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First step into insulin therapy. (How to start insulin in a patient not controlled on OADs). By. Dr.Muhammad Tahir Chaudhry. B.Sc.M.B;B.S(Pb).C.diabetology(USA). The breakthrough: Toronto 1921 – Banting & Best. Normal physiologic patterns of glucose and insulin secretion in our body.

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slide1

First step into insulin therapy

(How to start insulin in a patient not controlled on OADs)

By

Dr.Muhammad Tahir Chaudhry

B.Sc.M.B;B.S(Pb).C.diabetology(USA)

slide7

The rapid early rise of insulin secretion in response to a meal is critical,

  • because
  • it ensures the prompt inhibition of endogenous glucose production by the liver
  • disposal of the mealtime carbohydrate load, thus limiting postprandial glucose excursions.
basal insulins
Basal insulins

NPH

  • Humulin N (Eli Lilly)
  • Insulatard (Novo)

(also available as insulatard Novolet pen)

  • Dongsulin N (Highnoon)
  • Insuget N (Getz)

===========================================

Analogs

Glargine (Lantus)

Lantus Solostar Pen (Sanofi Aventis)

Detemir (Levimir) by Novo

basal insulins11
Basal Insulins

The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.

bolous insulins mealtime or prandial
Bolous insulins (Mealtime or prandial)

Human Regular

  • Humulin R (Eli Lilly)
  • Actrapid (Novo)

(Also available as Actrapid novolet pen)

  • Dongsulin R (Highnoon)
  • Insuget R (Getz)

==========================================

Analogs

  • Lispro (Humolog) by Eli Lilly
  • Novorapid by Novo
  • Aspart
  • Glulisine (Apidra) by Sanofi Aventis
bolous insulins mealtime or prandial13
Bolous insulins (Mealtime or prandial)

The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.

slide14
Pre mixed

70/30 (70% N,30% R)

  • Humulin 70/30 (Eli Lilly)
  • Mixtard 30 (Novo)

(Also available as Mixtard 30 Novolet Pen)

  • Dongsulin 70/30 (Highnoon)
  • Insuget 70/30 (Getz)

===================================

Analogs

  • Novomix 30 (Novo)
  • Humolog Mix 25(Lilly)
  • Humolog Mix 50(Lilly)
types of insulin
Types of Insulin

1. Rapid-acting

2. Short-acting

3. Intermediate-acting

4. Premixed

5. Long-acting

6. Extended long-acting

(Analogs)

(Regular)

(NPH)

(70/30)

(Lantus)

slide17

Indications for Insulin Use in Type 2 Diabetes

Pregnancy (preferably prior to pregnancy)

Acute illness requiring hospitalization

Perioperative/intensive care unit setting

Postmyocardial infarction

High-dose glucocorticoid therapy

Inability to tolerate or contraindication to oral antiglycemic agents

Newly diagnosed type 2 diabetes with significantly elevated bloodglucose levels (pts with severe symptoms or DKA)

Patient no longer achieving therapeutic goals on combination antiglycemic therapy

slide18

Proposed Algorithm of therapy for Type 2 Diabetes

Inadequate

Non pharmacological

therapy

  • Severe symptoms
  • Severe hyperglycaemia
  • Ketosis
  • pregnancy

2 oral

agents

3 oral

agents

1oral agent

Add Insulin Earlier in the Algorithm

what we have in our pockets
What we have in our pockets?
  • Basal Insulins (NPH,Lantus)
  • Bolus Insulins(Human Regular)
  • Premixed (Human 70/30)
slide21

The ADA Recommendations

on the Use of

Insulin

in Type 2 Diabetes

touch pad question
Touch Pad Question

Currently, roughly ____ of my patients with type 2 diabetes are taking some form of insulin.

