1 Lesions, Swelling, Pain and Dysfunction: Men’s Health Update Thomas W. Barkley, Jr., DSN, ACNP-BC Associate Professor of Nursing Director of Graduate and Nurse Practitioner Programs California State University, Los Angeles and President, Barkley & Associates www.NPcourses.com 2 I have no current affiliation or financial arrangement with any grantor or commercial interests that might have direct interest in the subject matter of this CE Program. 3 Objectives Identify common disorders requiring specific pharmacotherapy for select male conditions Recognize common pharmacologic agents prescribed for select male conditions State differences between select male conditions and various pharmacologic therapies specific to each 4 Lesions, Swelling, Pain and Dysfunction: Men’s Health Update Topical Outline Epididymitis Prostatitis Balanitis Benign Prostatic Hypertrophy (BPH) Prostate Cancer Erectile Dysfunction Men’s STIs/STDs Update: 5 Herpes Genitalis Genital Warts Chlamydia Gonorrhea Syphilis Chancroid LGV Men’s Reproductive System 1. Prostate gland: Produces a fluid which forms part of the semen (the liquid which appears as ejaculate) 2. Seminal vesicles: Sit at the back of the prostate gland; produce the thick milky fluid of the semen 3. Vas deferens: Tube which carries sperm from the testicles to the urethra 4. Scrotum: Sac which hold the testicles 5. Urethra: Tube which carries urine from the bladder and semen through the penis 6 Men’s Reproductive System 6. Penis: Made up of spongy tissue which fills with blood during an erection 7. Foreskin: Covers the glans and can be pulled back for cleaning - this is removed when a man is circumcised 8. Glans: Helmet shaped head of the penis 9. Epididymis: Area where sperm are stored in the testicles 10. Testicles: Produce sperm and the male sex hormone testosterone 7 9.3.42 Epididymitis 8 9 Epididymitis Inflammatory reaction of the epididymis caused by either an infectious agent or local trauma Exclusive to males of all ages, but usually found in sexually active men or older males > 600,000 case reported yearly May be caused by congenital urologic structural disorders with possible pre-disposition to infections Epididymitis - Symptoms Dysuria Urgency Frequency Low back/perineal pain Fever/chills Malaise Scrotal edema* 10 11 12 Epididymitis: Signs/Symptoms Tender/painful swelling of the scrotum with erythema Unilateral testicular pain & tenderness + Phren’s test Urethral discharge and/or dysuria Hydrocele or epididymoorchitis (late in condition) Epididymitis Male reproductive organs 1 Ductus deferens 2 Epididymis 3 Testicle 13 Causes & Underlying Factors Young, prepubertal boys: Young, sexually active men: 14 9.3.42 Coliform Bacteria Almost always as a complication of urologic disease Chlamydia trachomatis Neisseria Gonorrhoeae Complications Atrophy of the affected testicle Scrotal abscess Chronic epididymitis Rarely: impaired fertility 15 Epididymoorchitis Types of Epididymitis Bacterial Non Bacterial Tuberculosis Fungal 16 17 18 Bacterial Epididymitis Usually results from an infection spreading to the epididymis from other urogenital organs (e.g., prostate, bladder, kidney, etc.) Quick onset (< 24 hours) Other (Non-Bacterial) Epididymitis Viral: usually with a very quick onset Trauma: initially not associated with fever and generalized symptoms Idiopathic: unknown cause, usually not associated with fever; perhaps caused by rupture of the sperm ducts, causing sperm to leak into the tissue Treatment Pharmacologic: Analgesics Antibiotics 19 Pharmacologic Treatment: Analgesics Acetaminophen with or without Codeine: NSAIDs: 20 For relief of pain and discomfort Ibuprofen Pharmacologic Treatment: Epididymitis Antibiotics In sexually active men: Active agents against N. Gonorrhoeae and Chlamydia should always be included in treatment Ceftriaxone 250 mg IM single dose + Doxycycline 100 mg PO BID x 10 days Azithromycin 1 gm PO single dose If > 35 years of age (older men), consider: Ofloxacin 300 mg p.o. BID x 10 days Levofloxacin 500 mg p.o. every day x 10 days 21 Prostatitis 22 Prostatitis 9.3.42 50% of men experience symptoms