1. The document discusses diabetic neuropathy, including its classification, clinical characteristics, underlying mechanisms, investigations and pharmacological treatment.
2. Key points include that diabetic neuropathy has many subtypes and involves both large and small nerve fibers. The clinical features progress from negative symptoms like loss of sensation to positive symptoms like pain. Investigations include electrodiagnostic testing and skin or nerve biopsies.
3. Treatment involves first-line options like duloxetine, pregabalin and TCAs. Polypharmacy with combinations from different classes may be considered for refractory cases. Factors like comorbidities, side effects, costs and drug interactions must be evaluated when selecting an individual's treatment plan.
This presentation looks at generalised periodic epileptiform discharges and the various disorders like Creutzfeldt Jacob disease (CJD), SSPE and metabolic encephalopathies in which it is seen. SIRPID is also discussed. Triphasic waves are described. Radermacker complexes in SSPE are described.
This presentation looks at generalised periodic epileptiform discharges and the various disorders like Creutzfeldt Jacob disease (CJD), SSPE and metabolic encephalopathies in which it is seen. SIRPID is also discussed. Triphasic waves are described. Radermacker complexes in SSPE are described.
Event Related Potentials, Cognitive Evoked Potentials. These are stimulus unrelated potentials, which depend on the patient's ability to differentiate between a rare stimulus and a common stimulus.
Event Related Potentials, Cognitive Evoked Potentials. These are stimulus unrelated potentials, which depend on the patient's ability to differentiate between a rare stimulus and a common stimulus.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. I take for granted
that you know
the basics.
What seems to be
right today may
be wrong tomorrow.
What the mind
doesn’t know the
eyes don’t see!
Oh, come with old Khayyam,
and leave the Wise to talk;
One thing is certain, that Life flies;
One thing is certain, and the Rest is Lies;
The Flower that once has blown forever dies.
Myself when young did eagerly frequent Doctor
and Saint,
and heard great Argument About it and about;
but evermore came out by the same door as in I
went.
With them the Seed of Wisdom did I sow, And with
my own hand labour'd it to grow:
And this was all the Harvest that I reap'd ---
'I came like Water and like Wind I go.'
-(Omar Khayyam 11th Century)
6. Diagnosis of polyneuropathy
3 challenges
• Clinical signs & symptoms are due to
polyneuropahy.
• Categorisation of polyneuropathy
• Etiology- history, investigations- lab,
immunological, histological, genetic.
• 25 – 30% - cause not identified.
7. Evaluation of polyneuropathy
• History
• Clinical examination.
• Electrophysiological testing –
extension of clinical examination
• Laboratory investigations.
8. Clinical characteristics
• Polyneuropathies of many different etiologies
have similar signs & symptoms.
• Though the features are common the patterns
are different.
• The clinical features result from
Lack of function – negative symptoms & signs
abnormal function – positive symptoms & signs
9. Clinical characteristics
• Clinical course – acute,
subacute
chronic progressive,
remitting and relapsing forms
• Distribution of involvement
distal Vs proximal
symmetrical Vs asymmetrical
Upper limb Vs lower limb
predominance.
10. Clinical characteristics
•Types of fiber involvement
Motor, large sensory, small
sensory, autonomic
•Inheritance – family history.
•History of exposure to toxins
and drugs, concomittant
illness.
11. Neurological manifestations
negative positive
Motor Weakness, atrophy,fatigue
reduced tone
Fasciculations,
cramps
myokymia
Reflex Hypo or areflexia _
Small fiber Decrease of pain &
temperature sensation,
Loss of visceral pain
sensation
Foot ulceration
Spontaneous dull
burning pain
hyperesthesia
parasthesia
13. Axonal Vs Demyelination(Clinical)
Demyelinating Axonal
Muscle atrophy Slight Severe
Weakness Severe Severe
Reflexes Global areflexia Knee & UL
preserved
Sensory signs Motor > sensory Significant
14. Risk factors
For Painful
neuropathy
• Hyperglycemia
• Hypertension
• Dysmetabolic
syndrome
HT+DM+IHD+DYSLIPIDEMIA
For painless
neuropathy
•Greater height
•Male gender
•Smoking
•Total abstinence
from alcohol
•High HbA1C
15. Underlying Mechanisms
Agreement not yet reached on exact causal relationship
between insulin imbalance and nerve damage.
