Internal Medicine
Summer Board Review
General Internal Medicine
Session 3
Mashkur Husain
Question 25
A
25-year-old woman is evaluated for a 1-week history of
malodorous vaginal discharge associated with vulvar itching and
burning. She is sexually active and has had three partners in the past 6
months. She has no history of sexually transmitted infection.
On
physical examination, vital signs are normal. BMI is 22. There is a
thin, gray, homogeneous discharge coating the vaginal walls. There are
no external genital lesions and no vulvar erythema or excoriations.
The cervix appears normal.There is no cervical motion tenderness or
adnexal tenderness.Vaginal pH is 6.0, “whiff” test is positive. Results of
saline microscopy are shown (next slide) Microscopy after the
addition of potassium hydroxide does not show hyphae or
pseudohyphae. A urine pregnancy test is negative.
Answer Choice
Which of the following is the most appropriate treatment?
A
Clotrimazole cream, 7-day topical regimen
B
Fluconazole, single-dose oral regimen
C
Metronidazole, 7-day oral regimen
D
Metronidazole, single-dose oral regimen
Answer Choice
Which of the following is the most appropriate treatment?
A
Clotrimazole cream, 7-day topical regimen
B
Fluconazole, single-dose oral regimen
C
Metronidazole, 7-day oral regimen
D
Metronidazole, single-dose oral regimen
Key Point and Education Objective

Treat bacterial vaginosis

Bacterial vaginosis is the likely diagnosis in
women with at least three of the following
features: (1) homogeneous thin discharge that
coats the vaginal walls; (2) clue cells on saline
microscopy; (3) pH of vaginal fluid >4.5; and (4)
fishy odor of vaginal discharge (positive “whiff”
test).
Explanation

The most appropriate treatment for this patient is a 7-day oral regimen of
metronidazole (500 mg twice daily). She has bacterial vaginosis (BV), a polymicrobial
infection characterized by an overgrowth of multiple anaerobic bacteria. Although
BV is not a sexually transmitted infection, risk factors include lack of condom use
and multiple or new sexual partners. BV can be diagnosed clinically using Amsel
criteria, which include the following symptoms or signs: (1) homogeneous thin
discharge that coats the vaginal walls; (2) clue cells (epithelial cells with borders
obscured by small bacteria) on saline microscopy; (3) pH of vaginal fluid >4.5; and
(4) fishy odor of vaginal discharge before or after the addition of 10% potassium
hydroxide to the secretions (the “whiff” test). The presence of at least three of
these clinical findings has a high sensitivity and specificity for diagnosing BV when
compared with Gram stain of collected secretions, which is the gold standard.
Because this woman is symptomatic, treatment should be offered with either oral
metronidazole, vaginal metronidazole gel, or vaginal clindamycin cream; patient
preference should dictate treatment choice. Topical clindamycin should be avoided
during pregnancy as it may increase the risk of adverse outcomes. Women treated
with oral metronidazole should be cautioned to avoid alcohol, which can cause a
disulfiram-like reaction.
Explanation

This patient's abnormal vaginal pH and lack of yeast and hyphae on potassium
hydroxide preparation make vulvovaginal candidiasis an unlikely explanation for her
symptoms. Treatment with oral fluconazole or topical clotrimazole cream, effective
therapies for vulvovaginal candidiasis, is not warranted.

This patient has multiple sexual partners, increasing her risk for trichomoniasis.
Characteristic symptoms and signs include a malodorous discharge with vulvar
itching, burning, and postcoital bleeding. Although the vaginal pH will be elevated and
the whiff test may be positive (as noted with this patient), clue cells are not a
characteristic finding on saline microscopy, making trichomoniasis an unlikely
diagnosis in this patient.

Oral metronidazole is also used for the treatment of trichomoniasis, but it is
typically given as a single 2-g dose, which would not be appropriate for treatment of
BV.
Vaginitis and Cervicitis
Screening
Screen all sexually active women age ≤25 years and all women age
>25 years with risk factors for Chlamydia infection.
Diagnosis
Vaginitis is characterized by vaginal irritation, pruritus, pain, or unusual
discharge. The three most common infectious causes of acute vaginitis
are bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas.
Trichomoniasis is the only cause of vaginitis that is sexually
transmitted. Noninfectious causes include allergic reactions to vaginal
contraceptives or other products, such as douches, tampons, or soap;
coitus-induced friction; or postmenopausal atrophy.
Vaginitis and Cervicitis
Cervicitis may be asymptomatic or symptomatic. When present,
symptoms include vaginal discharge, postcoital bleeding, dysuria, and
dyspareunia. The presence of endocervical mucopus defines cervicitis.
Easily induced endocervical bleeding also may occur. Cervical motion
tenderness suggests pelvic inflammatory disease. Cervicitis can be
caused by Chlamydia, Neisseria gonorrhoeae, and Trichomonas.
Definitive diagnosis of Neisseria and Chlamydia can be made by
nucleic acid amplification test performed on vaginal or urine
specimens.
Vaginitis and Cervicitis
Candida Albicans
Clue Cell
Vaginitis and Cervicitis
Question 26
A
28-year-old woman is evaluated for a painful lump in her left breast
of 6 weeks' duration. There is neither discharge from the nipple nor
skin changes over the area. Her last normal menstrual period was 3
weeks ago and she thinks that the lump became slightly larger right
before and during her menses. She is on low-dose oral contraceptives.
She has no history of breast disease or breast biopsy. Menarche was at
age 12 years. She has never been pregnant. A maternal aunt had breast
cancer.
On
physical examination, vital signs are normal. BMI is 24. There is a
1.5-cm mobile, soft, slightly tender mass in the lower medial quadrant
of the left breast. There is no nipple discharge and no abnormalities of
the overlying skin. The right breast has no masses. There is no axillary
lymphadenopathy. The remainder of the examination is unremarkable.
Answer Choice
Which of the following is the most
appropriate management of this patient?
A
B
C
D
Core needle biopsy
Mammography
Repeat clinical breast examination
in 6 months
Ultrasonography
Answer Choice
Which of the following is the most
appropriate management of this patient?
A
B
C
D
Core needle biopsy
Mammography
Repeat clinical breast examination in 6
months
Ultrasonography
Key Point and Education Objective
Evaluate a breast mass in a young woman.
 A palpable breast mass should be
evaluated until diagnosis or resolution

