AMI vs Nortriptyline vs PBO AMI vs Nortriptyline Primary End Point Morning stiffness, pain analog score VAS (pain, sleep, stiffness, fatigue) Pain VAS, TP score VAS (pain, sleep, fatigue) NHP, Sheehan disability Significant Improvement AMI = amitriptyline; VAS = visual analog score; PBO = placebo; CBP = cyclobenzaprine; TP = tender points; NHP = Nottingham Health Profile; NTP = number of tender points; FIQ = Fibromyalgia Impact Questionnaire; VSGI = verbal scale global improvement; CGIC = clinician global impression of change; FDA = United States Food and Drug Administration. Carette et al. Arthritis Rheum. 1986;29: ; Carette et al. Arthritis Rheum. 1994;37:32-40; Ginsberg et al. J Musculoskelet Pain. 1996;4(3):37-47; Hannonen 456 et al. Br J Rheumatol. 1998;37: ; Heymann et al. Clin Exp Rheumatol. 2001;19: ; Caruso et al. J Int Med Res. 1987;15: ; Bennett et al. Arthritis Rheum. 1988;31: ; Arnold LM. In: Wallace & Clauw s Fibromyalgia and Other Central Pain Syndromes. No No Yes Yes NTP, FIQ, VSGI No 60 8 Manual TP count Yes Bennett et al (1988) CBP vs PBO CGIC Yes *No TCAs are currently FDA approved for FM. 114

115 Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)*: Published Trials Analgesics*: Published Trials Study Agent N Study Duration (weeks) Primary End Point Significant Improvement Study Agent N Study Duration (weeks) Primary End Point Significant Improvement Vitton et al (2004) Milnacipran vs PBO Pain intensity (pain diary) Yes Bennett et al (2005) Tramadol/ acetaminophen vs PBO SF-36, FIQ Yes Gendreau et al (2005) Arnold et al (2005) Arnold et al (2004) Dwight et al (1998) Milnacipran vs PBO Duloxetine vs PBO Duloxetine vs PBO Venlafaxine vs PBO Average daily pain score BPI average pain severity FIQ (total and pain) McGill Pain Questionnaire VAS Yes Yes Yes (FIQ total) No (FIQ pain) Yes Bennett et al (2003) Kemple et al (2003) Russell et al (2000) Biasi et al (1998) Tramadol/ acetaminophen vs PBO Opioid Tramadol vs PBO Tramadol vs PBO Time to discontinuation Improvement in pain Time to discontinuation Yes No Yes 12 1 VAS Yes Sayar et al (2003) Venlafaxine vs PBO FIQ Pain score Yes Sorensen et al (1995) Morphine (IV) vs PBO 9 1 Reduction in pain intensity No *. Both publications are based on the same trial. BPI = Brief Pain Inventory; VAS = Visual Analog Score. Vitton et 457al. Hum Psychopharmacol Clin Exp. 2004;19:S27-S35; Gendreau et al. J Rheumatol. 2005;32: ; Arnold et al. Pain. 2005;119:5-15; Arnold et al. Arthritis Rheum. 2004;50: ; Dwight et al. Psychosom. 1998;39:14-17; Sayar et al. Ann Pharmacother. 2003; 37: *No analgesic is currently FDA approved for FM. Doses of morphine equivalent per 24 hour were determined; Single-dose cross-over trial with 1 week washout period. SF-36 = short-form 36; IV = intravenous; VAS = visual analog score. Bennett 458 et al. Arthritis Rheum. 2005;53: ; Bennett et al. Am J Med. 2003;114: ; Kemple et al. Arthritis Rheum. 2003;48:S88; Russell et al. J Clin Rheumatol. 2000;6: ; Biasi et al. Int J Clin Pharmacol Res. 1998;18:13-19; Sorensen et al. Scand J Rheumatol. 1995;24: Anticonvulsants*: Published Trials Study Agent N Arnold et al (2007) Crofford et al (2007) Crofford et al (2005) Arnold et al (2007) Pregabalin vs PBO Pregabalin vs PBO Pregabalin vs PBO Gabapentin vs PBO *Gabapentin is currently not FDA approved for FM. Study Duration (weeks) Primary End Point End point mean pain score Time to loss of therapeutic response End point mean pain score BPI average pain severity score Significant Improvement Published either in peer-reviewed journals or studies included in the Lyrica package insert. Includes 459 open-label phase of trial. Arnold et al. APS, 2007; Crofford et al. APS, 2007; Crofford et al. Arthritis Rheum. 2005;52: ; Arnold et al. Arthritis Rheum. 2007;56: Yes Yes Yes Yes Other Treatments to Correct Sleep and Improve Pain Help to correct sleep issue Consider sleep apnea Trazodone or similar Consider treatment with muscle relaxants, particularly at bedtime (cyclobenzaprine, tizanidine) NSAIDs or acetaminophen provide very little benefit Alpha 2 agonists (eg, clonidine) Dopamine agonists (eg, pramipexole) Consider: tiagabine (Gabitril): 2-12 mg at bedtime Naltrexone: 9 mg 50mg once daily Tramadol 50 mg 100 mg every 8 hours accessed