The relative importance and inter-relationship of the
various mechanisms is the subject of ongoing research
and debate.
16. Physical manifestations
• Nerve fibres degenerate
• Blood vessels supplying the nerves are ‘grossly
diseased’
Any theory needs to account for both
18. Polyol Pathway
• Polyol = Polyhydroxy alcohols
• High blood glucose
• Nerve cell and capillary membranes have insulin-
independent glucose transport.
• High intra-cellular glucose levels
• Conversion of glucose to sorbitol in nerve cells by aldose
reductase enzyme
• Sorbitol cannot cross membranes and therefore
accumulates
19. Polyol Pathway
• Consequences of high sorbitol concentration:
• Osmotic damage to nerve cells
• reduction in nerve myoinositol
• Inhibition of nitric oxide (NO) production
• Aldose reductase competes for NADPH
• NO is vasodilator
• Increased production of free radicals
• Superoxide, hydrogen peroxide, hydroxyl
• Formed during mitochondrial respiration
• Increased oxidative stress (proteins, lipids, DNA)
21. Triose phosphates
• High intracellular glucose leads increased production
of triose phosphates
• Activation of protein kinase C (PKC) via DAG
• Damages capillaries (permeability, contractility)
• Damages nerve function
• Non-enzymic reaction with proteins & DNA
• Advanced Glycation End-products (AGEs)
• Damage to capillaries and nerve fibres
• Specific cellular AGE receptors
• Protein cross-linking
22. Natural history of diabetic
neuropathy and clinical signs
and symptoms with
pathological background.
• With increasing stage of
neuropathy, there is a
progressive loss of nerve fibers
that convey sensation.
• When the fibers undergo
degeneration or impaired
remyelination, they release
impulse of positive symptoms.
• With progression of disease,
negative symptoms of sensory
loss are increased
23. Types of painful neuropathies
Acute (< 6 months)
• Truncal neuropathy.
• cachectic neuropathy-Acute,
painful,wt.loss,poor control of
DM
• Insulin neuritis -Acute painful,
weight loss, good control of DM
• Painful 3rd cranial nerve palsy.
• Easy to treat.
Chronic(> 6 months)
• Distal symmetrical
painful sensorimotor
polyneuropathy
• Entrapment
neuropathies
• Difficult to treat.
24. Clinical features –
Distal symmetrical painful sensorimotor
polyneuropathy
• Burning, superficial pain. Hypoalgesia in
later stages.
• Defective thermal sensation.
• Impaired vasomotion
• Defective autonomic function
• Intact DTR and power till late stages.
• Progressive with increasing duration of
diabetes.
• Related to glycemic control &
complications.
25. Clinical features –
Truncal neuropathy
• Truncal polyneuropathy
• Rare
• Occur in long standing
DM
• “Bandlike” Painful
symptoms in thoracic root
distribution
• Motor involvement-
muscle herniation –
asymmetric bulge in
abdominal wall
• Truncal
radiculopathy
• Acute onset of pain
in a radicular
pattern
• Asymmetrical pain
• Patchy sensory loss
is a clue to the
diagnosis.
26. Clinical features Insulin neuritis
• Acute painful, occurs 1 month after
insulin /OHA.
• Due to rapid glycemic control.
• Nerves in these patients are under
general hypoxia and use glucose
under anaerobic conditions.
• Once glucose is normalised in blood
and nerves, glucose is no longer
available and the nerves undergo
degeneration.
27. Insulin neuritis- contd..,
•Burning pain, paraesthesia, allodynia
with nocturnal exacerbation.
•Depression is a feature.
•No weight loss.
•Sensory loss is mild. No motor signs.
•Complete resolution in 1 year.
28. Clinical features - Cachectic neuropathy
• In patients with a poor control of DM.
