Energy nutrient-dense formula in critically ill

Nutritional management in
critically ill infants with
growth faltering
• Dr. Vivek Maheshwari
• Ex senior resident AIIMS ,New Delhi
• Assistant professor , Rama medical college Kanpur
• (MBBS ,MD Pedia)

.
• Nutritional imbalance in critically ill infants
.
• Consequences of nutritional imbalance during critical illness
.
• Nutrition management goal
.
• Nutritional requirements during critical illness
.
• Current nutritional management approaches and their challenges
.
• Energy and nutrient dense formula (ENDF)
.
• Summary
Contents

• Nutrition during first years of life1
• Crucial for lifelong health and well-being
• Growth failure2
• More common during infancy
• Because of programmed growth rates
• Higher nutritional requirements
Figure 1: Velocity curves for weight in boys and girls
Growth velocity is high during first 2 years of life3
1. WHO. Infant and young child feeding. 2009. [online] available from: https://www.ncbi.nlm.nih.gov/books/NBK148965/pdf/Bookshelf_NBK148965.pdf accessed 24th May 2018.
2. Cooke RJ. Eur J Clin Nutr. 2010 May;64 Suppl 1:S8-S10.
3. Tanner JM et al. Arch Dis Child. 1966 Oct; 41(219): 454–471.

1. WHO. Infant and young child feeding. 2009. [online] available from: https://www.ncbi.nlm.nih.gov/books/NBK148965/pdf/Bookshelf_NBK148965.pdf accessed 24th May 2018.
2. Cooke RJ. Eur J Clin Nutr. 2010 May;64 Suppl 1:S8-S10.
• Even short periods of nutritional deprivation1
• Have lasting effects on health
• Critical periods of growth that, if missed, may not be recoverable
10 months old patient with severe PEM on
admission showing mild brain atrophy in the form
of dilated ventricles and prominent cortical sulci2
Follow-up MRI of the same patient at day 90
after nutritional treatment showing resolution
of the signs of cerebral atrophy2

Nutritional imbalance in
critically ill infants

Organic causes of growth faltering in critically ill children2,3,4
1. Prieto MB, Cid JL. Int. J. Environ. Res. Public Health 2011, 8, 4353-4366
2. Mehta NM et al JPEN J Parenter Enteral Nutr. 2013 Jul;37(4):460-81.
3. Clarke SE, Evans S, et al. J Hum Nutr Diet. 2007 Aug;20(4):329-39.
4. Krugman SD, Dubowitz H. Am Fam Physician. 2003 Sep 1;68(5):879-84
ILLNESS RELATED
MALNUTRITION
Malnutrition affects 50% of hospitalized children
and 25-70% of the critically ill children1
• Cardiac lesions
• Celiac disease
• Chronic lung disease
• Intestinal disorders requiring
surgery
• Cystic fibrosis
• Chronic lung disease
• Neurological syndromes
Nutritional imbalance in critically ill infants

1. Prieto MB, Cid JL. Int. J. Environ. Res. Public Health 2011, 8, 4353-4366
3. Sullivan PB, Goulet O. Eur J Clin Nutr. 2010 May;64 Suppl 1:S1.
Malnutrition affects 50% of hospitalized children
and 25-70% of the critically ill children1
ILLNESS RELATED
MALNUTRITION
multifactorial2
Nutritional imbalance in critically ill infants

Causes of nutritional imbalance during critical illness
Increased nutrient
requirements1 E.g. Infants with burn injuries
Catecholamine release, pain
and anxiety, tissue metabolic
demands
Prolonged hypermetabolic
stress response
Increased nutrient
losses and
malabsorption2,3
E.g. Infants with congestive
heart failure
Decreased blood flow to the
digestive organs for nutrient
absorption
Protein energy malnutrition
(PEM)
1. Sharma RK, Parashar A. Indian J Plast Surg. 2010 Sep;43(Suppl):S43-50.
2. Hubschman LE. Infant Child Adolesc Nutr. 2013 Jun;5(3):170-6.
3. Mehta NM, Corkins MR, et al. JPEN J Parenter Enteral Nutr. 2013 Jul;37(4):460-81.
4. Mehta NM, Bechard LJ, et al. Crit Care Med. 2012 Jul;40(7):2204-11.
Decreased intake4 Fluid restriction in the acute phase of
pediatric critical illness
Energy and protein deprivation