Explanation

This patient should undergo ultrasonography. A slightly tender,
discrete, round, soft, and mobile breast mass, with no nipple
discharge and no overlying skin changes, is consistent with a
fibroadenoma or benign cyst and not breast cancer. However, no
single clinical factor by history or physical examination has
sufficient accuracy to rule in or rule out underlying malignancy, and
diagnostic imaging should be performed. Ultrasonography serves to
distinguish cystic from solid masses. A cystic mass should be
aspirated and the fluid sent for cytologic evaluation if bloody or
recurrent. A solid mass requires biopsy by fine-needle aspiration,
core needle, or excision. A benign biopsy in a woman with a normal
mammogram still requires close follow-up, as documented by a
study in which breast cancer developed in 707 of 9087 women
with previous benign breast biopsies followed for a median of 15
years.
Explanation

In general, imaging should precede core needle biopsy. A core
needle biopsy will not be necessary if the mass is definitively cystic
by ultrasonography.

The increased density of breast tissue in women 30 to 35 years of
age and younger may limit the utility of mammography, making
ultrasonography a better first choice. Ultrasonography can readily
distinguish cystic from solid lesions and guide further evaluation,
such as aspiration, if needed.

Clinical observation and follow-up in 6 months is not appropriate
for a palpable breast mass, which should be evaluated until
diagnosis or resolution.
Breast Lump
Diagnosis
A dominant breast mass is defined as a lump or suspicious
change in the breast texture that is discrete and distinctly
different from the rest of the surrounding breast tissue.
The differential diagnosis of a dominant breast mass
includes cysts, fibroadenomas, fibrocystic changes, fat
necrosis, carcinoma in situ, and invasive carcinoma.
Don't Be Tricked
Do not stop the evaluation of a breast mass if
mammogram is normal. Ultrasonography is followed by
aspiration of cysts or biopsy of solid breast masses
regardless of mammogram results.
Question 27
A
38-year-old woman is evaluated during a routine examination. She
has recently divorced and is interested in some form of hormonal
contraception, as her ex-husband had a vasectomy after their last
child, and she does not want to use condoms. She has no history of
deep venous thrombosis, hypertension, or heart disease. She drinks
one glass of wine 4 or 5 nights per week, and smokes a pack of
cigarettes daily. Family history is significant for stroke in her mother at
age 72 years. All previous Pap smears have been negative.
Physical
examination, including pelvic examination, is normal. A Pap
smear is obtained.
Answer Choice
Which of the following is the most
appropriate hormonal contraceptive option
for this patient?
A
B
C
D
Estrogen patch
Estrogen-progesterone
combination
Progesterone contraceptive
No hormonal-based method
Answer Choice
Which of the following is the most
appropriate hormonal contraceptive option
for this patient?
A
B
C
D
Estrogen patch
Estrogen-progesterone combination
Progesterone contraceptive
No hormonal-based method
Key Point and Education Objective

Recommend contraception options for a
woman who smokes.

Estrogen-containing contraceptives are
contraindicated in women older than 35
years who smoke more than 15 cigarettes
daily because of the increased risk of
thromboembolic disease.
Explanation

The best hormonal contraception option for this 38-year-old woman who smokes is
a progesterone-only preparation. Women older than 35 years who smoke more
than 15 cigarettes daily should not be prescribed estrogen-containing preparations
because of the increased risk of thromboembolic disease. A family history of stroke
itself is not a contraindication to the use of estrogen-containing preparations,
although a personal history of stroke or thromboembolic disease is; progesteroneonly contraceptives are considered safe in these women. Progesterone-only options
for women with contraindications to estrogen include the “mini-pill,” long-acting
progesterone compounds (such as depot medroxyprogesterone acetate),
subcutaneous progesterone implants, and progesterone-containing intrauterine
devices.

Estrogen-only patches are never appropriate for contraception; they may be used as
hormone replacement therapy in postmenopausal women without an intact uterus.

Combined estrogen-progesterone preparations are available in the form of patches
and vaginal rings, which avoid first-pass hepatic metabolism and may limit estrogen's
effects on the liver and on lipids. These products do not negate the thrombogenic
effects of estrogen, however, and so they are still contraindicated in women who
smoke.
Contraception
Key Considerations
 The combination estrogen-progestin OCPs, containing ethinyl
estradiol and one of various progestins, are very effective. Use is
associated with reduced risks of ovarian cancer and endometrial
cancer. Users experience less acne and reduced severity of
abnormal uterine bleeding, menstrual blood flow, and anemia.
 The risk for VTE is higher in patients who smoke and have
thrombophilia, although routine screening for thrombophilia is not
recommended. The risks for MI and ischemic stroke are higher in
patients with diabetes or hypercholesterolemia. Breast cancer risk
is controversial. OCPs are safe in nonsmoking women older than
the age of 35 years until menopause.
Contraception


