24th annual topics in the tropics seminar december 9...
TRANSCRIPT
24th ANNUAL
TOPICS IN THE TROPICS
SEMINAR
DECEMBER 9-12, 2015
F R I D A Y
The 24th Annual Topics in the Tropics Schedule
Friday, December 11, 2015 7:00 am Parkinson’s Disease: What’s new, what’s not
Dr. Kobylinski 8:00 am Top 10 Do’s and Don’ts of Dermatology
Dr. Rosamilia 9:00 am 7TH ANNUAL DAVID GWINN MEMORIAL LECTURE
Salivary Gland Disorders Mr. Valdez MPAS, PA-C
10:00 am Antimicrobial Changes: What is new and are the old still useful? Dr. Medico
11:00 am Subtle Nuances of Primary Care Dr. Chittalia
12:00 pm Meeting Adjourns
*Schedule is subject to change
Faculty and Planning Committee Disclosure
As an accredited provider of continuing education for health professionals, Geisinger Health System must ensure balance, independence, objectivity, and scientific rigor in each of its educational activities. All persons in a position to control the educational content of a sponsored activity (e.g. planners, presenters) must disclose to the audience any relevant financial relationships that they have with commercial interests. Relevant financial relationships may include such things as grants, research support, employment, consulting, stock ownership, or speakers’ bureau membership. Any identified conflicts of interest must be resolved prior to the activity. The intent of this disclosure is not to prevent planners or presenters with financial relationships from participating, but rather to provide learners with information on which they can make informed judgments regarding the educational content. It remains for the audience to determine whether an individual’s relationships influence the presentation with regard to exposition or conclusion. If you perceive commercial bias, please note it in the activity evaluations, notify onsite staff persons, and/or call our anonymous toll free hotline at 1-877-557-7447. The following persons in a position to control educational content of this activity have disclosed no relevant financial relationships with commercial interests: Christopher Berry, MS, PA-C Cybele Pacheco, MD Aliasgar Chittalia, MD Lorraine Rosamilia, MD Michael Gallagher, PA-C Michael Ryan, DO Charles Haney, PA-C Miguel Valdez, MPAS, PA-C Maria Kobylinski, MD Heloise Westbrook, MD, PhD Charles Medico, PharmD Commercial Support None Objectives: At the completion of this course, the participant should be able to:
• list the signs and symptoms of Peritonsillar abscess • define the current indications/contraindications to thrombolytic therapy • review the newest recommendations in vaccinations as well as discuss several
vaccinations that have just been approved for use • review presentation of plantar fasciitis, treatment options, when to refer, what to
tell your patient • apply strategies to assess and stratify women into high risk and at risk categories
for cardiovascular disease • discuss pharmacological and nonpharmacological treatment of neuropathic pain • review the various treatment options for Parkinson’s Disease • clarify common dermatologic diagnostic and treatment pearls for primary care
providers
• recognize the clinical presentation of infectious, inflammatory, obstructive and neoplastic disorders of salivary glands
• identify the place in therapy of the newer antimicrobial agents and compare and contrast newer agents with the current standards of therapy
• discuss tips in clinching diagnosis and managing various common presentations seen in primary care with confusing differential diagnosis
• describe recent changes in diagnosing pediatric infections in the ED • outline systems-based prevention strategies for herpes zoster in health care
institutions, including hospital isolation policies and zoster vaccination • identify the key medications recently approved by the FDA • define specific complications associated with SAH and care plan • outline the ENT approach to Inhalant Allergy, Food Allergy and Sting Allergy
Accreditation Geisinger Health System is accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. Designation Statement Geisinger Health System designates this live activity for a maximum of 18 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Geisinger Health System designates this activity for 18 contact hours for nurses. Nurses should claim only credit commensurate with the extent of their participation in the activity. This live activity is approved for 18 contact hours (1.8 CEUs) of continuing pharmacy education credit (0266-0000-15-022-L01-P).
Thank you for attending today’s conference. You can use the link below to the on-line evaluation form, which will also be e-mailed to you after the activity. If you prefer to use your Smart Phone and/or device, you can click on the QR Code below to access the evaluation form. Participants must submit an evaluation in order for the activity to be thoroughly evaluated. Activities that are not sufficiently evaluated may not be eligible for credit.
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Thank you.
https://go.geisinger.org/topicsfri
Certificates are no longer provided for registrants. Please follow the instructions below how to access your credits.
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1
Parkinson’s Diseasetitle
Presenter: Maria “Suzy” Kobylinski
Chairman CPSL
Creator: Dr. C. Ramanan, M.D.
History
• In Western medical literature it was described by the
physician Galen as “shaking palsy” in 175 AD.
• In 1817 a detailed medical essay was published on the
subject by London doctor James Parkinson.
• Jean-Martin Charcot was the first to truly recognize the
importance of Dr. Parkinson’s work and renamed the
disease which was formerly named paralysis agitans
(shaking palsy) after him.
| 2
Famous Personalities
| 3
2
| 4
Natural History
• Begins between 40 and 70 years of age.
• Peak age of onset at sixth decade.
• Infrequent before 30 years of age.
• More common in men.
• Trauma, emotional upset, overwork, exposure to cold,
rigid personality etc. are suggested to be the
predisposing factors to the disease but none have
evidence.
• Disease observed in all countries and all races.
| 5
Parkinsonism and Parkinson’s Disease
(idiopathic)
• Parkinsonism is a clinical syndrome characterised
primarily by bradykinesia, with associated increased tone
(rigidity), tremor and loss postural reflexes.
• When Parkinsonism features are present in a person
without any established etiology it is called Parkinson’s
Disease.
| 6
3
Etiology
| 7
Genetics
• Genetic abnormalities resulting in protein misfolding and
accumulation and mitochondrial dysfunction are found to
be responsible for causing PD.
• Protein accumulation can be due to increased formation
or impaired clearance.
• Mutation in the Park1 gene encoding the protein alpha-
synuclein, a main component of lewy body, on the
chromosome 4q are seen in early onset (mean age 46
years) Parkinson’s Disease.
| 8
Genetics
• Mutations in parkin (a ubiquitin ligase that attaches
ubiquitin to misfolded proteins to promote their transport
to the proteasome for degradation) and UCH-L1 (which
cleaves ubiquitin from misfolded proteins to permit their
entry into the proteasome) are causative in other cases
of familial PD.
• Mitochondrial dysfunction has also been implicated in
familial PD. Genes involved (parkin, PINK1, and DJ1).
• Having first degree relative with PD confers a 2-3 times
increased risk of developing Parkinson’s Disease.
| 9
4
| 10
What is Parkinson’s Disease?
• Defined as
“Involuntary tremulous motion, with lessened muscular
power, in parts not in action and even when supported,
with a propensity to bend the trunk forward, and to pass
from a walking to running pace: the senses and the
intellects being uninjured.”
| 11
Clinically
• The presence of two out of three cardinal features of
bradykinesia, rigidity, and tremor; postural instability
tends to occur later.
• A good clinical response to levodopa; and
• No ‘atypical’ features suggestive of another parkinsonian
syndrome.
| 12
5
Pathologically
• There is extensive loss of pigmented dopaminergic
neurons in the substantia nigra and the presence of lewy
bodies.
