MKSAP Question

A 52-year-old man is evaluated for a 3-month history of perineal and suprapubic pain. He has experienced urinary frequency and dysuria for 4 to 6 weeks. The patient reports fatigue, insomnia, and low mood for the past 6 months. He has hypertension. Current medications are hydrochlorothiazide and acetaminophen as needed for pain.

On physical examination, temperature is normal, blood pressure is 138/80 mm Hg, and pulse rate is 78/min. BMI is 29. Abdominal examination is normal with mild suprapubic tenderness. The prostate is not enlarged; it is mildly tender without nodularity. Testicular examination is normal.
On laboratory study, urinalysis is normal, and urine culture is negative. Prostate-specific antigen level is 0.8 ng/mL (0.8 µg/L).

Which of the following is the most appropriate treatment for this patient?
A) Levofloxacin
B) Naproxen
C) Oxybutynin
D) Saw palmetto
E) Terazosin

See first comment for answer & explanation.

Identify the Image

What's the diagnosis?

This one's a softball, but good to see it to remind yourself what it looks like.  For a refresher on what a normal lateral neck film looks like, click here.

Answer in the first comment.
Reference: http://www.nejm.org/doi/full/10.1056/NEJMicm1009990

Primary Care for Childhood Survivors of Leukemia

Transition topic.  Fantastic NEJM article outlining primary care for childhood survivors of leukemia.
http://www.nejm.org/doi/full/10.1056/NEJMcp1103645?query=featured_home


Key Points:

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and 5-year survival rates in the United States have exceeded 70% for over two decades.

Adult survivors of childhood leukemia have increased risks of secondary cancers, cardiovascular disease, and other chronic illnesses, largely secondary to therapies for childhood cancer.

Clinicians caring for adult survivors of childhood leukemia should

• Request a treatment summary from the treating oncologist, a pediatric oncology program, or a local “survivor clinic.”

• Be aware that adults who received cranial radiotherapy as a component of treatment have increased risks of secondary tumors, stroke, growth hormone deficiency, and neurocognitive deficits.

• Check BMI, blood pressure, and lipids, since survivors of ALL have increased risks of obesity and associated metabolic derangements.

• Consider bone-density testing, since peak bone density is often reduced after childhood exposure to high-dose glucocorticoids and other therapies.

• Screen for left ventricular dysfunction in survivors who received anthracycline therapy, particularly if there was a high cumulative dose or treatment was before the age of 5 years.

Identify the Image

Just based on this image alone, what's the diagnosis in this 6 year old boy?

(answer in the first comment)

Breast Cancer Screening Guidelines

Given the data from randomized trials, which consistently show a 14 to 32% reduction in mortality from breast cancer with annual or biennial mammography in women 50 to 69 years of age, screening mammography should be recommended for women in this age group provided that their life expectancy is 5 years or more. For women 70 years of age or older, data from randomized trials are lacking, and the decision about screening should therefore be individualized on the basis of life expectancy and the patient's preference.

As for women in their 40s, there's not great consensus, and the decision should be individualized, with the recognition that the probability of a benefit is greater for women at higher risk.  For a woman in her 40s without risk factors, her chance of having invasive breast cancer over the next 8 years is about 1 in 80, and her chance of dying from it is about 1 in 400.

Mammographic screening every 2 years will detect two out of three cancers in women in their 40s and will reduce the risk of death from breast cancer by 15%. However, there is about a 40% chance that she will be called back for further imaging tests and a 3% chance that she will undergo biopsy, with a benign finding. Lifestyle modifications (e.g., weight control and avoidance of excessive alcohol consumption) that might lower her risk should also be discussed.

Reference: http://www.nejm.org/doi/full/10.1056/NEJMcp1101540

Case: Neck Swelling in an Adolescent

A previously healthy 13-year-old girl presents to the emergency department with a 2-week history of worsening sore throat and a 4-day history of left neck swelling, pain, and fever. Results of evaluation by a prior clinician at the onset of symptoms included a negative rapid streptococcal antigen test and a positive heterophile antibody test, prompting treatment with oral corticosteroids for 5 days as an anti-inflammatory medication. The girl now reports pain with swallowing, decreased oral intake, and left-sided head tilt for the past 24 hours.