1. >80%

2. 60-80%

3. 40-60%

4. 20-40%

5. 0-20%

touch pad question23
Touch Pad Question

When it comes to first-line insulin, I tend to prescribe:

1. An intermediate-acting insulin with fast-acting insulin as needed

2. A long-acting or extended long-acting insulin with fast-acting insulin as needed

3.A premixed insulin

advantages of insulin therapy
Advantages of Insulin Therapy

Oldest of the currently available medications, has the most clinical experience

Most effective of the diabetes medications in lowering glycemia

Can decrease any level of elevated HbA1c

No maximum dose of insulin beyond which a therapeutic effect will not occur

Beneficial effects on triglyceride and HDL cholesterol levels

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

disadvantages of insulin therapy
Disadvantages of Insulin Therapy

Weight gain ~ 2-4 kg

May adversely affect cardiovascular health

Hypoglycemia

However, rates of severe hypoglycemia in patients with type 2 diabetes are low…

Type 1 DM: 61 events per 100 patient-years

Type 2 DM: 1-3 events per 100 patient-years

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

balancing good glycemic control with a low risk of hypoglycemia
Balancing Good Glycemic Control with a Low Risk of Hypoglycemia…

Glycemic control

Hypoglycemia

rates of hypoglycemia for premixed vs long acting insulin oad
Rates of Hypoglycemia for Premixed vs. Long-Acting Insulin + OAD

Mean number of confirmed hypoglycemic events

per patient-year in a 28-week study

6

p=0.0009

5.73

Premixed insulin

Insulin glargine + OADs

5

4

Events per patient-year

3

2.62

2

p=0.0449

p=0.0702

1

1.04

0.05

0.00

0.51

0

Symptomatic

Nocturnal

Severe

Adapted from Janka et al. Diabetes Care 2005;28:254-9.

rates of hypoglycemia for premixed vs long acting insulin oad in elderly patients
Rates of Hypoglycemia for Premixed vs. Long-Acting Insulin + OAD in Elderly Patients

12

Rate of event per patient-year

Premixed (n=63)

Glargine + OAD (n=69)

p=0.01

10

p=0.008

8

6

p=0.06

4

2

0

All episodes of

hypoglycemia

All confirmed

episodes of

hypoglycemia

Confirmed

symptomatic

hypoglycemia

Adapted from Janka HU et al. J Am Geriatr Soc 2007;55(2):182-8.

the ada treatment algorithm for the initiation and adjustment of insulin

The ADA Treatment Algorithm for the Initiation and Adjustment of Insulin

initiating and adjusting insulin
Initiating and Adjusting Insulin

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c≤7%...

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range:add rapid-acting insulin at dinner

If HbA1c7%...

If HbA1c≤7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Target range:

3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c7%...

If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection

(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Continue regimen; check HbA1c every 3 months

Continue regimen; check HbA1c every 3 months

Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

step one
Step One…

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c≤7%...

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range:add rapid-acting insulin at dinner

If HbA1c7%...

If HbA1c≤7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Target range:

3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c7%...

If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection

(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Continue regimen; check HbA1c every 3 months

Continue regimen; check HbA1c every 3 months

Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

step one initiating insulin
Step One: Initiating Insulin

Start with either…

Bedtime intermediate-acting insulin or

Bedtime or morning long-acting insulin

Insulin regimens should be designed taking lifestyle and meal schedules into account

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

step one initiating insulin cont d
Step One: Initiating Insulin, cont’d

Check fasting glucose and increase dose until in target range

Target range: 3.89-7.22 mmol/l (70-130 mg/dl)

Typical dose increase is 2 units every 3 days, but if fasting glucose >10 mmol/l (>180 mg/dl), can increase by large increments (e.g., 4 units every 3 days)

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

step one initiating insulin cont d34
If hypoglycemia occurs or if fasting glucose < 3.89 mmol/l (70 mg/dl)…

Reduce bedtime dose by ≥4 units or 10% if dose >60 units

Step One: Initiating Insulin, cont’d

Reduction in overnight and fasting glucose levels achieved by adding basal insulin may be sufficient to reduce postprandial elevations in glucose during the day and facilitate the achievement of target A1C concentrations.

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

While using basal insulin alone,never stop or reduce ongoing oral therapy

after 2 3 months
If HbA1c is <7%...

Continue regimen and check HbA1c every 3 months

If HbA1c is ≥7%...