of prostatitis in their lifetime ~ 2 million physician visits per year, included a diagnosis of prostatitis Inflammation of the prostate gland Characterized by perineal pain and irregular urination and (if severe) chills and fever 23 Acute Bacterial Prostatitis Infection of the prostate Causative agents: Gram negative bacteria, E. Coli Nonbacterial prostatitis – young men 24 Acute Bacterial Prostatitis Presentation/Exam 25 Fever/Chills Low back pain Dysuria Urgency Frequency Nocturia Acute Bacterial Prostatitis Diagnostic Tests 26 Chlamydia Mycoplasma Gardnerella Urine culture – positive for causative agent Acute Bacterial Prostatitis – Management Hospitalization if septicemia or urinary retention is suspected Possible agents: Trimethoprim Sulfamethoxizole (Bactrim) Ofloxacin Ciprofloxacin Chronic: Finasteride (Proscar) – lowers the amount of testosterone; prostate shrinks; SE: less interest in sex and erectile/ejaculation problems Sitz bath TID for 30 minutes each treatment No sexual intercourse until acute phase resolves 27 Balanitis 28 Balanitis Inflammation of the superficial tissues of the penile head (glans penis) Exclusive to males of all ages, especially sexually active men Uncircumcised men are more at risk for balanitis due to the presence of the foreskin Most of the organisms associated with balanitis are already present on the penis, but in very small numbers 9.3.42 29 30 31 Balanitis Symptoms of Balanitis Itching and tenderness Pain, local edema and dysuria Urethritis with or without discharge Painful erection with altered sexual function Rarely: severe ulcerations which may lead to superimposed bacterial infections Rarely: lymph node enlargement Balanitis: Causes & Risk Factors Poor hygiene Sexual contact Urinary catheters Trauma (frictional or accidental wounds) Allergic reaction to chemical irritants (e.g., soap, lubricant jelly, condoms, etc.) Allergic reaction to medications Obesity 32 33 Types of Balanitis Candidal Trichomonal Mycoplasma Chlamydial Anaerobic Candidal Balanitis Most common type Frequently follows intercourse with an infected partner Also occurs without sexual contact in diabetic patients or patients taking oral antibiotics Recurrent candidal balanitis causes fissuring of the prepuce, with fibrosis and sclerosis 34 Treatment Pharmacologic: Analgesics Ointment & Creams Topical corticosteroids Antibiotics 35 Balanitis: Non-Pharmacologic Treatment Hygiene: 9.3.42 Retraction and bathing of prepuce several times daily Warm sitz baths: If a Foley catheter is used: strict catheter care Ease edema and erythema Circumcision: Consider if symptoms are severe or recurrent May be necessary if phimosis or meatitis occurs 36 Note: Severe phimosis may require prompt slit drainage, if unable to void Pharmacologic Treatment: Analgesics Acetaminophen: for minor pain and fever caused by the skin irritation and infection AND/OR 37 Codeine: for patients with more severe cases or low pain threshold Pharmacologic Treatment Clotrimazole 1% cream: topical cream; kills fungi and yeasts by interfering with their cell membranes Applied to affected areas TID Bacitracin ointment: Topical antibiotic used to treat and prevent bacterial infections. >Applied to affected areas 3 to 4 times daily Topical Corticosteroids: QID for severe dermatitis 38 Balanitis: Considerations 39 40 41 Betamethasone: apply thin film BID Always assess for evidence of other STDs in sexually active men If lesions do not heal, refer for biopsy (i.e., pre-malignant/malignant lesions, carcinoma of the penis, etc.) When possible, always treat underlying cause to avoid future recurrences Even though uncircumcised men are at a higher risk, there is no significant difference in the rate of occurrence, compared to those who are circumcised Benign Prostatic Hypertrophy (BPH) Benign Prostatic Hypertrophy (BPH) Progressive, benign hyperplasia of prostate gland tissue By 50 years, ~ 50% of men By 80 years, ~ 80%-90% of men Etiology is unknown The most common cause of bladder obstruction in men over the age of 50 years BPH – Symptoms (He’s got the ‘goes’ - maybe) 9.3.42 Frequency Urgency