Other hormonal contraceptives include the topical patch, vaginal
ring, progestin-only pill, and medroxyprogesterone acetate injection.
A single-rod progestin implant is now available in the United States
that provides contraception for 3 years. Progesterone-only
contraceptives are alternatives for women who cannot take
estrogen because of breastfeeding or estrogen side effects.
Two types of pills are available for emergency contraception. Both
must be taken within 5 days of a risked pregnancy. Levonorgestrel is
the preferred formulation because it is more efficacious and has the
fewest side effects. The second option is a combination of ethinyl
estradiol and levonorgestrel.
Nonhormonal Contraceptives
Question 27
A
61-year-old woman is evaluated for hot flushes, which have been
persistent for the last 10 years. They occur at least 7 times per day,
last for approximately 60 seconds, and are associated with severe
sweating, palpitations, and occasional nausea. She is awakened several
times per night. She has tried herbal medications, including soy and
black cohosh, but has not experienced any benefit. She has
hypertension, type 2 diabetes mellitus, and hyperlipidemia. Five years
ago, she developed deep venous thrombosis after hip replacement
surgery. Her current medications are ramipril, metformin, atorvastatin,
calcium, and vitamin D.
On
physical examination, vital signs are normal. BMI is 29. The
remainder of the examination is normal
Answer Choice
Which of the following is the most
appropriate treatment?
A
B
C
D
E
Citalopram
Oral estrogen therapy
Oral estrogen/progesterone
therapy
Topical (vaginal) estrogen
Venlafaxine
Answer Choice
Which of the following is the most
appropriate treatment?
A
B
C
D
E
Citalopram
Oral estrogen therapy
Oral estrogen/progesterone
therapy
Topical (vaginal) estrogen
Venlafaxine
Key Point and Education Objective

Treat menopausal vasomotor symptoms

Owing to cardiovascular and thromboembolic
risks, systemic hormone therapy is not
recommended for treatment of menopausal
vasomotor symptoms in women older than 60
years who experienced menopause at the
median age
Explanation

This 61-year-old woman with cardiovascular risk factors and a history of
deep venous thrombosis should be started on a nonhormonal therapy for
her hot flushes. Certain antidepressants, including serotoninnorepinephrine reuptake inhibitors such as venlafaxine, are effective
nonhormonal medications for reducing menopausal vasomotor symptoms.

Approximately 10% of menopausal women experience hot flushes for 7 to
10 years after the cessation of menses. This patient is continuing to
experience frequent and severe hot flushes which have been refractory to
conservative therapy and are decreasing her quality of life; thus,
pharmacologic therapy is warranted. Systemic estrogen therapy is the most
effective treatment for the relief of menopausal hot flushes and must be
coadministered with progesterone in women with an intact uterus.
However, combined estrogen and progesterone therapy has been shown to
increase the risk of several adverse outcomes, including coronary heart
disease, stroke, invasive breast cancer, and venous thromboembolism.

The North American Menopause Society guideline notes that women older than 60
years who experienced natural menopause at the median age and have never used
hormone therapy will have elevated baseline risks of cardiovascular disease, venous
thromboembolism, and breast cancer; hormone therapy, therefore, should not be
initiated in this population without a compelling indication and only after
appropriate counseling and attention to cardiovascular risk factors. Moreover, this
patient has a history of deep venous thrombosis, which is an absolute
contraindication to initiating hormone therapy.

Several nonhormonal medications have been found to be effective for the treatment
of menopausal hot flushes. Notably, there is a significant placebo effect: in most
studies, approximately one-third of women will experience relief of hot flushes, even
if they do not receive active treatment. In numerous studies, venlafaxine,
administered at doses of 37.5 mg/d to 150 mg/d, decreases hot flush severity and
frequency in approximately 60% of patients (as compared with 30% who
experienced benefit with placebo treatment). Paroxetine is similarly beneficial; in
contrast, few studies have shown efficacy with fluoxetine or citalopram. Gabapentin
and clonidine are two additional nonhormonal treatments that reduce hot flushes,
but attendant side effects may limit their use in some patients.

Vaginal estrogen therapy is typically used for the isolated treatment of vaginal
dryness, pruritus, and dyspareunia. Treatment with vaginal estrogen tablets will
improve local vaginal symptoms, but will not improve menopausal vasomotor
symptoms.
Menopause
Diagnosis
When menstruation ceases, an FSH level >30 milliunits/mL is
considered diagnostic of menopause, but this finding is not usually
needed for diagnosis. Perimenopause is marked by menstrual cycle
irregularity, but approximately 30% of women experience the
hallmarks of menopause, hot flushes and night sweats, before
menstrual changes. Estrogen deficiency can lead to dyspareunia,
atrophic vaginitis, dysuria, urgency, and frequency. Menopause is
defined as the time following 12 months of amenorrhea.
Vaginal epithelial cells contain less glycogen, resulting in increased
vaginal pH and increased growth of Escherichia coli. Loss of lactobacilli
leaves this pale, thin, friable tissue vulnerable to infection and
ulceration.
Menopause
Therapy
Vaginal
moisturizers or lubricants are indicated for urogenital atrophy.
Exercise and cessation of cigarette smoking may relieve menopausal
symptoms. Use short-term hormone replacement therapy (2 to 3 years) only
for patients with intolerable vasomotor symptoms. Gabapentin, serotoninnorepinephrine reuptake inhibitors (SNRIs), or SSRIs are alternatives for
reducing hot flushes. Local (topical) estrogen helps relieve dyspareunia and
vaginal dryness.
Don't Be Tricked
Do
not prescribe hormone replacement therapy for prevention or relief of
urinary incontinence, decreased libido, or cardiovascular risk, which could
even increase with this therapy.
Do
not select phytoestrogens and black cohosh for the treatment of
menopausal symptoms. They are no more effective than placebo.
Question 28
A
42-year-old woman is evaluated for a 6-month history of heavy
menstrual bleeding. She has been menstruating for the last 8 days and
is still going through 10 pads or more daily with frequent clots. She
has fatigue but no dizziness. Previous evaluation for this problem has
included normal thyroid function and prolactin testing. She has no
other medical problems and takes no medications. Pelvic
ultrasonography has demonstrated a large posterior submucosal
fibroid. A surgical treatment is planned in 2 weeks.
On
physical examination, vital signs are normal. Abdominal
examination is benign, and the pelvic examination reveals a moderate
amount of blood in the vaginal vault.
Hemoglobin
level is 10.5 g/dL (105 g/L). Pregnancy test is negative.
Answer Choice
Which of the following is the most
appropriate next management step?
A
B
C
D
Estrogen/progesterone multiphasic
oral contraceptive
Intravenous estrogen
Oral medroxyprogesterone acetate
Reevaluation in 1 week
Answer Choice
Which of the following is the most
appropriate next management step?
A
B
C
D
Estrogen/progesterone multiphasic
oral contraceptive
Intravenous estrogen
Oral medroxyprogesterone acetate
Reevaluation in 1 week
Key Point and Education Objective
Treat heavy menstrual bleeding
 Medroxyprogesterone acetate for 10 to
21 days is effective treatment for
moderate menstrual bleeding.