116 Additional Reported Options Dextromethorphan: anecdotal evidence that it is helpful NMDA receptor antagonist Topical Capsaicin may helpful The selective estrogen receptor modulator raloxifene (Evista), 60 mg every other day has been shown to be effective in improving pain, improving fatigue, reducing tender-point count, and improving daily functioning in postmenopausal women with fibromyalgia Modafinil (Provigil), approved for narcolepsy and shift-work sleep disorder, mg in the morning, improves fatigue and cognitive disturbances Beta blocker (propranolol) at bedtime can help with pain Neurologic accessed Migraine Prevalence (American Migraine Study II) There are currently 28 million migraine sufferers age 12+ in the United States 21 million females: approximately 18.2% of women 7 million males: approximately 6.5% of men Migraine prevalence peaks in the age range These are the most productive years of the lifespan One in 4 households has at least 1 migraine sufferer More common than asthma & diabetes combined Migraine Prevalence Disease Prevalence in the US Population Lipton et al. Headache. 2001;41: Data from the CDC, US Census Bureau, and the Arthritis Foundation. 116

117 Migraine Prevalence: US Female Population 10/16/2015 New Insights into Migraine Pathophysiology A Scientific Hypothesis for the Tension-Like and Sinus Like Presentation of Migraine The Migraine Process: Activation of Nerves and Blood Vessels The Migraine Process: Activation of the Trigeminal Nucleus Caudalis (TNC) 117

118 Trigeminal Nucleus Caudalis (TNC): Processing and Relaying Migraine Pain Activation of the TNC can Result in Referred Pain Activation of the TNC May Result in Referred Pain that Could be Perceived Anywhere along the Trigeminocervical Network Activation of the TNC May Result in Reflex Activation of Cranial Parasympathetic Nerves Extending into Sinus Cavities and Tear Ducts Cranial Parasympathetic Activation May Explain Sinus-Like Symptoms in Migraine 118