Move to Step Two…

After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

slide36

With the addition of basal insulin and titration to target FBG levels, only about 60% of patients with type 2 diabetes are able to achieve A1C goals < 7%.[36] In the remaining patients with A1C levels above goal regardless of adequate fasting glucose levels, postprandial blood glucose levels are likely elevated.

step two
Step Two…

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c≤7%...

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range:add rapid-acting insulin at dinner

If HbA1c7%...

If HbA1c≤7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Target range:

3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c7%...

If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection

(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Continue regimen; check HbA1c every 3 months

Continue regimen; check HbA1c every 3 months

Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

step two intensifying insulin
Step Two: Intensifying Insulin

If fasting blood glucose levels are in target range but HbA1c ≥7%, check blood glucose before lunch, dinner, and bed and add a second injection:

If pre-lunch blood glucose is out of range,

add rapid-acting insulin at breakfast

If pre-dinnerblood glucose is out of range,

add NPH insulin at breakfast or rapid-acting insulin at lunch

If pre-bed blood glucose is out of range,

add rapid-acting insulin at dinner

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

making adjustments
Making Adjustments

Can usually begin with ~4 units and adjust by 2 units every 3 days until blood glucose is in range

When number of insulin Injections increase from 1-2………..Stop or taper of insulin secretagogues (sulfonylureas).

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

after 2 3 months41
If HbA1c is <7%...

Continue regimen and check HbA1c every 3 months

If HbA1c is ≥7%...

Move to Step Three…

After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

step three
Step Three…

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin

(initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c≤7%...

Pre-lunch BG out of range: add rapid-acting insulin at breakfast

Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range:add rapid-acting insulin at dinner

If HbA1c7%...

If HbA1c≤7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):

Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Target range:

3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c7%...

If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection

(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Continue regimen; check HbA1c every 3 months

Continue regimen; check HbA1c every 3 months

Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

step three further intensifying insulin
Step Three: Further Intensifying Insulin

Recheck pre-meal blood glucose and if out of range, may need to add a third injection

If HbA1c is still ≥ 7%

Check 2-hr postprandial levels

Adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

premixed insulin
Premixed Insulin

Not recommended during dose adjustment

Can be used before breakfast and/or dinner if the proportion of rapid- and intermediate-acting insulin is similar to the fixed proportions available

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

key take home messages
Key Take-Home Messages

Insulin is the oldest, most studied, and most effective antihyperglycemic agent, but can cause weight gain (2-4 kg) and hypoglycemia

Insulin analogues with longer, non-peaking profiles may decrease the risk of hypoglycemia compared with NPH insulin

Premixed insulin is not recommended during dose adjustment

key take home messages cont d
Key Take-Home Messages, cont’d

When initiating insulin, start with bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin

After 2-3 months, if FBG levels are in target range but HbA1c ≥7%, check BG before lunch, dinner, and bed,and, depending on the results, add 2nd injection (stop sulfonylureas here)

After 2-3 months, if pre-meal BG out of range, may need to add a 3rd injection; if HbA1c is still ≥7% check 2-hr postprandial levels and adjust preprandial rapid-acting insulin.

slide48

First calculate total daily dose of insulin

Body weight in kgs / 2

  • e.g; an 80 kg person will require roughly about

40 units / day.

slide49

Dose calculation……..contd

Split the total calculated dose into 4 (four) equal s/c injections.

  • ¼ of total dose as regular insulin s/c half-hour ( ½ hr ) before the three main meals with 6 hrs gap in between.
  • ¼ total calculated dose as NPH insulin s/c at 11:00 p.m. with no food to follow.
slide50

Dose calculation: example

For example in an 80-kg diabetic requiring 40 units per day, start with:

  • 08:00 a.m. --- 10 units regular insulin s/c ½ hr before breakfast.
  • 02:00 p.m. --- 10 units regular insulin s/c ½ hr before lunch.
  • 08:00 p.m. --- 10 units regular insulin s/c ½ hr before dinner.
  • 11:00 p.m. --- 10 units NPH/ lantus insulin s/c
slide51

Dose adjustment

  • For adjustment of dosage, check fasting blood sugar the next day and adjust the dose of night time NPH Insulin accordingly i.e. keep on increasing the dose of NPH by approximately 2 units daily until you achieve a normal fasting blood glucose level of 80-110 mg/dl.
slide52

Control BSF by adjusting

the prior the dose of NPH

slide53

Dose adjustment…contd.