• Clinical features do not emerge until >60-80% dopamine
loss.
| 13
Anatomy
| 14
Functions of Basal Ganglia
• Plays an important role in:
• planning and programming of movement by selecting and
inhibiting specific motor synergies.
• cognitive processes, primarily the caudate nucleus, including the
awareness of the body orientation in space, ability to adapt
behavior as task requirements change and motivation.
| 15
6
| 16
| 17
Cardinal Features
RIGIDITY
LEAD PIPE – Trunk & Lower Limb
Trunk – Stooped and Flexed
COG WHEEL – Upper Limb
HYPOKINESIA & BRADYKINESIA
Slowness in initiating and repeating
voluntary movements despite
normal strength
TREMORS
RESTING – 4 to 6 Hz
With movement and attention
Fingers (Common)
POSTURAL – 8 to 10 Hz
Persist on Movement
| 18
T
E
T
R
A
D
GAIT/POSTURAL REFLEXES DISTURBED
Difficulty in maintain balance
Slow to start walkingShortened stride
Rapid small steps (Tendency to run)
Reduced arm swing
Difficulty in stopping suddenly
Impaired balance on turning
7
Tremors
• Often involves the hand.
• Pill-rolling tremors (four per second) involving thumb
and fingers are characteristics.
• Typically present when the hand is at rest (hence the
term RESTING TREMOR)
• Voluntary movements dampens the tremors
momentarily.
• Complete relation (sleeping) greatly reduces or
abolishes the tremor.
• Also known as alternating tremors due to alternating
burst of activity in agonist and antagonist in EMG.
| 19
Second common type is
• A fine, seven to eight per second tremors of the
outstretched hands and fingers.
• Persists throughout voluntary movements.
• Not evident in resting position.
• More easily suppressed by relaxation.
• Lacks the alternating burst of action potential unlike
resting tremors and resembles essential tremors.
• Parkinson’s disease patients may have either type of
tremor or both.
| 20
Rigidity
• Muscles are continuously or intermittently firm and tense.
• Present when patient is in awakened state, even when
appearing quiet and relaxed.
• Unlike spasticity it lacks the initial
“free interval” on passive flexion
thus having the quality of bending
a lead pipe.
• Limb does not resume its original position as happens in
spasticity.
| 21
8
Rigidity
• Rigidity involves both flexor and extensor muscles but
predominant in flexors.
• Small muscles of face, tongue, larynx, are also affected.
• Cogwheel phenomenon: Rigidity with superimposed
tremor. Passive flexion of hypertonic muscles causes
rhythmically interrupted ratchet like resistance.
• Once rigidity develops it is constantly present.
• Initially unilateral later becomes bilateral.
• Tendon reflexes are not enhanced.
• Babinski is negative.
| 22
Hypokinesia and Bradykinesia
Hypokinesia is defined as
“Disinclination on the part of the patient to use an
affected part and to engage it freely in all the natural
actions of the body.”
• The frequent automatic habitual movements are absent or
reduced.
• Blinking is infrequent & face lacks expressive mobility.
• Reduced arm swing while walking.
• On looking to one side eyes move but not the head.
• There is a lack of the small “movements of cooperation” (as in
arising from the chair without first adjusting the feet).
• Handwriting becomes small (Micrographia)
| 23
Micrographia
Normal
After developing
Parkinson’s disease
| 24
9
Hypomimia
| 25
Face looks
expressive
mobility
(masked facies
or hypomimia)
Infrequency of
blinking, 5-10 per min
Drooling of saliva
Soft voice and
rapid monotonous
speech
Bradykinesia
• Refers to reduced velocity of the movement, or the time
from onset to completion of movement is slower than
normal.
• Reaction time (time interval between the command and
the first contraction of the muscle) is also increased.
• Salvia is not swallowed as quickly as it is produced.
• Inability to carry our quick (ballistic) movements.
• Inability to inhibit blinking in response to a tap over the
bridge of the nose or glabella (Myerson sign).
| 26
Parkinsonian Gait
• Involuntary flexion of the trunk limbs
and the neck.
• Hesitation in starting to walk.
• Steps are short and the feet barely
clears the ground as patient shuffles
along.
• Once walking started patient takes
increasingly short and rapid steps as
though trying to catch up to his centre
of gravity (Festination).
• Freezing briefly when encountering
doorways or other obstacles.| 27
10
Parkinsonian Gait
• Diminished or reduced arm swing.
• Turning en bloc.
• Inability to make appropriate postural adjustments to
tilting and falling.
• Anticipatory and compensatory righting reflexes are
impaired.
| 28
Additional Features
| 29
PAIN:
• Initially the only complaints may be of
aching of the back, neck, shoulders, or
hips and of vague weakness.
DYSTONIA:
• Persistent extension or clawing of the
toes, jaw clenching, and other
fragments of dystonia, often painful,
may be present but are not usually
early findings. (These are particularly
resistant to treatment.)
Additional Features
BEHAVIORAL CHANGES:
• Depression, anxiety, dementia, hallucinations.
• Impaired memory is usually not a major feature of PD.
• Dementia correlates with increase in number of lewy bodies.
AUTONOMIC DYSFUNCTION:
• Hypotension (levodopa, dopa agonists)
• Constipation (anticholinergics)
• Bladder dysfunction.
• Sleep disturbances.
• Sexual dysfunction.
• Hyperhidrosis.
• Seborrhea.
• Leg edema. | 30
11
Investigations
• Only useful for research purpose.
• Diagnosis is only based on clinical features.
• Imaging can be useful in difficult cases or research
studies.
• Genetic testing may be useful in identifying at-risk
individuals in research setting.
| 31
Treatment
Pharmacotherapy
Surgery
Physiotherapy
| 32
Pharmacotherapy
• Dopamine agonists
• Pramipexole, ropinirole
• Carbidopa/levodopa
• COMT inhibitors
• Entacapone, tolcapone
• Anticholinergics
• Trihexyphenidyl, benztropine
• MAOIs
• Selegiline, rasagiline
• Amantadine
| 33
12
Dopamine Synthesis
| 34
Pharmacologic basis of treatment
| 35
Mode of action
| 36
13
How PD medications work
| 37
Levodopa+Carbidopa:
• The most effective symptomatic treatment for PD and the
gold standard against other drugs.
• Combination reduces oral closes and reduce acute
dopaminergic side effects like nausea, vomiting, and
orthostatic hypotension.
• Combinations of carbidopa-levodopa are available in a
1:10 or 1:4 ratio and the benserizide-levodopa
combination in a 1:4 ratio.
• The initial dose of levodopa-carbidopa is typically one-
half to one of a 25/100-mg tablet given two or three
times daily and increased slowly until optimum
improvement is achieved.| 38
• Dietry protein interferes with absorption of levodopa.
• Taking medications 1 hour before food or 2 hours after
food can lead to more predictable and effective
absorption and improved stability.
• Controlled release levodopa reduces the number of
doses but associated with slow onset of action
particularly in morning. Addition of conventional dose at
this time can provide a initial ‘kick in’.
• Mild off periods respond well to small supplemental
doses in fast acting form like dispersible tablets which
acts rapidly but short acting.
| 39
14
Side effects of levodopa
• Anorexia, nausea, and vomiting-stimulation of ctz.
• Tachycardia, ventricular extra systoles and Hypotension.
• Psychotic patients-exacerbation of symptoms.