Nocturia Dribbling Retention 42 43 44 45 BPH – Physical Exam Bladder distention may be present Prostate is nontender with either asymmetrical or symmetrical enlargement Smooth, rubbery consistency with possible nodules BPH – Diagnostic Tests U/A - rules out UTI, no hematuria Uroflowmetry Abdominal ultrasound - rule out upper tract pathology Serum creatinine/BUN normal American Urological Association-International Prostate Symptom Score (AUA/IPSS) BPH – Diagnostic Tests PSA Normal Levels (Age-specific ranges based on having had a previous PSA < 4 ng/mL) Age 40-49 years: < 2.5 ng/mL Age 50-59 years: < 3.5 ng/mL Age 60-69 years: < 4.5 ng/mL Age 70-79 years: < 6.5 ng/mL 46 BPH – Diagnostic Tests Major Reasons for PSA Elevation: Prostate Cancer Prostate Enlargement Prostatitis 47 Relative Risk of Prostate Enlargement by PSA Level (Wright et al., 2002; http://www.avodart.com/m07_01.html) 48 BPH – Management Observe: Watchful waiting Consult/refer as needed Medications to decrease bulk and/or tone of gland 9.3.42 Alpha-blockers 5-alpha-reductase inhibitors Combination therapy 49 Herbal preparations (saw palmetto?) – not FDA regulated Minimally invasive procedures (numerous) Surgery BPH Pharmacotherapy Alpha adrenergic blockers 50 Originally developed to treat HTN Relax smooth muscle in the prostate and around the bladder neck Similar efficacy Best for normal-sized to moderately enlarged prostates Alpha adrenergic blockers See effects within ~ 1-2 days (increased urinary flow; urinate less often) Often 4 to 6 point decrease in urinary symptom index score Major Side Effects: 51 Decreased ejaculate Low blood pressure Dizziness Headache Stomach or intestinal irritation Stuffy nose Alpha adrenergic blockers Warnings/Considerations: Risk of intraoperative floppy iris syndrome (IFIS) in patients taking tamsulosin (Flomax) or others 52 53 9.3.42 IFIS – characterized by the iris not responding appropriately during cataract surgery Can lower blood pressure to unhealthy levels when taken with erectile dysfunction drugs such as sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) Follow up every 3-6 months during the first year of therapy Enzyme (5-alpha-reductase) inhibitors for BPH Shrink the prostate Reduces the amount of testosterone that turns into dihydrotestosterone (DHT), a hormone required for prostate gland growth Attaches to receptors on the prostate cells; encourages them to grow/multiply Inhibitors reduce the prostate's "appetite" for DHT by reducing the number of receptor sites where DHT can attach 5-alpha-reductase inhibitors for BPH Equally effective Take longer to work ~ 3 – 6 months More costly than alpha blockers Increase urine flow rate Reduce urinary symptom index scores by an average of 3 points 54 5-alpha-reductase inhibitors for BPH With moderate disease to severe disease, may significantly decrease the need for surgery and the incidence of urinary retention Major Side Effects: Erection problems Decreased sexual desire Reduced semen release during ejaculation Side effects may cease when meds are discontinued or after ~ 1 year of therapy 55 56 How safe are the newer 5-alpha-reductase inhibitors? Dutasteride (Avodart) Contraindications: Women and children Patients with known hypersensitivity to 5-reductase inhibitors Warnings/Precautions: Dutasteride is absorbed through the skin Women who are pregnant or may be pregnant should not handle Avodart Soft Gelatin Capsules because of the possibility of absorption of dutasteride and the potential risk of a fetal anomaly to a male fetus (feminization; decreased anogenital distance, nipple development, hypospadias) Women should use caution whenever handling; if contact is made with leaking capsules, the contact area should be washed immediately with soap and water 57 58 Dutasteride (Avodart) Men being treated should not donate blood until at least 6 months have passed following their last dose. Purpose: prevent administration of dutasteride to a pregnant female transfusion recipient Hepatic impairment – not studied PSA reestablished after 6 months – isolated should be doubled after 6 months for comparison to