• Wt.loss is prominent.
• Severe burning pain- continuous or
intermittent.
• Subjective feeling of swollen limb.
• Allodynia is common- nocturnal exacerbation.
• Sensory loss is mild.
• No motor signs.
29. Cranial nerve palsy
• Most common mononeuropathy
• Acute pain in the orbit, ptosis,
opthalmoplegia, pupil spared.
• Usually unilateral
• Complete recovery in 3 months.
• Vascular etiology suggested.
• 6th & 7th cranial nerve involvement are
described.
30. Peripheral Autonomic Dysfunction
•Contributes to the following
symptoms/signs:
• Neuropathic arthropathy (Charcot foot)
• Aching, pulsation, tightness, cramping, dry
skin, pruritus, edema, sweating
abnormalities
• Weakening of the bones in the foot leading
to fractures
33. Morphology- nerve biopsy
• Nerve biopsy – invasive procedure with
definite morbidity.
• Sural nerve most commonly used.
• Routine biopsy is controversial.
• To rule out other causes like vasculitis etc.,.
• Light & electron microscopic studies are
necessary.
• Can be done pre and post treatment to
assess response
34. Section of a sural nerve from a patient with
diabetic neuropathy
35. Morphology- Skin punch biopsy
• Small nerve visualisation – assessment of
cutaneous nerve fibers obtained from 3mm
skin punch biopsy – promising in DSP.
• Immunohistochemistry- antibody to general
neuronal marker protein gene product
9.5.(PGP 9.5)
• The relationship between epidermal nerve
fibers and clinical scores is nonlinear.
• Reappearance is a marker for diffuse
peripheral nerve regeneration and recovery.
• At present not advocated for routine
evaluation
38. Bench To Bed side
• Diabetic Peripheral Neuropathy Pain refractory to initial
therapies
• Diabetic Peripheral Neuropathy Pain in the presence of
comorbidity
• Non Diabetic Neuropathy in a patient with diabetes
mellitus
• Rational Polypharmacy DPNP
39. Bench To Bed side
• Diabetic Peripheral Neuropathy Pain refractory to initial
therapies
• Diabetic Peripheral Neuropathy Pain in the presence of
comorbidity
• Non Diabetic Neuropathy in a patient with diabetes
mellitus
• Rational Polypharmacy DPNP
40. Pharmacological Treatment of
DPNP by Drug Class
Class
• SNRI ( highly specific inhibition of serotonin
and Norepinephrine reuptake)
• Alpha 2 delta ligands ( modulate voltage –
gated Calcium channels )
• TCAs( inhibit reuptake of serotonin and
Norepinephrine)
• Opioids ( block mu opiod receptors)
• Topical agents
• Agents to AVOID ( never use)
Individual agents
• Duloxetine, Venlafaxine
• Pregabalin ( Lyrica), gabapentin.
• Tertiary ( amitriptyline); secondary (
desipramine)
• Tramadol, oxycodone CR, morphine;
methadone levorphanol;hydromorphone
• Capsaicin; lidocaine
• Meperidine, propoxyphene;NSAIDs; acetaminophen, amitriptyline( for
patients > 60 years); vitamin B6 (>250 mg/d due to its potiential for
neurotoxicity) pentazocine ( due to CNS toxicity and reversal of its analgesic
effect.)
41. AEDs
Carbamazepine
1. FDA approved for Trigeminal
Neuralgia
2. Side effects
Oxcarbazepine
1. One study for NeP
2. Hyponatremia – monitoring of
serum sodium required
3. Rash – 4 %
4. Few Drug-drug interaction
Levetiracetam
1. No controlled studies
Tiagabine
1. No controlled studies
Lamotrigine
1. Rash 10%
2. 2nd-line
3. Insomnia
Topiramate
1. Negative results (3 - / 1 +)
2. Weight loss (10-20%)
3. Cognitive impairment
4. Nephrolithiasis (1.5%)
Valproate
1. Nausea
2. Sedation
3. Fatal Hepatotoxicity - Enzymes
4. Hair loss
5. Hematologic effect (Platelet)
6. Drug-drug interactions
42. Agent type Reasons for recommendation Agent name
First line > 2 RCTs in DPN Duloxetine,oxycodone CR,
pregabalin, TCAs
Second line 1 RCT in DPN; > 1 in other Carbamazepine, gabapentin
painful neuropathies lamotrigine, tramadol,
venlafaxine ER
Topical Mechanism of action Capsaicin, lidocaine
Others > RCTs in other painful Bupropion, citalopram
neuropathies or other methodone, paroxetine,
evidence phenytoin, toriramate.