On physical examination, the girl has a temperature of 38.4°C and appears to be in no acute distress. In addition, her heart rate is 91 beats/min, respiratory rate is 20 breaths/min, and blood pressure is 119/69 mm Hg. She has a warm, very tender, firm, anterior, left-sided 1.5-cm mass at the level of the thyroid gland. The mass moves when she swallows. Findings on the rest of her physical examination are normal.

Laboratory investigation reveals a white blood cell count of 17.2×10³/μL (17.2×10⁹/L) with 74% neutrophils and 14% lymphocytes, hemoglobin of 13 g/dL (130 g/L), and platelet count of 423×10³/μL (423×10⁹/L). C-reactive protein (CRP) measurement is elevated at 1.6 mg/dL (normal, 0.3 to 1.0 mg/dL). 

Images from a computed tomography (CT) scan of her neck with intravenous contrast enhancement are shown below.

What's the diagnosis?

***See first comment for answer.

MKSAP Question - Neurology

A 50-year-old man is evaluated for a 12-year history of slowly progressive left leg weakness and trouble ambulating. There is no history of transient neurologic symptoms. He has a history of hypertension, coronary artery disease, and chronic low back pain. Current medications are sublingual nitroglycerin, atenolol, aspirin, and occasional NSAIDs.

On physical examination, vital signs are normal. The patient has moderately severe spastic paraparesis that is worse on the left, with prominent circumduction of the left leg during ambulation. He requires a cane to ambulate 100 meters.

Cerebrospinal fluid analysis reveals the presence of oligoclonal bands.  MRIs of the brain and spine show lesions consistent with chronic multiple sclerosis.

Which of the following is the most appropriate treatment for this patient?

A) Glatiramer acetate

B) Interferon beta-1a

C) Natalizumab

D) Physical therapy


See first comment for correct answer with explanation.

UTI in Febrile Infants: Updated AAP Guidelines

A revised AAP clinical practice guideline on the diagnosis and management of the initial urinary tract infection (UTI) in febrile infants and young children is markedly different from the previous practice parameter published in 1999.  New data have become available in the past five years, with the findings prompting a reexamination of the older studies.  The notable changes are highlighted below:

1. Diagnosis: The criteria for diagnosis now include an abnormal urinalysis as well as a positive culture containing ≥ 50,000 colony forming units/milliliter of a urinary pathogen. The abnormal urinalysis helps distinguish true UTI from asymptomatic bacteriuria. Guidance also is provided regarding assessment of the likelihood of UTI to help determine which febrile infants clinicians should evaluate for UTI.
2. Treatment: Oral therapy is recognized as effective as parenteral therapy.
3. Imaging: Renal-bladder ultrasonography (RBUS) should be performed, but voiding cystourethrography (VCUG) no longer is recommended routinely after the first febrile UTI. Indications for VCUG include findings on RBUS that suggest the presence of high grade vesicoureteral reflux or the recurrence of a febrile UTI.
4. Follow-up: Emphasis should be on counseling families to seek medical evaluation promptly for UTI during future febrile illnesses.

The rationale for the biggest change — discouraging the routine performance of VCUGs — stems from analysis of the six recent randomized controlled trials of prophylaxis vs. no prophylaxis in young infants following a febrile UTI.

Prophylaxis was not demonstrated to be superior to no prophylaxis in preventing recurrence of febrile UTI in infants without reflux or in those with grades I-IV reflux. (In the studies, only five infants with grade V reflux were included, so the effectiveness of prophylaxis for infants with this grade of reflux is not known, but less than 1% of febrile infants with UTI have grade V reflux.)

Recurrent febrile UTI is less common among infants without high grade reflux, so waiting for the second UTI reduces the number of VCUGs performed by 90% and has a higher yield of infants with grades IV and V reflux. Studies of renal scarring suggest that waiting for the second UTI is acceptable and does not offset the benefit of sparing 90% of febrile infants with UTI the radiation, discomfort and cost of VCUG.

The figures in this updated guideline are worth scanning, including factors influencing the likelihood of UTI in febrile male & female infants; choices for parenteral and oral treatment of UTIs; sensitivity & specificity of diagnostic tests for UTI in infants; and a clinical practice guideline algorithm.