  • Once the fasting blood glucose has been controlled, check 6-Point blood sugar as follows:
    • Fasting.
    • 2 hours after breakfast.
    • Before lunch (and noon insulin)
    • 2 hours after lunch.
    • Before dinner (AND EVENING INSULIN)
    • 2 hours after dinner
slide55

Dose adjustment…contd.

  • Now control any raised random reading by adjusting the dose of previously administered regular insulin.
  • For example: a high post lunch reading will NOT be controlled by increasing the dose of next insulin (as in sliding scale), rather adjustment of the pre-lunch regular insulin on the next day will bring down raised reading to the required levels.
slide56

Examples

  • We need to increase the dose of NPH at night to bring down baseline sugar level (BSF) to around 100 mg/dl after which the profile should automatically adjust as follows:
    • Blood sugar fasting = 100 mg/dl
    • Blood sugar 02 hrs after breakfast = 170 mg/dl
    • Blood sugar pre-lunch = 110 mg/dl
    • Blood sugar 2 hrs. after lunch = 190 mg/dl
    • Blood sugar pre-dinner = 120 mg/dl
    • Blood sugar 2 hrs. post dinner = 180 mg/dl
  • For the following profile:
    • Blood sugar fasting = 180 mg/dl
    • Blood sugar after breakfast = 250 mg/dl.
    • Blood sugar pre lunch = 190 mg/dl
    • Blood sugar post lunch 270 = mg/dl
    • Blood sugar pre dinner = 200 mg/dl
    • Blood sugar post dinner 260 = mg/dl
slide57

Examples……contd.

  • Blood sugar fasting = 130 mg/dl
  • Blood sugar after breakfast = 160 mg/dl
  • Blood sugar pre-lunch = 130 mg/dl
  • Blood sugar post lunch = 240 mg/dl
  • Blood sugar pre-dinner = 180 mg/dl
  • Blood sugar 2 hrs. post dinner = 200 mg/dl
  • This patient needs adjustment of pre-lunch regular Insulin which will bring down post lunch and pre dinner readings within normal limits.
  • 2 hrs post dinner blood sugar(200 mg/dl) will be brought down by adjusting pre dinner regular insulin.
slide58

Combinations

  • In types 2 subjects, once the blood sugar profile is normalized and the patient is not under any stress, the total daily dose (morning + noon + night + NPH at 11 p.m) may be divided into two 12 hourly injections of premixed Insulin
slide59

Examples….contd.

  • e.g-1; If a patient is stabilized on
  • 10U R + 12U R + 10U R + 12U NPH;
  • then he may be shifted to
  • 44/2 = 22 units of 70/30Insulin 12 hourly s/c ½ hr before meal.
  • e.g-2; If the adjusted Insulin is
  • 14U R+16U R+12U R+8U NPH,
  • then split the total dose:

30 U 70/30 before breakfast and 20U 70/30 before dinner to compensate for the high morning and lunch Insulin.

slide60

Combinations………contd.

  • Problem: Remember that BD dosing usually fails to cover lunch, especially if it is heavy. So:
  • Always check for post lunch hyperglycemia when using this regimen.
  • Solution:
  • Patients can be advised to take their lunch (heavier meal) at breakfast; and breakfast (lighter meal) at lunch.
  • Adding Glucobay with lunch some times provides a reasonable control.
  • An alternate combination to overcome the problem is regular insulin for morning and noon, with premixed insulin at night.
slide61

Example

  • 10U R before breakfast + 12U R before lunch + 22U 70/30 before dinner.
  • Insulin will be injected exactly 6 hrs apart as in the QID regimen.
slide62