• Vitamin B6 (pyridoxine) increases peripheral degradation
of levodopa.
| 40
Motor complications of levodopa:
These are limitation of the long-term use of levodopa
therapy.
“wearing off” phenomenon:
• Each dose of levodopa effectively improves mobility for a
period of time, perhaps 1-2 hours, but rigidity and
akinesia return rapidly at the end of the dosing interval.
• The occur at later stage of the disease.
• Increasing the dose and frequency of administration can
improve this situation, but this often is limited by the
development of dyskinesias.
| 41
On-Off phenomenon:
• In more advanced states, patients may cycle between “on”
periods complicated by disabling dyskinesias and “off” periods in
which they suffer severe parkinsonism.
• This may occur in a matter of minutes or from one hour to the
next.
Peak-dose dyskinesia:
• Many patients develop dyskinesias at the time of maximal clinical
benefit and peak plasma concentration.
• They are usually choreiform in nature but can manifest as
dystonia, myoclonus, or other movement disorders.
Diphasic dyskinesias:
• Occur as the levodopa dose begins to take effect and again as it
wears off. | 42
15
Changes in motor response associated with
chronic levodopa treatment
| 43
| 44
COMT-inhibitors
• Reduces “off” time and prolongs “on” time and more
beneficial in patients treated with levodopa+carbidopa
combination having motor fluctuations.
• Tolcapone and entacapone are approved drugs.
• Side effects are dopaminergic (nausea, vomiting,
increased dyskinesias).
• Diarrhea = tolcapone > entacapone.
• Fulminant Hepatic necrosis reported with talcapone so
LFT monitoring is important.
• It is not reported with entacapone.
• Discoloration of urine is reported.
| 45
16
MAO-B inhibitors:
• Block central dopamine metabolism and increase synaptic
concentrations of the neurotransmitter.
• Reduce “off” time when used as an adjunct to levodopa in
patients with motor fluctuations.
• Well tolerated and reduces the required dose of levodopa.
• Early reports of possible neuroprotective effects of selegiline
have not been supported by long-term studies.
• Selegiline is metabolized to methamphetamine and
amphetamine, whose stimulating properties may produce
insomnia. But not rasageline.
• High dose of these drugs can cause hypertensive crisis
known as cheese reaction.
| 46
Amantadine:
• Originally introduced as an antiviral agent.
• It is the only anti parkinsonian drug that improved
levodopa induced dyskinesia.
• According to recent studies it acts by inhibiting NMDA
receptors, increases presynaptic dopamine reuptake and
release.
• Less efficacious than levodopa.
• Has little effect on tremor, but it is more effective than the
anticholinergics against rigidity and bradykinesia.
• Adverse effects are livido reticularis, ankle edema,
urinary dysfunction, glaucoma, and particularly cognitive
impairment.| 47
Dopamine agonists:
• Longer duration of action than levodopa
thereby causing lesser risk of developing
dyskinesias.
• Ergot derivatives are not used now due major
cardiac side effects.
• In early PD it delays the need to start levodopa
therapy.
• In late PD it helps to reduce the dose of
levodopa.
• Apomorphine is available only as IV preparation.
• Rotigotine is available as transdermal patches.| 48
17
• Adverse effects like hypersexuality and pathological
gambling also seen.
• Younger patients less than 60 yrs who are at more risk of
developing dyskinesia are more likely to tolerate
agonists.
• Agonist monotherapy is associated with fewer motor
complications.
• Agonist monotherapy is unlikely to be adequate for more
than 5 years.
• Aim of agonists monotherapy is to delay the levodopa
therapy and not to avoid it altogether.
| 49
Anticholinergics:
• Used in early stages when symptoms are not
troublesome.
• Useful against tremors but not against other symptoms
of PD.
• Side effects are dry mouth, blurring of vision, glaucoma,
hallucinations and prostatic obstruction.
• Use is limited in elderly due to the side effects.
| 50
| 51
18
Surgery
• Steriotactic lesions placed in motor cortex improved
tremors but produced motor deficits.
• Lesions placed into the ventral intermediate (VIM)
nucleus of the thalamus reduced contralateral tremor
without inducing hemiparesis but not improved other
symptoms.
• Lesions placed in the globus pallidus internal (GPi)
improved rigidity and bradykinesia as well as tremor.
• Pallidotomy was also associated with marked
improvement in contralateral dyskinesia.
• These procedures were not optimal for patients with
bilateral disease.| 52
Deep brain stimulation
• An electrode is placed into the target area and
connected to a stimulator.
• DBS simulates the effects of a lesion without
necessitating a brain lesion.
• It does not require making a lesion in the brain and is
thus suitable for performing bilateral procedures with
relative safety.
• DBS for PD primarily targets the subthalamic nucleus
(STN) or the GPi. It provides dramatic results,
particularly with respect to “off” time and dyskinesias.
| 53
Management of non-motor symptoms
• Depression – SSRI’s. Antidepressants should not be
withheld, particularly for patients with major depression.
• Anxiety-Short acting benzodiazepines.
• Psychosis-low dose neuroleptics: Clozapine is most
effective (A.E: Agranulocytosis). Quetiapine is also used.
• Dementia-Levodopa and other dopaminergic drugs can
aggravate cognitive function in demented patients and
should be stopped or reduced.
• Anticholinesterase agents such as rivastigmine and
donepezil reduce the rate of deterioration. Memantine,
an antiglutamatergic agent, may also provide benefit for
some PDD patients.| 54
19
• Orthostatic hyptension – Adding salt to the dies and
elevating the head of the bed. Low doses of
fludrocortisol (Florinef) or midodrine control most cases.
• Sexual dysfunction can be helped with sildenafil or
tadalafil.
• Urinary problems – cholinergics are helpful.
• Constipation – Laxatives
• Sleep disturbances – low dose clonazepam.
| 55
Other aspects of management
• Physiotherapy, Occupational therapy, Speech therapy
are helpful in advanced cases with disability.
• Intensive social support in the community is necessary.
• Residential care may be the only option in some cases.
| 56
Recent advances in treatment
• Levodopa-carbidopa Gel (duodopa): continuously
delivered through duodenostomy or jejunostomy tube
into intestine. More invasive. Constant levels are
maintained.
• Dopamine agonists:
PARDOPRUNOX, has progressed to Phase III trial.
APLINDORE, is being studied in a Phase II trial.
LISURIDE, which is in the form of a skin patch and is
already marketed in Europe, has progressed to a
Phase II trial.
| 57
20
• MAO-B inhibitors:
NEBICAPONE, has shown promising results in preliminary trials.
SAFINAMIDE, is being studied in a Phase III trial.
• Non dopaminergic agents:
Adenosine A2A antagonists: ISTRADEFYLLINE, was taken to
Phase III trials, but it failed to prove effective.
FIPAMEZOLE (JP-1730), SCH-420814, BIIA-014 and Lu AA4707 –
are in earlier phases of development.
| 58
• FP0011, a compound that reduces central glutamate
levels, is now being studied in a Phase II trial.
• A metabotropic glutamate (mGlu5) receptor antagonist
has completed has completed a Phase I trial.