Explanation

The most appropriate next management step is oral medroxyprogesterone acetate.
In patients who present with menorrhagia (heavy menstrual bleeding) with a known
etiology, several therapeutic agents can decrease bleeding. For moderate bleeding
that can be managed on an outpatient basis, a progestational agent such as
medroxyprogesterone acetate can be given for 10 to 21 days. The progesterone will
typically act to stabilize the endometrium and stop uterine blood flow.

Estrogen/progesterone-containing oral contraceptives may be useful in decreasing
menstrual blood loss, although the doses of both agents in most typical formulations
would likely be inadequate to control the degree of bleeding in this patient,
particularly with a multiphasic preparation. If a specific progestational agent is not
available, a monophasic oral contraceptive may be dosed four times daily for 5 to 7
days, and subsequently reduced to daily dosing until definitive treatment is
undertaken.

If the patient were orthostatic or dizzy from blood loss, intravenous estrogen would
be appropriate. Parenteral conjugated estrogens are approximately 70% effective in
stopping the bleeding entirely. Pulmonary embolism and venous thrombosis are
complications of intravenous estrogen therapy.

Monitoring the patient for an additional week of observation is not appropriate
given her significant, ongoing blood loss.
Abnormal Uterine Bleeding
Question 29
A
19-year-old woman is evaluated for painful menses. She usually
misses one or two days of school each month owing to these
symptoms, which include cramps and nausea. Menarche occurred at
age 12 years. Menses have been regular for the past 2 years, occurring
every 29 days. The patient is not sexually active, and her medical
history is noncontributory. She takes no medications.
Physical
examination, including external pelvic examination, is normal.
Answer Choice
Which of the following is the most appropriate
management option for this patient?
A
B
C
D
E
Combined estrogen-progesterone
contraceptive
Depot medroxyprogesterone acetate
Ibuprofen
Measurement of follicle-stimulating
hormone and luteinizing hormone levels
Pelvic ultrasound
Answer Choice
Which of the following is the most appropriate
management option for this patient?
A
B
C
D
E
Combined estrogen-progesterone
contraceptive
Depot medroxyprogesterone acetate
Ibuprofen
Measurement of follicle-stimulating
hormone and luteinizing hormone levels
Pelvic ultrasound
Key Point and Education Objective

Manage primary dysmenorrhea

The first-line treatment for primary
dysmenorrhea is NSAID therapy.
Explanation

The most appropriate management option for this patient is a trial
of NSAID therapy, such as ibuprofen. This patient has
dysmenorrhea associated with normal menstrual cycles and no
pelvic pathology. Initial treatment options for primary
dysmenorrhea include NSAIDs and cyclooxygenase-2 inhibitors,
which inhibit the inflammation, vasoconstriction, and uterine
ischemia that are thought to cause the symptoms.

If symptoms are not relieved with NSAID therapy or the patient
requests contraception or is sexually active, a combination
estrogen-progesterone contraceptive would be appropriate.
Extended-cycle formulations are particularly useful for this
indication.
Explanation

Depot medroxyprogesterone acetate (DMPA) is a long-acting
progesterone compound, administered intramuscularly or subcutaneously
every 12 to 14 weeks. Long-acting progesterone therapy is a treatment
option for dysmenorrhea, and also provides contraception. For adolescents
and young adults, however, long-term use of progesterone therapy
decreases bone mineral density owing to prolonged estrogen deficiency.
Therefore, such treatment should be used with caution for dysmenorrhea
or for contraception in younger women based on the risks and benefits of
treatment in a given patient. In general, NSAIDs should be tried before
hormonal therapy.

In the absence of worrisome symptoms such as severe pelvic pain or
significant bleeding abnormalities, treatment for dysmenorrhea may be
initiated without further evaluation, such as pelvic imaging, hormonal
testing, or gynecologic referral.
Primary Dysmenorrhea
Diagnosis
Patients with a history of menstrual pain that begins within 1 to 2
years of menarche and sometimes worsens over time usually have
primary dysmenorrhea, in which no pathologic cause for the
menstrual pain exists. An underlying cause for dysmenorrhea is likely
in the setting of noncyclic pain, abnormal discharge, dyspareunia, or
heavy or irregular bleeding.
Therapy
NSAIDs are an effective first-line therapy. For women who are not
trying to conceive, oral contraceptive pills are also effective therapy, as
are transcutaneous electrical nerve stimulation and vitamin B1.
Question 30
A
33-year-old woman is evaluated for chronic lower pelvic pain. It
has been persistent for the past year but has worsened in recent
months. She describes it as a constant, aching discomfort centered
over her lower pelvis that persists during her menstrual cycle and has
prevented her from being sexually active with her partner. She also
reports a 4-month history of urinary urgency and frequency. She has
been empirically treated twice for urinary tract infections, but her
urinary symptoms improve for only a few days and then recur. She has
no history of pelvic surgeries or pelvic infections and has never been
pregnant. She has no associated constipation, diarrhea, abdominal
distention, or flank pain. She currently takes ibuprofen as needed for
pain.