Reference: http://pediatrics.aappublications.org/content/128/3/595

Antihypertensive Choices

Thanks to Rita for this post, based on a recent encounter with a difficult to control hypertensive clinic patient:

He was already on Lopressor 100mg BID, Amlodipine 10mg daily, HCTZ 25mg daily combined with an ARB at maximum dose, and hydralazine 100mg TID.  He is at very high risk as he has already had a hemorrhagic stroke.  He also notes morning HTN.  

Reviewing Up to Date, we reminded ourselves a few things:

• Chlorthalidone is a better choice for a thiazide diuretic as it is likely a more potent anti-hypertensive agent, is definitely longer acting, and was the thiazide diuretic used in the ALLHAT study that showed thiazide superior to all other agents in preventing events.  It is very helpful for AM hypertension as the HCTZ likely has already worn off.  There is a more potent hypokalemic effect with chlorthalidone then HCTZ so monitoring is important as is with all diuretics
• The ACCOMPLISH study showed that for combination therapy, Amlodipine/ Benazepril was superior to other agents in preventing events and specifically was superior to Benazepril/ HCTZ which showed increased event rates.  The Up To Date authors actually recommend switching patients well controlled on ACE/ HCTZ to Amlodipine/ Benazepril. 
• Also our patient had cost issues with his ARB so was switched to a long acting ACE.
• In general young patients should be started on ACE or ARB’s as monotherapy with Bblocker as an alternative.  Of course remember in women of child bearing age to caution regarding ACE use.  Otherwise BBlockers should never be used as monotherapy.   Of course if there is a specific indication (post MI, CHF) B Blockers are indicated but would usually be combined with ACE-I.  There have been increased events in older patients with BBlockers.
• Older patients and African American patients should be given long acting CCB’s (like amlodipine) or thiazide diuretics (chlorthalidone preferred as above) as monotherapy
• Initial therapy of course also guided by comorbidities (DM or proteinuria:  ACE or ARB, Post MI, CHF, LV Dysfunction:  ACE-I/ BBlockers, etc.)

Note: Click link for great summary (in physician reference card form) of JNC 7 hypertension guidelines. And since I know you're all waiting with baited breath for it, JNC 8 is due out in 2012!  Mark your calendars!  --sds

Identify the Image

An 8-year-old boy was referred for evaluation of a mass in the midline of the ventral surface of the anterior tongue. The lesion had fluctuated in size since it was first noted 4 months earlier. He was otherwise asymptomatic, and his medical history revealed that he habitually bit his tongue. Examination of the tongue revealed a nontender, smooth-walled, translucent, bluish, fluctuant mass of approximately 8 mm in diameter that was resting on an opalescent base.


What's the diagnosis?
[see first comment to reveal answer]

Oral Diabetes Agents

Class	Mechanism of Action	Benefits	Risks/Concerns
Sulfonylureas	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; long duration of action	Extensive clinical experience; improved microvascular outcomes in UKPDS; low cost; once-daily dosing possible	Hypoglycemia; weight gain; potential impairment of cardiac ischemic preconditioning
Glyburide Glipizide Glimepiride
Glinides (meglitinides)	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; short duration of action	Target postprandial glucose; mimics physiologic insulin secretion	Hypoglycemia; weight gain; no long-term studies; expensive; frequent dosing (compliance an issue)
Repaglinide Nateglinide
Biguanides	Decrease hepatic glucose production	Extensive clinical experience; no hypoglycemia; weight loss or weight neutral; lipid and other nonglycemic vascular benefits; improved macrovascular outcomes; low cost; once-daily dosing available (sustained-release product)	Diarrhea, abdominal discomfort; many contraindications to consider, including serum creatinine >1.4 mg/dL (123.76 µmol/L) and lactic acidosis risk (rare); lowers vitamin B12 levels (without apparent effects on hematologic indices or neurologic function)
Metformin
α-Glucosidase inhibitors	Retard gut carbohydrate absorption	Target postprandial glucose; weight-neutral; nonsystemic	Flatulence, abdominal discomfort; frequent dosing (compliance); expensive
Acarbose Miglitol
Thiazolidinediones	Activate the nuclear receptor PPARγ, increasing peripheral insulin sensitivity. May also reduce hepatic glucose production	Address primary defect of T2DM; no hypoglycemia; lipid and other nonglycemic vascular benefits; probable decreased macrovascular outcomes with pioglitazone; greater durability of effectiveness; once-daily dosing	Edema and heart failure risk; weight gain; possible increased fracture risk in women; possible increased myocardial infarction risk with rosiglitazone; slow onset of action; expensive
Rosiglitazone Pioglitazone
Amylinomimetics	Activate amylin receptors, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	Weight loss	Nausea, vomiting; hypoglycemia risk when used with insulin; no long-term studies; injectable; expensive; frequent dosing (compliance)
Pramlintide
Incretin modulators	Activate GLP-1 receptors, increasing glucose-dependent insulin secretion, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	No hypoglycemia; weight loss	Nausea, vomiting; possible pancreatitis (rare); no long-term studies; injectable; expensive
GLP-1 mimetics Exenatide
DPP-IV inhibitors	Inhibit degradation of endogenous GLP-1 and GIP, thereby enhancing the effect of these incretins on insulin and glucagon secretion	No hypoglycemia; weight neutral; once-daily dosing	Possible urticaria/angioedema (rare); no long-term studies; expensive
Sitagliptin
Bile acid sequestrants	Bind cholesterol within bile acid; unknown mechanisms of antihyperglycemic effect	No hypoglycemia; weight neutral; lowers LDL-cholesterol	Constipation; may increase triglycerides; no long-term studies; expensive
Colesevelam