prestudy baseline Dutasteride (Avodart) Adverse events: Impotence Decreased libido Ejaculation disorders Gynecomastia 59 9.3.42 Alpha blockers + 5-alpha-reductase inhibitors Combination Therapy for BPH Most tested: doxazosin + finasteride One study found this combination to significantly reduce the risk of further prostate enlargement to the point where invasive surgery was not needed 60 Works best for those with large prostates and high PSAs Side effects – assumed similar to the combination effect (not significantly studied) Saw palmetto Medicinal element taken from the partially dried ripe fruit of the American dwarf palm tree Studies shown effectiveness in reducing BPH symptoms Appears to have efficacy similar to that of finasteride No known drug interactions Not FDA regulated (Gordon & Shaughnessy, 2003) 61 Prostate Cancer 62 PROSTATE CANCER 63 Most common form of cancer, other than skin cancer, among men in the United States # 2 cause of cancer-related death among men About 70% of all diagnosed prostate cancers are found in men aged 65 years or older Over the past 20 years, the survival rate for prostate cancer has increased from 67% to 97% Death rate higher for African-American men than for any other racial or ethnic group Cause unknown; High-fat diets are implicated Symptoms ASYMPTOMATIC May appear to be BPH In later stages: 64 Bone pain Uremia Prostate Cancer - Examination Adenopathy Bladder distension Prostate palpates harder than normal 65 Prostate Cancer –Tests Prostate-specific antigen (PSA) > 4 abnormal Approximately 40% of prostate cancer patients present with normal PSA values! (not a very sensitive test!) 66 Prostate Cancer – Management 9.3.42 Consult/refer Accurate staging is critical 67 68 Watchful waiting… Treatment options include surgery, radiation, and/or hormone therapy Erectile Dysfunction Erectile Dysfunction (ED) Inability to achieve and sustain an erection suitable for sexual intercourse ~ 52% of men aged 40-70 have ED ~ 5% of 40-year-old men and 15-25% of 65-year-old men experience ED on a long-term basis Not considered “normal” at any age! 69 What Causes Erectile Dysfunction? For an erection to occur: Nerves to the penis must be properly functioning Blood circulation to the penis must be adequate Must be a stimulus from the brain Common causes: atherosclerosis, nerve diseases, psychological factors/stress, depression, performance anxiety, penile injury and medications Causes of ED: Diuretics & Antihypertensives 70 Hydrochlorothiazide (Esidrix, HydroDIURIL, Lotensin) Triamterene (Maxide, Dyazide) Furosemide (Lasix) Bumetanide (Bumex) Methyldopa (Aldomet) Clonidine (Catapres) Verapamil (Calan, Isoptin, Verelan) Nifedipine (Adalat, Procardia) Hydralazine (Apresoline) Captopril (Capoten) Enalapril (Vasotec) Metoprolol (Lopressor) Propranolol (Inderal) Labetalol (Normodyne) Atenolol (Tenormin) Phenoxybenzamine (Dibenzyline) Spironolactone (Aldactone) 71 Causes of ED: Antidepressants, anti-anxiety and antiepileptic drugs Fluoxetine (Prozac) Tranylcypromine (Parnate) Sertraline (Zoloft) Isocarboxazid (Marplan) Amitriptyline (Elavil) Amoxipine (Asendin) Clomiprimine (Anafranil) Desipramine (Norpramin) Nortriptyline (Pamelor) Phenelzine (Nardil) 72 Causes of ED: Antihistamines Dimehydrinate (Dramamine) Diphenhydramine (Benadryl) Hydroxyzine (Vistaril) 9.3.42 Meclizine (Antivert) Promethazine (Phenergan) 73 Causes of ED NSAIDS Naproxen (Anaprox, Naprelan, Naprosyn) Indomethacin (Indocin) Muscle Relaxants Cyclobenzaprine (Flexeril) Orphenadrine (Norflex) Anti-arrythmics Disopyramide (Norpace) 74 Causes of ED H-2 Receptor Antagonists Cimetidine (Tagamet) Nizatidine (Axid) Ranitidine (Zantac) Parkinson’s Disease Medications Biperiden (Akineton) Benztropine (Cogentin) Trihexyphenidyl (Artane) Procyclidine (Kemadrin) Bromocriptine (Parlodel) Levodopa (Sinemet) 75 Causes of ED Recreational Drugs Alcohol Amphetamines Barbiturates Cocaine Marijuana Methadone Nicotine Opiates 76 Erectile Dysfunction: Treatment Medication choices: sildenafil (Viagra) vardenafil (Levitra) tadalafil (Cialis) …known as the phosphodiesterase inhibitors 77 Phosphodiesterase (PDE) inhibitors 9.3.42 Prevent the breakdown of nitric oxide, a chemical messenger that promotes relaxation and opening of the blood vessels that supply erectile tissue in the penis 78 79 Under the influence of nitric oxide, these vessels expand and stay dilated Increased blood flow makes erectile tissue swell and compress the veins that carry blood out of the penis, resulting in a full erection Phosphodiesterase (PDE) inhibitors Erectile Dysfunction: BREAKING NEWS New ED Drugs On The Way! (DeNoon & Chang, 2006) 80 One works fast One lasts long One promises to be the next best thing to a cure! Erectile Dysfunction Near a Cure for Erectile Dysfunction? 81 For now, it is called hMaxi-K Suitably enough for an erection treatment, it is a form of gene therapy called naked DNA Its DNA carries a human genetic code into target cells When the cell reads this code, it makes a protein. In the case of hMaxi-K, it is a protein that tells smooth muscles to relax Erectile Dysfunction First human trial (Melman, 2006) reported 11 men with erectile dysfunction received injections of the gene therapy directly into the penis Because this was the first human study, the doses used were smaller than those expected to have a true effect on erections The study was successful in two ways: 82 It was safe Two men who received higher doses of hMaxi-K had greatly improved erections -- which occurred only during sexual arousal -- for six months after a single treatment! Erectile Dysfunction Additional Findings: 83 Sex doesn’t have to be planned – allows one to get a normal erection whenever aroused hMaxi-K will also be effective for a wide range of diseases that arise from the failure of smooth muscle to relax Overactive bladder Asthma Irritable bowel syndrome BPH Premature labor Premenstrual syndrome Erectile Dysfunction Long Acting Erection Drug, SLx-2101 (Goldstein, 2006) 9.3.42 Like Viagra, Cialis, and Levitra, SLx-2101 works by inhibiting an enzyme that makes smooth muscles contract Unlike other approved erection drugs, SLx-2101 is two drugs in one: 84 When first taken, SLx-2101 is a powerful erection drug While it is still working, the body begins to process it into a second drug, SLx-2101m1, also a powerful erection drug Acts well beyond 48 hours Interestingly, SLx-2101 improves erections not only in men with ED, but also in men already able to have erections! (woo hoo!!) Erectile Dysfunction Faster, Shorter-Acting Erection Drug (Nehra, 2006) Avanafil Avanafil reaches maximum blood concentrations 35 minutes after it is taken It has a half-life of 90 minutes (Compared with 4 hours for Levitra and Viagra and 17.5 hours for Cialis) Good for personal preferences and men who take nitrate-based drugs (e.g., Nitrostat, Isordil, and Imdur) Men taking a nitrate-based drug while on avanafil had less of a drop in blood pressure and less of an increase in blood pressure than men who took the heart drug while on Viagra 85 Men’s STDs/STIs Update 86 Herpes Genitalis 87 Herpes Genitalis Cause: Herpes simplex virus (HSV) types 1 and 2 90-95% of genital herpes caused by type 2 Prevalence: 88 Primary infections ~ 200,000 annually Recurrent infections more common Estimated > 45 million Americans infected 1/5 adolescents (> 12 years old) and adults infected Genital Herpes: Initial Visits to Physicians’ Offices (1996-2004) http://www.cdc.gov/std/stats/tables/table47.htm 89 Herpes Genitalis: Presentation Pruritic vesicles Vesicles rupture to form shallow ulcers Resolve spontaneously Viral shedding occurs intermittently without clinical symptoms 90 91 Genital Herpes What about asymptomatic viral shedding, especially in discordant couples? 