On physical examination, vital signs are normal. BMI is 24. There is
mild tenderness to palpation over the pelvic floor muscles with
significant tenderness over the anterior vaginal wall. External
genitalia are normal in appearance; there is no tenderness to
palpation over the vulva. There is no cervical motion tenderness,
adnexal tenderness, or discomfort with palpation of the uterus
Laboratory studies show normal electrolytes, kidney function, and a
complete blood count. Erythrocyte sedimentation rate is 4 mm/h.
Urinalysis is without erythrocytes or leukocytes and is negative for
nitrite and leukocyte esterase. Urine culture is negative. Tests for
chlamydial infection and gonorrhea are negative.
Transvaginal/transabdominal ultrasonography is negative for
endometrial or ovarian masses and no abnormalities are noted.
Answer Choice
Which of the following is the most likely
diagnosis?
A
B
C
D
Endometriosis
Interstitial cystitis
Irritable bowel syndrome
Pelvic adhesions
Answer Choice
Which of the following is the most likely
diagnosis?
A
B
C
D
Endometriosis
Interstitial cystitis
Irritable bowel syndrome
Pelvic adhesions
Key Point and Education Objective

Diagnose interstitial cystitis as a cause of
chronic pelvic pain.

Interstitial cystitis is a likely diagnosis in
women with chronic pelvic pain
associated with unexplained urinary
symptoms; most women with interstitial
cystitis have been treated empirically
several times for urinary tract infections.
Explanation

This most likely diagnosis in this patient with chronic pelvic pain is
interstitial cystitis. Chronic pelvic pain is defined as noncyclic pain of at
least 6 months' duration that localizes to the anatomic pelvis, the anterior
abdominal wall at or below the umbilicus, the lumbosacral back, or the
buttocks, and is of sufficient severity to impair quality of life. Potential
causes of chronic pelvic pain include interstitial cystitis, endometriosis,
pelvic adhesions, and irritable bowel syndrome. In this patient, the
combination of chronic pelvic pain in association with unexplained urinary
symptoms is most consistent with a diagnosis of interstitial cystitis.
Interstitial cystitis is a chronic inflammatory condition of the bladder that
causes symptoms of urinary urgency, frequency, and pelvic discomfort. The
pelvic discomfort may be worsened by sexual intercourse, and patients
may urinate numerous times per day. Although urinalysis and urine cultures
are almost always negative, most women with interstitial cystitis have been
treated empirically several times for urinary tract infections.
Explanation

Endometriosis is a common cause of chronic pelvic pain, and patients
typically report severe dysmenorrhea, cyclic pain, and dyspareunia. The
absence of severe dysmenorrhea and the noncyclic nature of this patient's
pelvic pain make endometriosis a less likely diagnosis. Similarly, irritable
bowel syndrome is unlikely to explain her symptoms in the absence of any
associated gastrointestinal symptoms.

Adhesions are diagnosed in 25% to 50% of women with chronic pelvic
pain. Pelvic adhesions typically form in the setting of acute or chronic
inflammatory processes, such as infection, or surgery. This patient has no
history of pelvic infection and has never had pelvic surgery, making this an
unlikely cause of her symptoms.
Endometriosis
Endometriosis
Don't Be Tricked
Endometriosis does not cause fever or vaginal discharge.
Therapy
NSAIDs are first-line therapy, followed by oral contraceptives (if
pregnancy is not desired) when NSAIDs are ineffective. Severe
symptoms call for gonadotropin-releasing hormone agonists for pain
relief. Surgical ablation or resection of endometrial tissue is
recommended for patients who do not respond to conservative
measures. However, women with noncyclic pain, migratory pain, and
normal pelvic examinations are unlikely to benefit from surgery.
Counseling
syndrome.
is important for abused women with chronic pelvic pain
Question 31
A 69-year-old woman is evaluated for involuntary leakage of urine
with coughing, sneezing, laughing, or when lifting heavy boxes at work.
She has no dysuria, frequency, or urgency and she has no mobility
problems. She is gravida 4, para 4, and underwent a total abdominal
hysterectomy 20 years ago for uterine fibroids. She has type 2
diabetes mellitus. Medications are metformin and lisinopril. She has no
known drug allergies.
On physical examination, vital signs are normal. BMI is 31. There is
bulging of the anterior vaginal wall when the patient is asked to cough,
accompanied by leakage of urine. Bimanual examination is
unremarkable. The remainder of her examination is normal.
Laboratory studies show fasting plasma glucose level of 89 mg/dL (5.0
mmol/L) with hemoglobin A1c of 6.5%. Urinalysis is normal.
Answer Choice
Which of the following is the most appropriate
treatment?
A
B
C
D
Pelvic floor muscle training
Prompted voiding
Pubovaginal sling
Tolterodine
Answer Choice
Which of the following is the most appropriate
treatment?
A
B
C
D
Pelvic floor muscle training
Prompted voiding
Pubovaginal sling
Tolterodine
Key Point and Education Objective

Treat stress urinary incontinence

Pelvic floor muscle training is first-line
treatment for stress urinary incontinence.
Explanation

This patient has stress urinary incontinence and should receive pelvic floor
muscle training (PFMT). Stress urinary incontinence, defined as loss of
urine with physical activity, cough, or sneeze, is caused by sphincter
incompetence. Findings on physical examination include weakened anterior
or posterior vaginal wall support (cystocele or rectocele, respectively).
PFMT is considered first-line therapy for urinary stress incontinence. In
PFMT, women learn repetitive exercises (Kegel exercises) to strengthen
the voluntary urethral sphincter and levator ani muscles. For PFMT to be
effective, it is important that the patient learn to correctly contract her
muscles without straining, which increases abdominal pressure. Each
contraction is held for approximately 10 seconds, followed by an equal
relaxation period. The number of repetitions should be increased weekly
until the patient is performing 8 to 12 repetitions three times daily, every
day or at least 3 to 4 days per week. In a systematic review of nonsurgical
therapy, PFMT improved stress urinary incontinence episodes. Outcomes
were even better when PFMT was combined with biofeedback and when
skilled therapists directed the treatment.
Explanation

Prompted voiding is indicated in and is effective in patients with significant
mobility or cognitive impairments that may hinder the patient's ability to
reach the toilet in time, neither of which this patient has.