• Cell-based therapies (such as transplantation of fetal
nigral dopamine cells or dopamine neurons derived from
stem cells), gene therapies, and trophic factors are
under experimentation.
| 59
SYMPTOMS/SIGNS ALTERNATIVE DIAGNOSIS TO
CONSIDER
Falls as first symptom PSP
Exposure to neuroleptics Drug-induced parkinsonism
Onset prior to age 40 If PD think of genetic cause
Associated unexplained liver disease Wilson’s disease
Early hallucinations Lewy body dementia
Sudden onset of parkinsonian symptoms Vascular parkinsonism
Dementia as 1st symptom Lewy body dementia
Prominent orthostasis MSA-p
Early dysarthria MSA-c
Lack of tremors Various parkinsonian plus syndromes
High frequency (8-10 Hz) symmetric
tremors
Essential tremor
| 60
21
THANK
YOU!
| 61
1
A LIST:
DO’S AND DON’TS
OF DERMATOLOGY
Lorraine L. Rosamilia, MD FAADGeisinger Health System Department of Dermatology, State College, PA
Disclaimer
No conflicts of interest to disclose
DO…
1. Know how to properly describe skin lesions and eruptions
2. Pick favorite generic low, medium, and high potency topical steroids for appropriate usage
3. Understand how to prescribe topical retinoids
4. Recommend sun protection to all rosacea patients, educate on other triggers, and explain limitations of medical therapy
5. Recommend a consistent home therapy regimen to all wart patients
6. Discuss daily skin care for atopic patients
7. Learn how to perform KOH and scabies preps
8. Know what ingredients are in common OTC topical preparations
9. Send all lesions removed on a patient to pathology, and understand how to read a pathology report
10. Ensure that skin cancer patients have regular skin checks and perform self skin exams
2
DON’T…
1. Cryo, curette, or partially remove any lesion that you think might be melanoma
2. Cryo/heavily destroy a wart in the periungual region
3. Use combination topical antifungal/potent steroid preparations
4. Treat a patient with prednisone right before you request a dermatology consult or a skin biopsy
5. Give psoriasis patients prednisone without proper instruction and follow-up
6. Discourage possible use of isotretinoin to patients/parents
7. Forget the cosmetic outcome after cryotherapy or biopsy
8. Treat every fungal infection as yeast
9. Assume every nail dystrophy is fungus
10. Misdiagnose stasis dermatitis as bilateral leg cellulitis
In-office procedures
Completely remove lesions suspicious for melanoma
to provide proper prognostic Breslow depth
measurement (excision to fat)
In-office procedures
Send all lesions to pathology/dermatopathology
for review, and know who to call if you do not
understand a report
3
In-office procedures
Cryotherapy and biopsy procedures can cause
scarring and dyspigmentation
Steroids
Prednisone will improve psoriasis for a short period
of time, and it recurs/rebounds soon after its
withdrawal
Steroids
Prednisone can diminish clinicopathologic diagnostic
findings
Steroid tapers for rashes like poison ivy require at
least 10-14 days of treatment to prevent rebound
Biopsy technique and timing depends on your
differential diagnosis
4
Steroids
There are innumerable topical steroid preparations, but prescribing a finite number of affordable agents addresses most skin indications
potency = (clobetasol),
betamethasone dipropionate
potency = triamcinolone
potency = hydrocortisone
Acne
Multiple-agent therapy for mild to moderate acne
involves proper education about medication
schedule, side effects, and expected results
Patients are rarely “allergic” to topical retinoids,
but they often cause irritation
BPO wash, topical retinoid, oral antibiotic
5
Isotretinoin
Isotretinoinis the
therapy for recalcitrant, severe and/or scarring acne, and its use is tightly regulated
Homework
Wart patients must use home therapy (retinoids,
salicylic acid, etc) between destruction visits
6
Homework
Atopic patients must moisturize/be moisturized
every day, particularly after bathing
is key
Homework
Rosacea patients should apply daily sunscreen and
avoid rosacea to control flares
Topical/oral antibiotics are effective for flushing
or erythema or telangiectases
Homework
Patients should know what skin cancer looks like and
what their own skin and loved ones’ skin looks like
Patients and their families should know how to
perform self skin exams, monitor for new or
changing skin lesions, and use sunscreen/sun
protection appropriately
7
ABCD
ABCD
8
Sunscreen
SPF – measures topical UVB protection
UPF – measures sun-protective clothing UVA/B
protection
‘broad spectrum’ (includes UVA)
SPF level
protection against skin cancer
and aging (≥SPF 15 and BS)
water resistance 40 or 80 min
9
Infection and infestation
Fungal rashes on the skin include candidiasis,
dermatophytosis, and seborrheic dermatitis among
others, and each is treated differently
Infection and infestation
Consider performing in-office KOH and scabies preps
Infection and infestation
Potent topical and systemic steroids increase the
severity of fungal skin infections
Not all patients respond to systemic therapy for
onychomycosis, so the risks and benefits need to be
weighed
10
Potpourri
Go to the pharmacy and note the ingredients of
commonly-used cosmetics and topical therapies for
warts, acne, athlete’s foot, wound care, and sun
protection
Embrace petroleum jelly
Potpourri
Bilateral leg
cellulitis is very
uncommon, so most
of these patients
have venous stasis
dermatitis and are
clinically stable
Teamwork
Set the groundwork. Get to know us. Ask questions.
Provide clinical history and lesion description in the
chart
Include topical medications in the patient’s
medication list
Decide which patients may need dermatology full
skin checks as part of health maintenance
Learn about Mohs surgery criteria and options in
your region
11
Which of the following is true?
1. Patients are often allergic to topical retinoids
like tretinoin (Retin A)
2. Clobetasol is a low-potency topical steroid
3. Topical and oral antibiotics improve the
erythema and flushing associated with
rosacea
4. Psoriasis usually flares after treatment with
oral prednisone
5. Bilateral leg cellulitis is a common entity
Which of the following is true?
1. Isotretinoin (formerly Accutane) is the most effective therapy for recalcitrant and/or scarring acne
2. It is acceptable/appropriate to curette a nevus or a lesion suspicious for melanoma
3. SPF (sun protection factor) refers to UVA and UVB ray protection
4. Azole topical antifungals are the best treatment for common tinea (ringworm)
5. Neosporin or triple antibiotic preparations are better than plain petroleum jelly for healing of wounds or surgical sites
12
DO…
1. Know how to properly describe skin lesions and eruptions
2. Pick favorite generic low, medium, and high potency topical steroids for appropriate usage
3. Understand how to prescribe topical retinoids
4. Recommend sun protection to all rosacea patients, educate on other triggers, and explain limitations of medical therapy
5. Recommend a consistent home therapy regimen to all wart patients
6. Discuss daily skin care for atopic patients
7. Learn how to perform KOH and scabies preps
8. Know what ingredients are in common OTC topical preparations
9. Send all lesions removed on a patient to pathology, and understand how to read a pathology report
10. Ensure that skin cancer patients have regular skin checks and perform self skin exams
DON’T…
1. Cryo, curette, or partially remove any lesion that you think might be melanoma
2. Cryo/heavily destroy a wart in the periungual region
3. Use combination topical antifungal/potent steroid preparations
4. Treat a patient with prednisone right before you request a dermatology consult or a skin biopsy
5. Give psoriasis patients prednisone without proper instruction and follow-up
6. Discourage possible use of isotretinoin to patients/parents
7. Forget the cosmetic outcome after cryotherapy or biopsy
8. Treat every fungal infection as yeast
9. Assume every nail dystrophy is fungus
10. Misdiagnose stasis dermatitis as bilateral leg cellulitis
Thank you!