92 Genital Warts 93 GENITAL WARTS 9.3.42 Single or multiple soft, fleshing, papillary or sessile, painless keratinized growth around anus, penis, urethra or perineum 94 GENITAL WARTS (Condyloma acuminata) Cause: Human papillomavirus (HPV) Prevalence: 95 The most common symptomatic viral STD in U.S. Accounts for > than 1 million office visits per year Estimated 3 million cases of HPV are reported annually GENITAL WARTS (Condyloma acuminata) Over ½ of sexually active men in the U.S. will have HPV at some time in their lives ~ 1% of sexually active men in the U.S. have genital warts at any one time The incidence of penile cancer is increasing In this country, penile cancer accounts ~ 0.2% of all cancers in men (especially rare in circumcised men) ~ 1,910 men will be diagnosed with anal cancer in 2006 96 GENITAL WARTS Treatment Remove warts 97 Risk is 17 times higher among gay and bisexual men, as well as those with compromised immune systems (HIV) Cryosurgery Trichloroacetic acid (TCA) Bichloroacetic acid (BCA) Laser treatment No therapy has been shown to completely eradicate HPV 98 Chlamydia Chlamydia: Signs/Symptoms 99 Chlamydia Treatment: Azithromycin (Zithromax) 1 g p.o. x 1 dose Doxycycline (Adoxa) 100 mg p.o. BID x 7-10 days NOTE: Due to high rate of coexistence with gonorrhea, both diseases are commonly treated simultaneously 100 9.3.42 Ceftriaxone 125 mg IM x 1 dose Report to Health Department (in most states) Gonorrhea 101 Gonorrhea Cause: Neisseria gonorrheae, a gram-negative diplococcus Prevalence: Most commonly reported communicable disease in the United States Estimated 1.5 million per year 102 Gonorrhea: Symptoms 103 Dysuria Increased frequency of urination Purulent urethral discharge Testicular pain Many to most patients may be asymptomatic Gonorrhea Diagnosis: DNA probe or culture Treatment: Ceftriaxone (Rocephin) 125 mg IM x 1 dose Report to the health department 104 Syphilis 105 Syphilis Cause: Treponema pallidum, a spirochete with 6 to 14 regular spirals Prevalence: 40,000 cases annually in the United States 106 Highest level in the past 40 years Syphilis: Symptoms Primary: Chancre is painless Indurated ulcer Located at the site of exposure 107 Syphilis: Symptoms Latent: Seropositive Asymptomatic 108 Syphilis Chancre 109 Secondary syphilis - palms and soles 110 Syphilis Serologic 9.3.42 Tests: 111 Nontreponemal: VDRL/RPR Treponemal tests: FTA-ABS (fluorescent treponemal antibody absorption MHA-TP (microhemaglutination assay for antibody to T. pallidum) Syphilis: Treatment Primary, secondary or early Benzathine penicillin G - 2.4 million units IM x 1 Late, latent, and indeterminate length, tertiary Benzathine penicillin G - 2.4 million units IM weekly x 3 weeks Penicillin allergic Doxycycline 100 mg p.o. BID or Erythromycin 500 mg p.o. QID Report to health department 112 Chancroid 113 Chancroid Cause: Hemophilus ducreyi, a gram-negative bacillus Symptoms Women - usually asymptomatic Men - single (though may be multiple) superficial, painful ulcer, surrounded by an erythematous halo Ulcers may be necrotic or severely erosive 114 Chancroid: Diagnosis Probable diagnosis is usually a matter of exclusion Involves genitalia and unilateral bubo (or both) Painful genital ulcers in absence of T. pallidum and HSV (by inspection or culture) with coexisting tender inguinal lymphadenopathy is suggestive of chancroid Definitive diagnosis of chancroid is made morphologically, though the sensitivity of the test is no greater than 80% 115 116 117 9.3.42 Chancroid: Treatment Azithromycin (Zithromax) 1 gm p.o. x 1 dose OR Ceftriaxone (Rocephin) 250 mg IM x 1 dose OR Ciprofloxacin (Cipro) 500 mg p.o. BID x 3 days OR Erythromycin 500 mg p.o. QID x 7 days HIV + patients need a longer course of therapy Lymphogranuloma Venereum (LGV) Cause: Immunotypes L1, L2 or L3 of Chlamydia trachomatis Prevalence: Endemic in Asia, Africa and large cities in the United States 118 LGV: Symptoms 2 to 3 mm painless vesicle, bubo or non-indurated ulcer Regional adenopathy follows in approximately one month Stiffness and aching in groin followed by unilateral swelling of inguinal region 119 Lymphogranuloma Venereum 120 LGV Diagnosis: 121 May be confused with chancroid Definitive diagnosis requires isolating C. trachomatis from an appropriate specimen and confirming isolate as an LGV immunotype LGV Treatment: Doxycycline 100 mg p.o. BID x 21 days Erythromycin 500 mg p.o. QID x 21 days Aspirate buboes to prevent ulcerations 122 123 www.NPcourses.com 124 ~ THANK YOU ~ P.O. Box 69901 West Hollywood, CA 90069 310.684.3880 www.NPcourses.com 9.3.42