119 Pathophysiology of Migraine is No Longer Just Neurovascular: Multiple Mechanisms of Migraine Exist Bolay H et al. Nature Medicine. 2001;8(2): Burstein R. Pain. 2001;89: Cady RK and Biondi DM. Postgraduate Medicine. 2006; Suppl (April):5-13. Hargreaves RJ, Shepheard SL. Can J Neurol Sci. 1999;26(suppl3):S Silberstein SD. Cephalalgia. 2004;24(Suppl 2):2-7. Williamson DJ, Hargreaves RJ. Microsc Res Tech. 2001;53(3): Woolf CJ. Ann Intern Med. 2004;140: Using ID Migraine * Prescreening Questions a. Do your headaches limit your ability to work, study, or enjoy life? or b. Do you want to talk to your health care professional about your headaches? Screening Questions During the last 3 months, did you have the following with your headaches: 1. You felt nauseated or sick to your stomach? Yes No 2. Light bothered you (a lot more than when you don t have headaches)? Yes No 3. Did your headache limit your ability to work, study, or do what you needed to do for at least 1 day? Yes No *Physician disclaimer: Answering the questions in the ID Migraine screener is not intended to provide a medical diagnosis for migraine. Since the ID Migraine screener relies on selfreporting, the health care professional should verify all responses. A definitive diagnosis of migraine is made on clinical grounds by a health care professional taking into account how well the patient understood the questionnaire as well as other relevant information. ID Migraine is a trademark of Pfizer Inc. Patent pending. Lipton RB et al. Neurology. 2003;61: Episodic Migraine Without Aura: Diagnostic Criteria At Least 5 Attacks Fulfilling the Criteria Below Headache attack lasting 4 to 72 hours (untreated or unsuccessfully treated) Not attributable to another disorder Description of Headache Two of the Following: Unilateral location Pulsating quality Moderate or severe intensity (inhibits or prohibits daily activities) Aggravated by or causing avoidance of routine physical activity (eg, walking or climbing up stairs) Olesen J et al. Cephalalgia. 2004;24(suppl 1): AND Associated Symptoms One of the Following: Nausea and or vomiting Photophobia and phonophobia Episodic Migraine with Aura: Diagnostic Criteria At Least 2 Attacks Fulfilling the Criteria Below Meets the IHS criteria for migraine without aura Not attributable to another disorder Three of the Following: Recurrent one or more fully reversible visual, sensory, and/or speech symptoms (focal neurological symptoms) At least 1 aura symptom develops gradually over 5 minutes, or different symptoms occur in succession over 5 minutes Each aura symptom lasts 5 minutes and 60 minutes Migraine headache begins during or within 60 minutes of aura Olesen J et al. Cephalalgia. 2004;24(suppl 1):

120 Level A Recommendations: Effective AHS/AAN Migraine Prevention Guidelines AAN%20Guidelines.pdf accessed Drug Divalproex/sodium valpoate Metoprolol Petasites (butterbur) Propranolol Timolol Topiramate Dosage mg/day mg/day mg two times daily mg/day 10 15mg two times daily mg/day AAN%20Guidelines.pdf accessed Level B Recommendations: Probably Effective Level B Recommendations: Probably Effective Drug Dosage Drug Dosage Amitryptyline mg/day Riboflavin 400 mg daily Fenoprofen mg three times daily Venlafaxine 150mg ER once daily Feverfew 50 mg 300 mg two times daily Atenolol 100 mg daily Histamine 1 10 ng subcutaneously twice weekly Ibuprofen 200 mg two times daily Ketoprofen 50 mg three times daily Magnesium Naproxen/naproxen sodium 600 mg daily 550 mg two times daily AAN%20Guidelines.pdf accessed AAN%20Guidelines.pdf accessed

121 Level C Recommendations: Possibly Effective Level C Recommendations: Possibly Effective Drug Dosage Drug Dosage Candesartan 16mg once daily Mefanamic acid 500 mg three times daily Carbamazepine 600 mg daily Coenzyme Q mg three times daily Clonidine 0.75 mg daily Cyproheptadine 4 mg daily Guanfacine mg/day Lisinopril mg daily Nebivolol 5 mg daily Pindolol Flurbiprofen 10 daily 200 mg daily AAN%20Guidelines.pdf accessed AAN%20Guidelines.pdf accessed DSM IV-TR Diagnostic Criteria for MDD Psychiatric 5 or more symptoms in the same 2-week period on most days (see next slide) 1 of these symptoms must include: Depressed mood, lack of interest or pleasure in most activities (anhedonia) 483 Wright

122 Pneumonic SIG E CAPSfor the Diagnosis of MDD DSM-IV Sleep (or Sex) Interest Guilt Energy Concentration Appetite Psychomotor Suicidal thoughts Wright Wright 2015 Accessed DSM V Major Depressive Disorder Neither the core criterion symptoms applied to the diagnosis of major depressive episode nor the requisite duration of at least 2 weeks has changed from DSM-IV. Accessed DSM IV-TR Diagnostic Criteria for Generalized Anxiety Disorder (GAD) 3 or more symptoms occurring on most days for 6 months or longer Physical: Restlessness or feeling keyed-up Fatigue Muscle tension Psychological: Excessive anxiety or worry* Difficulty controlling worry* Irritability Difficulty concentrating or mind going blank Sleep disturbance Wright 2015 Wright 2015 *Both must be present 122