1
P A
David H. Gwinn
Memorial Lecture
P A
Salivary Gland Disorders
Topics in the Tropics 2015
Miguel V Valdez PA-C
P AAnatomy
Classification
– Major
Parotids (Paired)– Facial nerve separates superficial
from deep lobe
– Medium
Submandibular (Paired)
Sublingual (Paired)
– Minor
Throughout oral cavity, palate, buccal mucosa, lip mucosa
2
P AAnatomy
P APhysiology
Saliva production
– Flow: 1-1.5 L/day 1 cc/min.
•70% of volume comes from the submandibulars
– •Submandibulars produce a higher proportion of mucous: mucin
– •More active at night.
P APhysiology
Functions of saliva
– Lubrication
– Cools food
– Enzymatic degradation of food
– Mediation of taste
– Antimicrobial functions
– High in Bicarbonate
3
P ASialoadenitis
Viral
– Mumps
– All others
Bacterial
– Staph (adults)
– Pseudomonas (peds ?????)
– Tuberculosis
P ASialoadenitis
Symptoms
– Swelling
– Pain
– +/- fever
– Salty taste in mouth
– Symptoms worsen with eating
P ASialoadenitis
Exam
– Swelling
– Erythema of skin
– Tenderness over the area
– May see pus expressed from duct
Stensen’s (parotid)
Wharton’s (submandibular)
– Bi-manual exam may reveal stone/mass
4
P ASialoadenitis
Treatment Hydration
Sialagogues (lemon drops)
Analgesics
+/- massage
– Antibiotics
Clindamycin seems to be drug of choice– Prefer---Amoxicillin/Clavulanate
Others that will cover Staph
May require pseudomonas coverage*****
– Surgery---very rare, if abscess present
P ASialolithiasis
“Stones”
Cause is unknown
– ? Dehydration
Most stones occur in submandibular glands
May be calcium carbonate or calcium phosphate
P ASialolithiasis
Symptoms
– Same as with infection
Swelling
Pain
+/- fever
Symptoms are much worse with eating due to obstruction
5
P ASialolithiasis
Exam
– Swelling
– Tenderness
– Redness
– May see or feel stone (bimanual exam)
P ASialolithiasis
Treatment
– Hydration
– Sialagogues
– Massage
– Antibiotics
– Remove stone
Intraoral
Excision of gland
P ASialoadenosis
Inflammation
– Nutritional (vitamin deficiency, anorexia)
– Endocrine issues (DM, hypothyroidism)
– Metabolic Problems (obesity, cirrhosis)
– Drug-induced
6
P ASialoadenosis
Exam
– Variable but almost always has gland enlargement, usually, parotid
Treatment
– Directed at suspected cause
P ARecurrent Parotitis of Childhood
May be related to sialoadenosis
– Has sialectasia
– True etiology unknown
– Many theories
Manifests as recurrent episodes of parotid infections
Usually around age 4-5
– Tend to outgrow it.
P ARecurrent Parotitis of Childhood
Exam Swelling
Pain
Redness
+/- fever
7
P ARecurrent Parotitis of Childhood
Treatment
– Hydration
– Sialagogues
– Massage
– Antibiotics
Some data suggests these children can go on to develop Sjogren’s Syndrome
P AInflammatory/Immune
Sjogren’s Syndrome
– Dry eyes, dry nose, dry mouth
– Swelling of the glands (usually parotids)
– Associated with autoimmune/connective tissue disorder, i.e., Lupus, Rheumatoid Arthritis
P AInflammatory/Immune
Sjogren’s
– Diagnosis
Can do salivary gland biopsy– Focal lymphocytic sialadenitis
Labs, SS-A, SS-B
Nothing is 100% for diagnosis
8
P AInflammatory/Immune
Sjogren’s
– Treatment
Sialagogues– Pilocarpine (Salagen)—stimulates
muscarinic cholinergic receptors
– Cevimeline (Evoxac) – same mechanism
Hydration
Artificial tears
Must monitor for development of Lymphoma—Lifelong
P ASialoceles/Mucocele
Minor salivary gland cysts
– Usually on the lip mucosa
– Requires no treatment but depends on patient
– Simple to excise
P ARanula
Salivary gland cyst
– Usually larger gland
– Usually Floor of mouth
– Can penetrate through Mylohyoid muscle, becomes a Plunging Ranula
Surgery usually required
9
P ANeoplasm
Salivary gland tumors
– Major glands—75% benign
– Medium glands—50 % benign
– Minor Glands – 25 % benign
P ANeoplasms
Benign tumors
– Pleomorphic Adenoma most common
– Wharton’s tumor (papillary cystadenoma lymphomatosum) next most common
P ANeoplasms
HIV
– Multiple cysts—bilateral****
10
P ANeoplasms
Malignant
– Mucoepidermoid—most common in parotid
– Adenoidcystic—most common in minor glands
– Acinic
– Adenocarcinoma--aggressive
P ANeoplasms
Malignant
– Squamous Cell
– Lymphoma
– Metastasis from other sites, such as Melanoma, renal cell, breast
P ANeoplasms
Diagnosis
– FNA– very helpful if +
– MRI
– CT
11
P ANeoplasms
Treatment
– Surgery
– Radiation
– Chemo
HIV-
– Rarely surgery
P ASalivary Gland Disorders
We have talked about many salivary gland disorders, most of which can be handled in the Primary Care setting.
It does require a certain level of comfort
Referral is indicated when dealing with neoplasms or when your comfort level has been reached.
P AThank you!
1
“New” Antimicrobials: You
Can Teach an Old Dog New
Tricks!
Charles Medico,PharmD,BCPS
Pharmacy Clinical Coordinator
Geisinger Medical Center
Danville, PA
| 2
| 3
Scope of the Problem?
• According to the CDC
• Antimicrobial resistance is one of the most serious health threats
world-wide
• 2 million antibiotic resistant infections per year in the USA
• Most resistant infections occur in community
• Most deaths occur in hospitals and nursing homes
| 3
2
Healthcare Advancements Driving the Need for
Effective Options
• Chemotherapy
• Transplant medicine including organ and bone marrow
• Immunomodulating treatments for autoimmune diseases
• Complex surgeries
• Dialysis
• Bloodstream infection is the second leading cause of death| 4
Resistance Contributes To:
• Costs
• Direct costs of resistance estimated to exceed $20 billion
• Additional $35 billion per year in lost productivity
• Death
• 23,000 die per year as a direct result of these infections
• Increased hospital length of stays
• Exposure to more expensive, less effective, and toxic medications
• Survivors more likely to have long term disability
| 5
Cause of Resistance
• Use of antibiotics
• Humans
• Most commonly prescribed drugs in human medicine
• 50% prescribed are inappropriate
• Food animals
• To prevent, control, and treat disease
• Promote growth
Do you think there is more use in humans or animals?
| 6
3
| 7
CDC Recommendations to Fight Resistance
• Prevent infections and prevent the spread of resistance
• Track resistant bacteria
• Improve the use of today’s antibiotics through
prescribing and stewardship
• Identified by CDC as the most important step to fight resistance
• Promote the development of new antibiotics and
developing new diagnostic tests for resistant bacteria | 8
| 9
4
| 10
Specific CDC Antimicrobial Threat Levels
| 11
Development of New Antibiotics
| 12
5
Teaching Old Dogs New Tricks
Seru
m P
-T C
oncentr
ation
Time
(hours)
1 2 3 4 5 6
MIC
30-minute
infusion
4-hour infusion
Prolonging infusion times for time-dependent antibiotics
Teaching an Old Dog New Tricks
Combining old products with new medications
| 14
Ceftazidime-avibactam
• Indications
• Complicated intra-abdominal infections used IN COMBINATION
with metronidazole
• E.Coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia
stuartii, Enterobacter cloacae, Klebsiella oxytoca, Pseudomonas
aeroginosa
• Complicated urinary tract infections, including pyelonephritis
• Above plus Citrobacter koseri, Enterobacter aerogenes, Citrobacter
freundii
| 15
6
Clinical Data
• Determination of efficacy of Avycaz was supported in
part by previous findings of the efficacy and safety of
ceftazidime.