Sling procedures are effective for moderate to severe stress incontinence,
but surgery is usually reserved for patients who do not benefit from more
conservative approaches, including behavioral or appropriate
pharmacologic therapy.

Tolterodine, a selective antimuscarinic anticholinergic medication, is most
effective for patients with urge, rather than stress, incontinence. This
patient does not experience the classic sense of urinary urgency with her
incontinence episodes, and, therefore, tolterodine would not be an
appropriate first choice.
Urinary Incontinence
Urinary Incontinence
Therapy

Begin nondrug therapy in all patients with urinary incontinence regardless
of what other interventions may eventually be needed. Evaluate for other
reversible factors contributing to symptoms, such as diuretics or poorly
controlled diabetes.

Oxybutynin and tolterodine provide minor relief of urge incontinence but
are associated with side effects related to anticholinergic properties.

Stress incontinence cannot be treated with medications. Topical estrogen
helps women with stress incontinence and atrophic vaginitis. Pelvic floor
muscle training and biofeedback is also effective for stress incontinence.

Imipramine (not FDA approved for this indication) may offer some benefit
for combined urge and stress incontinence, although anticholinergic side
effects are a factor.

Prompted urination (asking about incontinence, reminding patient to use
the toilet, positive feedback for continence and toilet use) is effective for
functional incontinence (inability to get to the toilet because mental or
physical disability).
Don't Be Tricked

Do not prescribe systemic estrogen-progestin therapy because it can worsen stress
and urge incontinence.

Do not order urodynamic testing because outcomes are no better than those
associated with management based on clinical evaluation alone.
Test Yourself

A 78-year-old woman has urinary urgency, nocturia, and urine loss with coughing
and sneezing. Her medical history includes HF and glaucoma.

ANSWER: The diagnosis is combined stress and urge incontinence. Begin pelvic
muscle exercises and bladder training techniques. Imipramine is contraindicated
because of its anticholinergic effects.
Question 32
A
32-year-old woman presents for emergency department follow-up.
She was seen 1 week ago for a facial laceration. She tells you she
cannot remember the incident. She had a humeral fracture 1 year ago,
and has had bruising on her arms and legs on several visits. History is
significant for depression and recurrent urinary tract infection. Her
only current medication is citalopram. Upon questioning about
intimate partner violence, the patient admits that her husband often
beats her.
Physical
examination is significant for normal vital signs; a healing,
sutured, 4-cm laceration across the left zygomatic arch; and several 5to 6-cm ecchymoses on her upper extremities.
Answer Choice
Which of the following is the most appropriate
next step in management?
A
Advise the patient to leave her current
living situation immediately
B
Ask her to bring her husband to her next
appointment
C
Assess her immediate safety and
develop a safety plan
D
Report the husband to the police
E
Request psychiatry consultation
Answer Choice
Which of the following is the most appropriate
next step in management?
A
Advise the patient to leave her current
living situation immediately
B
Ask her to bring her husband to her next
appointment
C
Assess her immediate safety and develop a
safety plan
D
Report the husband to the police
E
Request psychiatry consultation
Key Point and Education Objective

Manage a patient who is a victim of
intimate partner violence.

The primary responsibility of the provider
for a patient who is a victim of intimate
partner violence is to assist with health;
assess for safety; and provide validation,
support, and empathy.
Explanation

The primary responsibility of the provider for a patient who is a victim of
intimate partner violence is to assist with health; assess for safety; and
provide validation, support, and empathy.

Leaving the abuser is neither necessary nor recommended without a well
thought-out plan unless the patient is in imminent danger, in which case
immediate intervention is indicated. Advising victims of intimate partner
violence to simply leave the situation, to utilize a shelter, contact an
intimate partner violence counseling service, or press criminal charges is
generally not helpful as the circumstances surrounding intimate partner
abuse relationships are complex, and the abused individual may have
significant reasons for not pursuing these actions that need to be
understood. An appreciation of the individual circumstances in the context
of a supportive relationship will help in developing a plan that may
ultimately involve the use of these valuable resources.
Explanation

It is not recommended that the potential abuser be confronted
directly or legal action be undertaken as an initial step in most
cases as this may potentially put the victim in greater danger.

Psychiatry intervention may be necessary for refractory depression,
or when the patient is deemed a risk to harm herself or others.
However, this would not be an appropriate next step in
management of this patient.

A substantial number of patients remain in adverse relationships
yet demonstrate improved health and health outcomes after
disclosure of their situation with appropriate support and
management.
Domestic Violence
Diagnosis
Physical and psychological domestic violence are associated with significant
mental and physical health consequences for both male and female victims.
Abuse frequently starts or increases during pregnancy.
Characteristic findings:

exacerbations or poor control of chronic medical conditions

seeming nonadherence to medications

abdominal pain

sleep or appetite disturbances, fatigue, reduced concentration, or chronic
pain

depression, anxiety, acute or posttraumatic stress, somatization, and eating
disorders

suicide attempts and substance abuse

frequent appointment changes

STDs, HIV, unplanned pregnancies

visible bruises or injuries
Assess the risk of homicide, suicide, or serious injury. Inquire about:

escalating threats or abuse and escalating level of fear

stalking

weapons, especially firearms, in the home

sexual assault and abuse during pregnancy

recent separation or abuser's awareness of impending separation
Therapy

Initiate safety planning. Determine if the patient wants to leave home,
return home, or have the abuser removed from his or her household.
Refer the patient to a domestic violence advocate.
Question 33
A
75-year-old woman is evaluated during a follow-up examination for
recently diagnosed symptomatic peripheral arterial disease. The
patient has hypothyroidism, hypertension, atrial fibrillation, and smokes
cigarettes (30-pack-year history). Her current medications are
diltiazem, warfarin, hydrochlorothiazide, levothyroxine, calcium, and
vitamin D.
On
physical examination, she is afebrile, blood pressure is 140/82 mm
Hg, pulse rate is 66/min, and respiration rate is 12/min. BMI is 21.
Posterior tibialis and dorsalis pedis pulses are diminished bilaterally
(1+); the skin on the anterior aspect of the lower legs is shiny and
hairless. Heart rhythm is irregularly irregular and without murmurs.
Neurologic and musculoskeletal examinations are normal.