Recommendation for First- and Second- Line
Agents for DPNP
43. Bench To Bed side
• Diabetic Peripheral Neuropathy Pain refractory to
initial therapies
• Diabetic Peripheral Neuropathy Pain in the presence
of comorbidity
• Non Diabetic Neuropathy in a patient with diabetes
mellitus
• Rational Polypharmacy for DPNP
44. Factors to consider in choosing First –Line Agents
Factor Recommended Avoid
Medical co-morbidities
Glaucoma
Orthostatic phenomena
Cardiac or
electrocardiographic
abnormality
Hypertension
Renal insufficiency
Hepatic insufficiency
Falls and balance issues
Any other first line agent
Any other first line agent
Any other first line agent
Any other first line agent
Any other first line agent
Any other first line agent
Any other first line agent
TCA s
TCA s
TCA s
TCA s
Duloxetine
Pregabalin,TCAs
45. Factors to consider in choosing first line agents
Factor Recommended Avoid
Psychiatric comorbidities
Depression
Anxiety
Suicidal ideation
Somatic issues
sleep
Erectile dysfunction
Other factors
Cost
Drug interactions
Weight gain
Edema
Duloxetine,TCAs
Any other first line agent
Duloxetine,Pregabalin
Any other first line agent
Second line agent
Venlafaxine
TCA s oxycodone CR
Oxycodone, Pregabalin
Duloxetine, oxycodoneCR
Any other first line agent
oxycodoneCR pregabalin
oxycodoneCR
TCAs , oxycodone CR
All first line agents
Duloxetine,Pregabalin
Duloxetine,TCAs
TCAs,Pregabalin
Pregabalin
46. Bench To Bed side
• Diabetic Peripheral Neuropathy Pain refractory to
initial therapies
• Diabetic Peripheral Neuropathy Pain in the presence
of comorbidity
• Non Diabetic Neuropathy in a patient with diabetes
mellitus
• Rational of Poly pharmacy
47. Bench To Bed side
• Diabetic Peripheral Neuropathy Pain refractory to
initial therapies
• Diabetic Peripheral Neuropathy Pain in the presence
of comorbidity
• Non Diabetic Neuropathy in a patient with diabetes
mellitus
• Rational Polypharmacy in DPNP
50. Other Agents - Topical and
Transdermal Drug Delivery Systems
Systemic activity
Applied away from painful site
Serum levels necessary
Systemic side effects
Peripheral tissue activity
Applied directly over painful site
Insignificant serum levels
Systemic side effects unlikely
Topical
(lidocaine patch 5%)
Transdermal
(fentanyl patch)
51. Based on Class I and Class II evidence,
capsaicin cream is probably effective in
lessening the pain of PDN.
Based on Class I evidence, isosorbide dinitrate
spray is probably effective for the treatment of
PDN.
53. Religion, Spirituality and Chronic Pain
• Organized religion reduced chronic
pain
• Spirituality without affiliated regular
worship attendance increased
chronic pain prevalence
• Individuals with chronic pain are
more likely to use prayer, spiritual
support for coping
54. Summary
• Diabetic neuropathic pain is a disease, not a symptom
• “Rational” polypharmacy is often necessary
• combining peripheral and central nervous system agents
enhances pain relief
• Treatment goals include:
• balancing efficacy, safety, and tolerability
• reducing baseline pain and pain exacerbations
• improving function and QOL
• New agents and new uses for existing agents offer
additional treatment options