• The contribution of avibactam to ceftazidime was
established in vitro and in animal models of infection
• 2 phase 2 trials one each for cIAI and cUTI with a total of
169 patients
• 101 patients CrCl <50 ml/min excluded from cIAI trial
• 68 patients CrCl <70 ml/min excluded from cUTI trial
| 16
Phase 3 cIAI Trial Data
• Avycaz plus metronidazole vs. meropenem
• 529 patients in each arm
| 17
Regimen Mortality Mortality if
CrCl >50
Mortality if
CrCl 30-50
Avycaz plus
metronidazole
2.5% (13/529) 1% (5/498) 25.8% (8/31)*
Meropenem 1.5% (8/529) 1% (5/494) 8.6% (3/35)
*Approved dose is 33% higher for CrCl 30-50 then that tested
Doses were studied using 30 min infusions but the approved
duration of infusion is 2 hours.
Adverse Effects
| 18
7
Dosing
| 19
Possible Unique Pathogen Opportunities
• Avibactam restored activity of ceftazidime in ceftazidime
non-susceptible bacteria in animal infection (thigh,
pyelonephritis, systemic infection induced by
intraperitoneal injection) models caused by
• Ceftazidime resistant carbapenemase, ESBL, and ampC
producing Enterobacteriaceae (CRE)
• Alternative to colistin or tigecycline for many CRE / KPC
infections
| 20
Utilization and Questions for the Future
Only limited clinical safety and efficacy data is available, so
reserve Avycaz for use in patients who have limited or no
alternative treatment options in infections that are proven
or strongly suspected to be caused by susceptible
bacteria
Data for pneumonia or other common infections?
Data for pediatrics?
| 21
8
Costs
| 22
We will get to it later.
Teaching Old Dogs New Tricks
Combining old products with new medications
| 23
Ceftolozane / tazobactam
• Indications
• Complicated intra-abdominal infections: in adults, IN
COMBINATION with metronidazole, caused by Enterobacter
cloacae, Escherichia coli, Klebsiella oxytoca, K. pneumonia,
Proteus mirabilis, Pseduomonas aeruginosa, Bacteroides
fragilis, Streptococcus anginosus, Streptococcus constellatus,
and Streptococcus salivarius.
• Urinary tract infections: Treatment of complicated urinary tract
infections, including pyelonephritis, in adults caused by
Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, and
Pseudomonas aeruginosa
| 24
9
Clinical Data
cIAI
• 979 adults (Mostly community acquired infections)
• Ceftolozane/tazobactam plus metronidazole or meropenem plus
placebo for 4-10 days
• CrCl<15 excluded and CrCl <30 withdrawn
| 25
Analysis
Population
Cetolozane/tazobactam
Plus metronidazole
n/N (%)
Meropenem
n/N (%)
Treatment Difference
(95% CI)€
MITT (Microbiological intent to treat) 323/389 (83) 364/417 (87.3) 14.3 (-9.2, 0.7)
ME (Microbiologically evaluable) 259/275 (94.2) 304/321 (94.7) -0.5 (-4.5, 3.2)
Deaths 2.3% (11/482) 1.6% (8/497) (Not considered drug related)
Non-inferior outcomes met for both endpoints
Sub group Analysis
Reduced efficacy for:• Age ≥ 65
• APACHE Score >10
• CrCl 30 ≤ 50 ml/min
• Poly-microbial infections
| 26
MITT Subgroup of Primary
Efficacy Outcome
Ceftolozane/tazobactam
plus Metronidazole
Meropenem Difference
Age >= 65 68/100 (69%) 70/85 (82%) -13
APACHE Score > 10 54/78 (69%) 56/70 (80%) -11
CrCL <50 mls/min 11/23 (47%) 9/13 (69%) -22
Clinical Data
cUTI
• 1083 adults with cUTI
• Zerbaxa or levofloxacin with placebo controls in each group
• Complete resolution or marked improvement and microbiological
eradication at the test of cure visit
| 27
Analysis Population Ceftolozane/tazobactamn/N (%)
Levofloxacinn/M (%)
Treatment Difference (95% CI)
mMITT 306/398 (76.9) 275/402 (68.4) 8.5 (2.3, 14.6)
LevofloxacinResistant baseline
pathogens(s)
60/100 (60) 44/112 (39.3)
No levofloxacinResistant baseline
pathogens(s)
246/298 (82.6) 231/290 (79.7)
ME 284/341 (83.3) 266/353 (75.4) 8.0 (2.0, 14.0)
Conclusion of superiority in general population driven by levofloxacin resistant group,
including ESBL population
10
Sub Group Analysis
Unlike the cIAI population, there were no significant
differences in efficacy in older patients but there was a
trend toward reduced efficacy
There were no differences in responses by geographic
regions, sex or race.
There was a trend toward reduced efficacy in patients with
CrCl 30 - ≤50 ml/min
| 28
Dosing in Patients at least 18 years
Intra-abdominal infections (complicated):
• IV: 1.5 g (infused over 1 hour) every 8 hours for 4 to 14
days in combination with metronidazole
Urinary tract infections (complicated, includes
pyelonephritis):
• IV: 1.5 g (infused over 1 hour) every 8 hours for 7 days
| 29
Estimated CrCl (mls/min) Recommended Dosage Regimen
>50 mls/min 1.5 g IV every 8 hours
30 to 50 mls/min 750 mg IV every 8 hours
15 to 29 mls/min 375 mg IV every 8 hours
<15ml/min NOT on dialysis There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied)
ESRD on hemodialysis Initial: 750 mg for one dose, followed by 150 mg every 8 hours. Administer dose immediately after dialysis on dialysis days
Potential Opportunities / Gaps in Coverage
• One of the most potent agents against pseudomonas on the market
today
• Stable against AmpC hydrolysis
• Not a substrate for active efflux allowing activity to remain
against strains resistant to carbapenems or other cephalosporins
• Enhanced activity against many MDR E.Coli
• May have activity against some resistant Acinetobacter baumannii
• Not as reliable for ESBL Enterobacteriaceae
• Unreliable anaerobic coverage so metronidazole is needed when
anaerobes must be covered
• Poor gram positive coverage (Lacks Staph coverage)
• Off label indications like pneumonia? Pediatrics ?
| 30
11
Costs
| 31
Regimen Dose Frequency Cost/day
Meropenem 1gm q8h $25.80
Piperacillin/
Tazobactam
4.5gm q8h $27.81
Cefepime 2gm Q8h $38.91
Ceftazidime/
Avibactam
2.5gm Q8h $798
Ceftolozane/
tazobactam
1.5gm q8h $249
Lets Stay Positive: New Gram Positive
Antimicrobials
| 32
| 33
Indications:
Acute bacterial skin and skin structure infections (ABSSSI) caused by
susceptible isolates of the following gram-positive microorganisms:
•Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-
susceptible [MSSA] isolates),
•Streptococcus pyogenes
•Streptococcus agalactiae
•Streptococcus anginosus group
•Enterococccus faecalis (including VRE)
12
Clinical Data
ESTABLISH-1
• Tedizolid 200mg daily x 6 days vs. linezolid 600 bid x 10
days for ABSSSI (cellulitis, major abcess, wound
infection with node involvement or fever
• 667 patients
• Primary efficacy:
• Early clinical response at 48-72hr assessment defined as
cessation/reduction of spread of redness, edema and/or
induration of lesion AND resolution or absence of fever.