Laboratory studies:

Total cholesterol
238 mg/dL (6.16 mmol/L)

HDL cholesterol
36 mg/dL (0.93 mmol/L)

LDL cholesterol
165 mg/dL (4.27 mmol/L)

Triglycerides 205 mg/dL (2.32 mmol/L)

Serum creatinine
0.9 mg/dL (79.6 µmol/L)
Answer Choice
In addition to strongly recommending smoking
cessation, which of the following is the safest
treatment for this patient?
A
B
C
D
Atorvastatin
Pravastatin
Rosuvastatin
Simvastatin
Answer Choice
In addition to strongly recommending smoking
cessation, which of the following is the safest
treatment for this patient?
A
B
C
D
Atorvastatin
Pravastatin
Rosuvastatin
Simvastatin
Key Point and Education Objective

Treat elevated LDL cholesterol level

In patients who require lipid-lowering
therapy and who are taking multiple
medications, a statin that is renally
metabolized, such as pravastatin, has a
lower risk of drug-drug interactions
Explanation
Pravastatin is the safest choice for lowering LDL cholesterol level in this
patient. She has recently diagnosed peripheral arterial disease, which is
associated with atherosclerosis; her goal LDL cholesterol level is, therefore,
less than 100 mg/dL (2.59 mmol/L) . Pravastatin is one of the preferred
statins in patients who are being treated with multiple medications.
Statins should be considered first-line therapy for lowering LDL cholesterol
levels in this patient, as studies have shown that older patients (ages 65-80
years) derive similar benefit as younger patients for secondary prevention
of cardiovascular disease. However, advanced age is also a risk factor for
statin-related myopathy, and therapy should be chosen carefully to
minimize this risk. Female sex, small body frame, hypothyroidism, statin
dosage, and treatment with multiple medications also influence the
likelihood of developing statin-related myopathy. Pravastatin is metabolized
by the kidneys; therefore, its concentration will be unaffected by
cytochrome isoenzymes that affect the metabolism of other statins or
warfarin.
Explanation
In contrast, atorvastatin, lovastatin, and simvastatin are primarily metabolized
through the cytochrome P-450 3A4 isoenzyme, and treatment with these
medications in combination with diltiazem can increase serum statin levels,
placing the patient at higher risk for statin myopathy. These statins should
not be combined with diltiazem in a patient who is at already high risk for
statin-induced myopathy based on her age, small body frame,
hypothyroidism, and multiple medications.
Rosuvastatin and fluvastatin are metabolized through the cytochrome P-450
CYP2C9 isoenzyme, and would effectively lower this patient's LDL
cholesterol level. However, rosuvastatin may affect the metabolism of
warfarin, leading to an increased INR. Caution is therefore necessary when
combining these medications, and this is not the safest choice for this
patient.
Question 34
A
30-year-old woman is evaluated for hyperlipidemia. Medical history
is significant for type 1 diabetes mellitus, hypothyroidism, and
hypertension. She is planning pregnancy. Her father was diagnosed
with coronary artery disease at the age of 47 years. Her current
medications are levothyroxine, hydrochlorothiazide, insulin glargine,
and insulin aspart.
On
physical examination, vital signs and the remainder of the physical
examination are normal.

Laboratory studies:

Hemoglobin A1c
8.1%

Total cholesterol
223 mg/dL (5.78 mmol/L)

HDL cholesterol
67 mg/dL (1.74 mmol/L)

LDL cholesterol
140 mg/dL (3.63 mmol/L)

Triglycerides 90 mg/dL (1.02 mmol/L)
Answer Choice
In addition to recommending therapeutic lifestyle changes,
which of the following is the most appropriate
management of this patient's lipid levels?
A
B
C
D
Colesevelam
Ezetimibe
Gemfibrozil
Simvastatin
Answer Choice
In addition to recommending therapeutic lifestyle changes,
which of the following is the most appropriate
management of this patient's lipid levels?
A
B
C
D
Colesevelam
Ezetimibe
Gemfibrozil
Simvastatin
Key Point and Education Objective

Treat hyperlipidemia in a woman who
desires pregnancy.