123 Assessment of Suicidal Risk 1/2 to 2/3 of people who commit suicide have seen a health provider within the month Assessment focus Ideation Plan History of previous attempt History of family or friend s suicide Support system History of social embarrassment Use of Beck Suicide Intent Scale Wright 2015 American Psychiatric Association Guidelines for Treating Depression Acute Phase 1-8 weeks of treatment Goal: Quick remission Treatments: therapy, antidepressants Light therapy, exercise, alternative therapies Continuation Phase 8-20 weeks Goal: Sustaining remission Maintain same dose of medication as with the acute phase Psychotherapy must be continued (enhances recovery); discontinued at end of phase Note: suicide rates increase here Wright 2015 American Psychiatric Association Guidelines for Treating Depression (cont) Maintenance Phase Goal: Prevent relapse This is often when the medications get discontinued (must taper off) Discontinuation of Active Treatment Consider discontinuing medication if this is first episode Decision to discontinue medication must be carefully considered and discussed with patient Wright 2015 Treatment of Depression Goals of Treatment: Reduce/eliminate symptoms Restore function Prevent relapse and recurrence Psychotherapy Cognitive Behavioral Interpersonal Psychodynamic Wright 2015 Drug Therapy SSRI/SNRIs TCAs Other Therapy ECT EMDR Photolight Therapy 123

124 Probability of Recurrent Episodes 100% 50% 0% Depression Can Be a Chronic Illness 50% After 1 Episode 80% After 2 Episodes 90% After 3 Episodes Nonpharmacologic Options Psychotherapy use a familiar therapist EMDR (eye movement desensitization reprocessing) ECT (electroconvulsive therapy) Reduces cortisol levels Biofeedback/relaxation response Reduces cortisol levels Massage therapy Reduces cortisol levels Nutritional therapy Exercise Light box Community groups/support Wright 2015 Wright 2015 Psychotherapy Cogni ve/behavioral focus is on behaviors, thoughts, and emotions Psychodynamic/psychoanaly c me limited, premise is that psychological events are not produced randomly but by causal forces operating in the individual Family therapy family oriented, directed at the group system SSRIs/SNRIs DNRI Pharmacologic Treatment Options Atypical antidepressants Tricyclic antidepressants (TCAs) Norepinephrine/serotonin modulators Combination therapy Wright 2015 Wright

125 Dermatology Case Study S:TM is a 64-year-old Caucasian male who presents with a painful rash located on his right buttock. Describes the rash as red and blistered Has been present x 96 hours and is in for an evaluation because the pain is severe. Pain is 9 on 0 10 scale. Has tried oral OTC medications without significant improvement. Pain is described as a burning sensation; deep in his buttock. Denies precipitating factors. Pain began approx2 days before the rash appeared. Denies fever, chills, new soaps, lotions, changes in medications. Medications: atorvastatin 40 mg 1 po qhs; amlodipine 5 mg 1 po qhs; loratidine10mg 1 po qd; aspirin 81 mg 1 po qam; various vitamins 497 Wright, 2014 Case Study Allergies: NKDA PMH: dyslipidemia; hypertension; obesity, allergic rhinitis Social history: 30 pack year history of cigarette smoking; none x 10 years; Machinist; happily married x 40+ years Case Study O: T:97.8; P: 94; R:18; BP: 148/90 Skin: p/w/d; approximately vesicles located on right buttock overlying an erythematous base; vesicles are clustered but without obvious pattern; no streaking, petecchiae. Few scattered vesicles on posterior aspect of right thigh; no lesions on left buttock or leg Hips: FROM: no tenderness, erythema, masses Wright, 2014 Wright,