• Secondary efficacy:
• Sustained clinical response at end of treatment (day 6 tedizolid
and day 10 linezolid) and also post-therapy evaluation visit day
7-14 days after end of treatment.| 34
Results of ETABLISH-1
Authors concluded based on results that tedizolid was a
statistically non- inferior treatment to linezolid in early
clinical response at 48 to 72 hours after initiating therapy
for an ABSSSI.
| 35
ESTABLISH-2 (Is oral step down acceptable?)
• Included patients ≥ 12 years old non-inferior IV to oral
tep-down therapy
• 666 patients
• Conclusions:
• Authors concluded based on results that Intravenous to oral
once-daily tedizolid 200 mg for 6 days was non-inferior to twice-
daily linezolid 600 mg for 10 days for treatment of patients with
acute bacterial skin and skin-structure infections.
• Safety:
• GI events less with tedezolid (16% vs. 20%)
• Not
| 36
13
Safety
• Safety:
• GI events less with tedezolid (16% vs. 20%)
• Neutropenia: Not recommended in patients with ANC<1000
• Thrombocytopenia (2%)
| 37
Dose
200mg IV/PO daily for 6 days
No dosage adjustment necessary in renal or hepatic
impairment
| 38
Unique Features / Further Questions
• Once a day dosing approved for shorter course (6 days)
• Little risk of serotonin agent interactions unlike linezolid
• May be an option where SSRI, SNRI can not be stopped
• Further questions:
• Pediatrics?
• Indications other than ABSSSI?
• Linezolid has CAP / HCAP indications
| 39
14
Costs
Medication Cost/day Cost/Treatment Course
Tedizolid 200mg tablet $220 $1320*
Linezolid 600mg tablet $140.18 $1401
Tedizolid 200mg IV $219 $1314**
Linezolid 600mg IV $81.82 $818**
| 40
*200mg IV/PO daily for 6 days
**600mg IV/PO bid for 10 days
Acute bacterial skin and skin structure infections
• Staphylococcus aureus (MRSA, MSSA)
• Streptococcus pyogenes
• Streptococcus agalactiae
• Streptococcus dysgalactiae,
• Streptococcus anginosus group (including S. anginosus,
S. intermedius, S. constellatus)
• Enterococcus faecalis (vancomycin-susceptible isolates
only)*
*Enterococcus is formally included in oritavancin indications but not
dalbavancin
| 41
Clinical Data
DISCOVER1 and DISCOVER 2 - ABSSI
• Dalbavancin vs. Vancomcin x 3 days to PO linezolid for
10-14 day course (age 16-93)
• Non-inferior
• All MRSA had MIC of 1 or less to vancomcyin
• Less total adverse effects in dalbavancin(32.8% vs. 37.9%)
• Less pruritus and diarrhea
• More ALT elevations 12 (0.8%) vs. 2 (0.2%)
• Most common (Nausea 5.5%, Headache 4.7%, Diarrhea 4.4%)
| 42
15
Dosing
Half life is 8.5 days from a single dose
2 dose regimen (CrCl>30 and dialysis):
• 1000mg IV over 30 minutes followed by 500mg IV 7
days after the first dose is given
CrCl<30 and not receiving dialysis
• 750mg IV once followed by 375mg 1 week later
| 43
Clinical Opportunities and Questions
• Indications other than ABSSSI?
• Pediatrics?
• What if patient does not respond?
• Might be a good outpatient option in patients needing IV
antibiotics
• Mitigates need for prolonged IV access and possibly a hospital
admission
• Easy dosing (No levels)
| 44
Clinical Data
SOLO 1 and 2
• Oritavancin once vs. Vancomycin for 7-10 days
• Vancomycin MIC >2 excluded
• Diabetic foot infections excluded
• Mean vancomycin trough level = 15.4
• Non-inferior
• Adverse effects
• Flase elevation in aPTT for 48 hours and INR for 24 hours
• Use if IV Heparin “contraindicated” for 48 hours
• N/V/D
• ALT/AST elevations
• Increases exposure to warfarin potentially increasing bleeding risk
• More cases of osteomyelitis in Phase 3 – alternative tx if osteomyelitis
present or develops
| 45
16
Dosing
1200mg IV D5W over 3 hours once
• Mean half life is 10.2 days
• Not removed by dialysis
• No adjustments for mild-moderate renal impairment
• No studies in patients with severe renal impairment
| 46
Clinical Opportunities and Questions
| 47
• Requires a 3 hour infusion but a reasonable 1 dose option for ambulatory
patients
• In vitro activity against VRSA and VRE
• Pediatrics
• Other indications?
• Osteomyelitis warning?
Costs and Summary Table
Name IV/
PO
Infusio
n time
(hrs)
Frequen
cy
Duratio
n of
therapy
Drug
Interactions
Lab
interactions
Cost per
treatment
course
Cost per
unit
Dalbavancin IV 0.5 Once a
week x 2
doses
10-14
days
NONE NONE $4470 $1490 per
500 mg vial
Oritavancin IV 3 Once 7-10
days
Weak/moder
ate CYP3A4
inducer and
weak
CYP2C19
inhibitor
False
elevation of
aPTT for 48
hours and
INR for 24
hours after
administration
$2745.17 $915.05
Tedizolid IV/
PO
1 Once a
day
6 days Tedizolid
phosphate:
no MAOI
inhibition.] **
NONE $1410 $235 per
tablet or vial
Linezolid IV/
PO
1 Twice a
day
5-14
days *
SSRI, SNRI,
TCA, MAOI,
serotonergic
agents
NONE $1183.70
for po;
$1296.90
for IV (10
days)
$118.37 per
table;
$129.69 for
IV
Vancomycin IV 1-3 Once a
day to
three
times a
day
5-14
days *
Aminoglycosi
des, NSAIDS,
other
nephrotoxins,
loop diuretics
NONE $58.08
(7-10
days)
$2.90 per vial
| 48
17
Finally!
| 49
1
Topics in Tropics
Ali Z. Chittalia, M.D., MHA.