Choice of regimens

  • R+ R+ R+ L****
  • R+ R+ R+ N ***
  • R+ R+ premixed insulin**
  • BD premixed insulins*
slide63
Regimen # 3

(Pre mixed)

slide65

For pre mixed insulins(70/30 preparations)

Step1:First calculate the total dailystarting requirementof insulin;

body weight(kg)/2

eg, For a 60kg patient,total daily dose =30 units

Step 2:Then devide this dose into 3 equal parts;

10+10+10

Step 3:Give 2 parts in the morning and 1 part in the evening;

Morning=20U Evening=10 U

slide67

You can increase or decrease the dose of pre-mixed insulin by 10 % i.e

If the patients is using,

1-10 units…………….+/- 1 unit

11-20 units……………+/- 2 units

21-30 units……………+/- 3 units

31-40 units……………+/- 4 units…………………..

slide69

Advantages:Easy to administer for the physician.Easy to fill and inject by the patient.Provides both basal and bolus coverage with fewer number of injections.

slide70

Disadvantage:No dose flexabilityIf u increase/decrease the dose of one component ,the dose of other component is also changed un desirably

slide76

Somogyi phenomenon

  • Due to
    • excess dose of night time insulin, or
    • Night insulin taken early
  • Peaks at 3:00 a.m: hypoglycemia
  • Counter regulatory hormones released in excess:
  • Resulting in over correction of hypoglycemia:
  • Fasting hyperglycemia
  • Solution:
    • Check BSL AT 3 :00 a.m
    • Give long acting at 11:00 p.m so peak comes later
    • Reduce dose of night time insulin
slide78

Dawn phenomenon

  • Growth hormone surge at dawn raises insulin requirement.
  • Night time insulin taken early, fades out before dawn.
  • Fasting hyperglycemia

Solution

  • Give long acting insulin not before 11 :00 p.m
  • May need to increase dose of night time insulin
slide85

Remember

  • Insulin
    • No miracle drug
    • Has definite indications

As delivery route follows reverse physiology:

    • Good control is achieved only if residual pancreatic function is preserved to a certain extent i-e:
    • Starting insulin on time is vital

(Concept of early insulinization)

slide86

Pearls for practice

  • Never try to control diabetes with oral hypoglycemic drugs / insulin without first ensuring strict diet control.
  • Always bring fasting sugar to normal before trying to control post prandial / random blood sugar.
  • Control any underlying infection/stressful condition vigorously.
  • Keep meal timings regular with 6 hrs between the three meals.
  • Do not inject NPH before 11 p.m.
  • Keep number of calories during the meals same from day to day. The quantity and quality of diet should be same at same timings.
  • Do not use sliding scale to calculate the dose of insulin.
  • Use proper technique to inject s/c insulin.
  • Ensure proper storage of insulin.
slide88

Problems can be avoided

  • Adherence to time table is all that is required to avoid problems:
    • Regular meals
    • Regular injections
    • Regular excercise
choosing an insulin with a lower risk of hypoglycemia
Choosing an Insulin with a Lower Risk of Hypoglycemia

Insulin analogues with longer, non-peaking profiles may decrease the risk of hypoglycemia…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

slide91

Sites of injection

  • Arms 
  • Legs 
  • Buttocks 
  • Abdomen 
slide92

Sites of injection…….contd.

  • Preferred site of injection is the abdominal wall due to
  • Easy access
    • Ample subcutaneous tissue
      • Absorption is not affected by exercise.
slide94

Technique

  • Tight skin fold
  • Spirit…. X
  • Appropriate needle size
  • 90 degree angle
  • Change site to avoid lipodystrophy
slide95

Injection technique…….contd.

  • INSTRUCTIONS:
    • Keep the needle perpendicular to skin in order to avoid variability in absorption (fig-A)
    • Insert needle upto the hilt (fig-A)
    • Distribute daily injections over a wide area to avoid lipodystrophy and other local complications (fig-B)
slide96

Storage

  • Injections: refrigerate
  • Pens: do notrefrigerate
slide97

Shelf life

  • One monthonce opened
slide98

Thank you all

For

Sparing your valuable time

&

Patient listening