Reference: MKSAP 15
http://mksap15.acponline.org/tables/en_t07

Hyperbilirubinemia in the Newborn

Excellent, concise summary of hyperbilirubinemia in the newborn from Pediatrics in Review.

Link to full text of PIR article.

Remember: http://bilitool.org/

 Summary

• Based on strong research evidence, breastfeeding, prematurity, significant jaundice in a previous sibling, and jaundice noted before discharge from the nursery are the most common risk factors associated with severe hyperbilirubinemia.
• Based on research evaluating benefit versus harm, jaundice in the first 24 hours after birth is not physiologic jaundice and needs further evaluation.
• All newborns should undergo a risk assessment for hyperbilirubinemia before discharge from the newborn nursery and have appropriate follow-up evaluation after discharge.
• Visual assessment of jaundice does not assess the TSB reliably; clinicians should check either a TSB or TcB when in doubt.
• The infant's age in hours is used when evaluating and managing bilirubin concentrations.

Fixed Drug Eruption

A 35-year-old man presented with a 10-day history of a cutaneous lesion on the left anterior chest. Examination revealed an annular, scaly, blistering, violaceous plaque, 5 cm in diameter, with an erythematous periphery. The lesion had appeared 24 hours after the patient began a self-prescribed course of oral trimethoprim–sulfamethoxazole for a respiratory tract infection. Six months earlier, an identical lesion had appeared in the same location after the patient had taken the same drug for 3 days. This first lesion healed after 3 weeks, but residual hyperpigmentation remained. On the basis of this characteristic presentation, a diagnosis of fixed drug eruption was made. Fixed drug eruptions are common, immune-mediated, cutaneous lesions that are typically of acute onset and appear as annular, edematous, sometimes blistering, reddish-brown to violaceous macules or plaques. Their diagnostic hallmarks include residual hyperpigmentation after healing and recurrence at previously affected sites, with subsequent antigenic challenges. This patient received a prescription for a 3-week course of topical glucocorticoids and was advised to avoid sulfonamides in the future.

Reference:

http://www.nejm.org/doi/full/10.1056/NEJMicm1013871

Cutaneous Warts

A 56-year-old man with type 2 diabetes mellitus presented with a 2-year history of slowly progressing, painless lesions on his fingertips. Physical examination revealed hyperkeratotic papules that were clinically diagnostic of common warts (Panels A and B). Warts are a manifestation of cutaneous infection with human papillomavirus (HPV). To limit the cost of the medical supplies required for fingerstick capillary blood glucose monitoring, the patient had been reusing the same lancet several times per day. Cycling from finger to finger resulted in the sequential inoculation of each fingertip with HPV. The patient was advised not to reuse the skin-prick lancets. After 6 weeks of topical treatment with fluorouracil and salicylic acid preparations, there was substantial improvement in the appearance of the lesions (Panel C).

Reference:
http://www.nejm.org/doi/full/10.1056/NEJMicm1009053