“The good physician treats
the disease; the great
physician treats the patient
who has the disease”
William Osler
2
Microcytic Anemia (MCV<80)
Iron deficiency anemia
Thalassemia
Pb Poisoning
Sideroblastic anemia (High Iron Levels)
Anemia of inflammation (High Ferritin)
Symptoms – Fe Deficiency
Fatigue
Lack of sense of well-being
Irritability
Decreased Exercise Tolerance
Headaches …………….before symptoms of overt anemia
Advance Iron deficiency- PICA
Signs –Fe Deficiency
Facial pallor, Glossitis, Stomatitis and in particular Conjunctival pallor
Severe – Spooning of nail
3
Iron deficiency anemia
Low Hepcidin levels
Low Serum Iron, Elevated RDW
Low Ferritin ( If Ferritin >100, Fe deficiency is ruled out)
Low percentage saturation
Elevated TIBC
Reticulocyte count is very important for hemolysis
Most sensitive essay Transferrin Receptor Index (>2)
PS- Pencil or cigar shaped cells
Always look for a cause!
Prescribe supplemental iron in patients with restless leg syndrome having ferritin
<50ng/ml
Thalassemia
High RBC count
Normal Iron Studies
Thalassemia patients can develop pigmented gallstones.
Beta thalassemia can have iron overload even without transfusions
Anemia of Inflamation
Can happen with 2 weeks of Inflamation
RBC cannot use Fe from RE stores
Ferroportin Internalized
RA, Lupus, Endocarditis
Iron filled in macrophages in Bone Marrow
Treat the Cause!
4
Microcytosis
Iron-deficiency anemia, Alpha-Thalassemia trait and Beta
Thalassemia trait.
If RDW is elevated, it is Iron-deficiency.
If RDW is normal and hemoglobin electrophoresis is normal, it is
alpha-thalassemia trait.
Alpha-thalassemia trait cannot be diagnosed by hemoglobin
electrophoresis, it needs DNA analysis
Question
A young presents to the clinic for a regular checkup
CBC suggests hemoglobin no 12.2, MCV is 66
PS shows hypochromic microcytic cells and some target cells
How do you establish the diagnosis?
Pearls
Post bariatric surgery fracture, think vitamin-D deficiency
Patients with bicuspid aortic valve need to be evaluated for dilation
of the aortic arch
AAA: Repair if>5.5 cm or growth greater than 0.5cm /yr, 4 to 5.4 cm
= follow up ultrasound every 6 months.
In patients for 80 years of age, treat only if systolic blood
pressure>150
5
Shoulder Pain
Bicipital Tendinopathy
Rotator Cuff Tendinopathy
Rotator Cuff Tear
Sub acromial Bursitis
Acromioclavicular Arthritis
Adhesive Capsulitis
Gleno humoral Osteoarthritis
Milwaukee Syndrome
6
Bicipital Tendinopathy
Pain on Abduction on Medial Side
Tenderness over the Bicipital Groove
Rotator Cuff Tendinopathy
Pain –Combing hair, Raising pants or Lifting weights above head, washing back while showering.
Pain on the lateral shoulder, laying down specially at night. Painful abduction beyond 40° and Internal Rotation.
Rotator Cuff Tear Can shrug shoulder, cannot abduct arm and cannot keep arm up after passive
intervention to 90 decrease (Drop Arm test). Mild narrowing of sub acromial
space on x-ray.
7
Rotator Cuff Tears
Physical Therapy
Injections
Medications for Pain Control
Due to risk of further tearing and risk of developing DJD from the
Cuff tear – Recommend Surgery for patients under 60.
Sub acromial Bursitis
Shoulder pain on abduction but extremes of movement are painless.
( pain 60 – 120 degree rotation)------Baseball Pitchers
Pain more on active abduction, swinging arm back and forth usually without
pain.
8
AC Joint Arthritis Pain and grinding or popping sensation while trying to put the seatbelt on
Pain on abduction beyond 120 degrees
Adhesive Capsulitis Past history of injury, arm in a cast
Stiffness, inability to move the shoulder
Pain and tenderness around the shoulder, loss of both active and passive range
of motion. X-ray maybe normal
9
Adhesive Capsulitis – “Frozen Shoulder”
Physical Therapy for ROM and stretching only!
Can take 12-18 months to resolve
Cortisone injection to relieve pain.
NSAIDs
Gleno humeral Arthritis
Glen humeral Arthritis
Gradual Onset
Progressive
Abduction and External rotation can have crepitus and tenderness
over the shoulder
DEXA can be falsely low in patients with advance OA
10
Milwaukee shoulder Difficulty with abduction, can have a joint effusion
x-ray shows calcification of ligaments. Bloody tap. Calcium phosphate crystals
and occasional Hydroxyapatite crystals.
Pearls
Pulse oximetry is normal in carbon monoxide poisoning as well as in
cyanide poisoning.
Nocturnal hypoglycemia and nocturnal hypoxia can present as
morning headaches.
Iodine contrast can mess up Thyroid function testing.
False-negative H-pylori testing is seen with patients on antibiotics,
taking Bismuth compounds or PPI. Stop for 2 weeks before doing H-
pylori testing.
Tomoxifen and estrogen can cause NASH. NASH is diagnosed by
liver biopsy not ultrasound. Goal should be to lower 15% of the body
weight.
Statistics
Null Hypothesis (P-value)
Type I and Type II Errors
Sensitivity --- Rule Out
Specificity --- Rule In
Positive Predictive Value
Negative Predictive Value
Odds Ratio
Relative Risk
Absolute Risk
NNT
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Null Hypothesis
It means the results of the study was random or by chance and not
by design.
P-Value :
Expresses statistical significance
P-Value <0.05 = statistical significance
If the P-Value is < 0.01, it needs that there is only 1% chance that the study results are fluke
Errors
Type I Error:
Investigator declares benefit when there is none.
(False Positive)
Type II Error………Beta Error
Investigator fails to declare a difference when there is one.
(False Negative)
Type II Error = BAD MISTAKE
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Sensitivity
Tells us how many have the disease
Best test to rule out disease
High Sensitivity = Low False Negatives
Specificity
How many do not have the disease
Best indicator to “Rule In” a disease or Diagnose
High Specificity = Low False Positive
Positive Predictive Value
The chance when we say they have the disease ……….they truly have the disease
Only deals with the population that tests positive
PPV increases if we have less false positive
If Specificity increases then PPV increases
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Negative Predictive Value
The chance when we say they do not have the disease ……….they truly do not have the disease
Only deals with the population that tests negative
NPV increases if we have less false negative
If Sensitivity increases then NPV increases
Statistics
RRR : Incidence in exposed/ Incidence in unexposed individuals.
ARR: Reflects the additional risk when exposed to a risk factor
Odd Ratio: Compares a population exposed to a risk developing a
disease v/s population not exposed to the risk and developing the
same disease
NNT = 1/ARR
Pearls
Always check TSH levels while evaluating myopathy, CK levels can
be elevated years before clinical symptoms of hypothyroidism
appear.
RF has 80% sensitivity and 87% specificity, anti CCP has 76% sensitivity
and 90% specificity. If it looks like RA, purse additional w/up and do
not get fooled by a negative rheumatoid factor.
Obstructive sleep apnea increases the risk of diabetes and cellulitis
of legs
In COPD patients, if getting over a 6 exacerbations per year - Every
2 months use 5 day course of rotating antibiotics.
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Pearls
Cognitive behavioral therapy and SSRIs are first-line treatment for
panic disorder. If Needed, okay to use long-acting
benzodiazepines. Do not use Xanax for panic disorder
To prevent constipation and narcotic use, use a stimulant laxative
and stool softener. Itching be is a side effect of morphine or other
narcotics, does not have to be an allergy.