126 Case Study O: PE continued Back: From: no tenderness, erythema, masses Abdomen: Soft, large; + BS; no masses, tenderness, hsm Neuro: intact including light touch, pain, vibratory to right lower extremity; heel, toe walking intact + Allodynia Clothing, light touch, cool object + Hyperalgesia Painful stimuli elicited significant pain Examples of Herpes Zoster Wright, 2014 Wright, 2014 Herpes Zoster Wright, 2014 Wright,

127 Herpes Zoster Highly contagious DNA virus which during the varicella infection (primary infection) gains access into the dorsal root ganglia Virus remains dormant for decades and is reactivated when an insult occurs to the individual s immune system Examples: HIV, chemotherapy, illness, stress, corticosteroid usage Incidence and Prevalence 3 million cases of chickenpox yearly Disease of childhood 600,000-1 million cases of herpes zoster each year in the United States Tends to be more of a disease of aging By age 80, 20% of us will have zoster at some point in our lifetime Men = Women Wright, Wright, 2014 Risk Factors Increasing age (50-60 years and beyond) Varicella infection when < 2 years of age Immunosuppression Stress (controversial) Trauma Malignancies 25% of patients with Hodgkin s will develop zoster 1 Goals of Treatment Treat acute viral infection Shorten course Reduce lesions Treat acute pain Prevent complications Postherpetic neuralgia 1 Stankus, S. et. Al. Management of Herpes Zoster and Postherpetic Neuralgia. Am Fam Physician 2000;61: , ) Wright, 2014 Wright,

128 Acute Treatment Options Antiviral Goal: Reduce viral reproduction Corticosteroids Initially postulated that these reduce viral replication; recent studies have not found this to be true However, they do decrease pain Pain Management Topical agents Anti-inflammatory agents Narcotics Postherpetic neuralgia prevention Wright, 2014 Antiviral Treatment Options Ideally, want to begin within the first 72 hours of the eruption as benefits may be reduced if started after that These medications decrease duration of the rash and severity of the pain Studies vary as to how much these products actually reduce the incidence of post-herpetic neuralgia 1 Stankus, S. et. Al. Management of Herpes Zoster and Postherpetic Neuralgia. Am Fam Physician 2000;61: , ) Wright, 2014 Controlled Trials of Antiviral Agents in Herpes Zoster Pain % of patients with PHN at: Acyclovir vs. Placebo Valacyclovir vs. Acyclovir Famciclovir vs. Placebo 3 months 6 months 25% vs. 54% 15% vs. 35% 31% vs. 38% 19.9% vs. 25.7% 34.9% vs. 49.2% 19.5% vs. 40.3% Pain associated with herpes zoster can range from mild severe Clinician must tailor pain medication options based upon individual presentation Adapted from Johnson RW. J Antimicrob Chemother. 2001;47:1-8. Wright,

129 Pain Management Topical Agents Calamine lotion to lesions 2 3x/day Betadine to lesions qd Capsaicin cream once lesions crusted 3 5x/day Topical lidocaine 5% patch for 12 hours at a time once lesions are crusted Acute Pain Management Oral Agents Acetaminophen Has not been shown to be effective in trials) Ibuprofen or similar Not likely to be effective with neuropathic pain Nerve Blocks Have been shown to be effective for many individuals with severe pain in some trials; other trials - ineffective 1 Stankus, S. et. Al. Management of Herpes Zoster and Postherpetic Neuralgia. Am Fam Physician 2000;61: , ) Wright, 2014 Wright, 2014 Diagnosis? Linked with? And the use of medications such as TCA s, gabapentin, pregabalin, oxycodoneand tramadolduring the acute phase of HZ decrease pain but also may also reduce the risk of PHN Wright, 2014 Wright,

130 Dermatofibroma Squamous Cell Carcinoma Wright, 2014 Wright, 2014 Seborrheic Keratosis Basal Cell Carcinoma Wright, 2014 Wright,

131 Malignant Melanoma Squamous Cell Carcinoma Wright, 2014 Wright, 2014 Thank You! I Would Be Happy To Entertain Any Comments or Questions! WendyARNP@aol.com Wendy L. Wright, MS, APRN, FNP, FAANP