Bile acid sequestrants are an option for
reducing LDL cholesterol levels in women
with hyperlipidemia who wish to become
pregnant.
Explanation
This patient should be started on colesevelam. She has several risk factors for
cardiovascular disease, including poorly controlled diabetes mellitus, hypertension,
dyslipidemia, and a family history of premature myocardial infarction. Her goal LDL
cholesterol level is below 100 mg/dL (2.59 mmol/L).Therapeutic lifestyle changes,
which include a low-saturated fat diet and at least 120 minutes of aerobic exercise
weekly, will reduce LDL cholesterol levels by 7% to 15%. Thus, this patient needs
additional therapy to achieve her LDL cholesterol goal.
Ezetimibe is a cholesterol absorption inhibitor that can reduce LDL cholesterol levels
by up to 19%. Treatment with ezetimibe has not been shown to have beneficial
effects on cardiovascular morbidity or mortality. Moreover, ezetimibe is FDA
pregnancy class X, and should be avoided in women who may become pregnant.
Gemfibrozil is a fibric acid that is typically used for the treatment of
hypertriglyceridemia. It reduces LDL cholesterol levels by 10% or less; in addition,
gemfibrozil monotherapy in patients with hypertriglyceridemia can actually raise
LDL cholesterol levels. Gemfibrozil is not contraindicated in pregnancy (FDA
pregnancy class C) but would not be effective for achieving this patient's LDL
cholesterol goal.
Explanation
Although statins (such as simvastatin) are typically the first-line treatment for
lowering LDL cholesterol levels, statins are teratogenic (FDA pregnancy
class X) and should be avoided in women who may be or wish to become
pregnant. Colesevelam, which is a bile acid sequestrant that lowers LDL
cholesterol levels by up to 18%, is the best initial treatment option for this
patient. Colesevelam is FDA pregnancy class B and so is safe to use in
premenopausal women who are sexually active. Bile acid sequestrants have
been shown to reduce the risk of coronary heart disease in primary
prevention trials. The most common side effects associated with bile acid
sequestrants include constipation, abdominal pain and bloating, and
flatulence. Bile acid sequestrants can bind to and reduce the absorption of
other drugs; this effect can be minimized by administering the other drugs
1 hour before or 4 hours after taking a bile acid sequestrant.
Question 24
A
physician is asked to advise the Pharmacy and Therapeutics
Committee of the hospital regarding a new drug to prevent deep
venous thrombosis (DVT), drug “Z.” The physician reviews a recent
randomized controlled trial of 5000 patients that compared drug Z
with drug C, which is commonly used and is on the hospital's
formulary.The following data are abstracted from the trial:
Study results:
Drug
Drug Z (n = 2500)
Drug C (n = 2500)
DVT Cases
25
50
Answer Choice
Based
on these data, how many patients need to be
treated (number needed to treat, NNT) with drug Z,
compared with drug C, to prevent one extra case of DVT?
A
B
C
D
E
1
2
25
100
167
Answer Choice
Based
on these data, how many patients need to be
treated (number needed to treat, NNT) with drug Z,
compared with drug C, to prevent one extra case of DVT?
A
B
C
D
E
1
2
25
100
167
Explanation

The number needed to treat (NNT) with drug Z compared with drug C to prevent
one additional case of deep venous thrombosis (DVT) is 100.

Absolute risk (AR) is the risk of a specific disease based on its actual occurrence, or
its event rate (ER), in a group of patients being studied, and is expressed as:

AR = (patients with event in group) / (total patients in group)

As seen in the table, in this study, the AR for DVT in the group treated with drug Z
is 25/2500, or 1%, and the AR for the group treated with drug C is 50/2500, or 2%.

Often, the event rate of a disease in an experimental group (EER) is compared with
the event rate in a control group (CER). When the risk between groups is reduced,
this difference is termed the absolute risk reduction (ARR), or if the outcome is of
benefit, the difference is called the absolute benefit index (ABI). In this case, patients
treated with drug Z (EER) appear to benefit from treatment with a lower risk of
DVT than patients in the group treated with drug C (CER). This is expressed as:

ABI = | EER − CER |

ABI = |1% − 2% | = 1% or 0.01

This means that treatment with drug Z benefits patients compared with drug C by
lowering the risk of DVT from 2% to 1%, or an absolute difference of 1%.
Explanation

Assessing treatment studies using absolute measures also allows determination of
“numbers needed,” which are estimates of the clinical magnitude of the differences
between treatments. In this case, the NNT indicates the number of patients needed
to be treated with drug Z, compared with drug C, to obtain one additional
beneficial outcome. The NNT is calculated as:

NNT = 1/ABI

NNT = 1 ÷ 0.01 = 100

This means that 100 patients would need to be treated with drug Z compared with
drug C in order to prevent one additional case of DVT.

Treatment study results may also be reported as relative measures; these measures
compare the ratio of two outcomes without regard to the actual frequency of the
outcome in a given study population. In this case, treatment with drug Z leads to a
50% reduction in risk of DVT compared with treatment with drug C (25 compared
with 50 events), even though the actual frequency of DVT in the study populations
does not exceed 2%. Therefore, outcomes expressed in relative terms usually
appear of greater magnitude than when expressed in absolute terms; they also do
not allow calculations of number needed to estimate clinical impact.
Biostatistics
Sensitivity, Specificity, Predictive Values, and ROC Curves
Sensitivity
= (all true-positive test results) / (true-positive and false-negative test results). Remember SNout:
Sensitive test that is Negative rules OUT disease.
Specificity
= (all true-negative results) / (true-negative and false-positive results). Remember SPin: Specific test that is
Positive rules IN disease.
PPV
= (true-positive test results) / (all positive test results). PPV answers the question, “Given a positive test result,
what is the probability the patient has the disease?”
NPV
= (true-negative test results) / (all negative test results). NPV answers the question, “Given a negative test
result, what is the probability the patient does not have the disease?”
A
ROC curve is a graph of the sensitivity vs. (1 − specificity). In medicine, a ROC analysis provides tools to select
tests with optimal performance characteristics. The cut-point with the best combined sensitivity and specificity will
be closest to the upper left corner. The test with the greatest overall accuracy will have the largest area under the
ROC graph.
Don't Be Tricked
As
the prevalence of a condition increases, the PPV increases and the NPV decreases.
Changes
in prevalence do not alter the sensitivity or specificity.
Likelihood Ratios
The
LR is a measurement of the odds of having a disease independent of the disease prevalence.
You must first assess the patient's pretest probability of having a disease before applying the LR of
the test/finding to calculate the posttest probability.
Positive
LR = (sensitivity) / (1 − specificity); negative LR = (1 − sensitivity) / (specificity).
Positive
LR answers the question, “How much more likely is a person to have the disease given a
positive test result?”
LRs
of 2, 5, and 10 increase the probability of disease by approximately 15%, 30%, and 45%,
respectively.
LRs
of 0.5, 0.2, and 0.1 decrease the probability of disease by approximately 15%, 30%, and 45%,
respectively.