Consequences of
nutritional imbalance
during critical illness

Imbalance
between nutrient
requirement and
intake
Cumulative
deficits of energy,
protein, or
micronutrients
Negatively affect:
Functional
outcomes
Clinical
outcomes
Growth faltering
Mehta NM et al JPEN J Parenter Enteral Nutr. 2013 Jul;37(4):460-81.
Consequences of nutritional imbalance

Growth faltering – Definition #1
Early studies on growth faltering used
criteria based on attained low weight
or, sometimes, height with a cut-off
around the 3rd or 5th centile.
For example:
Infant’s weight at 1 year is 7 kg which
is < 3rd percentile weight on WHO
growth charts for boys
Growth Faltering
Growth faltering (weight less than 3rd percentile value at year 1)
Olsen EM, Petersen J, et al. Arch Dis Child. 2007 Feb;92(2):109-14

Dynamic measures of weight gain: Fall
from a normal birth weight below a
given cut-off, dropping through major
centile spaces1
1. Olsen EM, Petersen J, et al. Arch Dis Child. 2007 Feb;92(2):109-14.
Example #1:
Weight dropping across two centile lines
on WHO growth chart over 4 months
period
Growth Faltering
Growth faltering – Definition #2
Growth faltering (weight dropping across two centile lines over 4 months period)

Growth Faltering
Example #2:
Rapid weight loss over 20 days
period of an acute illness
1. Department of Health, Govt. of Australia. Growth. Community health manual. Guideline. Birth to School entry. Jan 2017. [online] available from:
https://www.pmh.health.wa.gov.au/general/CACH/docs/manual/3%20Birth%20to%20School%20Entry/3.4/3.4.2%20Growth%20faltering.pdf accessed 25th May 2018.

1. Mehta NM et al. Pediatr Crit Care Med. 2017 Jul;18(7):675-715.
2. Bechard LJ, Duggan C, et al. Crit Care Med. 2016 Aug;44(8):1530-7.
3. Mehta NM et. al., JPEN J Parenter Enteral Nutr. 2013 Jul;37(4):460-81.
4. Hulst JM, van Goudoever JB, et al. Clin Nutr. 2004 Dec;23(6):1381-9.
5. González-Cortés R, López-Herce-Cid J, et al. Med Intensiva. 2011 Oct;35(7):417-23.
6. Rytter MJ, Kolte L, et al. PLoS One. 2014 Aug 25;9(8):e105017.
Consequences of growth faltering
Short term effects
Longer period of ventilation1
Underweight was significantly associated with 1.3
fewer ventilator free days than normal weight
(95% CI −2.1 to −0.6, P =0.001)2
High risk of hospital-acquired infection1
The odds of hospital-acquired infections
were higher in underweight infants (odds ratio, 1.88;
p = 0.008) compared to normal weight infants2
Loss of lean body mass3
In critically ill infants, cumulative energy and
protein deficits were associated with declines in
SD-scores for weight and arm circumference4
Immune dysfunction3
In malnourished infants, lymphatic tissue undergoes
atrophy, and delayed-type hypersensitivity responses
are reduced6
Increased mortality1
Mortality was higher in critically ill infants (22.9%)
with longer PICU stay than in the rest of the patients
(2%) (p < 0.001)5
Longer PICU and hospital stay1
Underweight subjects had a 29% (Hazard ratio
0.71, 95% CI 0.60- 0.84, P<0.001) lower chance of
being discharged than normal weight subjects2

Consequences of growth faltering
Long term effects
1. Krugman SD, Dubowitz H. Am Fam Physician. 2003 Sep 1;68(5):879-84.
2. Black MM, Dubowitz H, et al. Pediatrics. 2007 Jul;120(1):59-69.
3. Corbett SS, Drewett RF. J Child Psychol Psychiatry. 2004 Mar;45(3):641-54.
4. Galler JR, Ramsey F. J Am Acad Child Adolesc Psychiatry. 1987 Jan;26(1):23-7.
Lower cognitive ability1
Infants with faltering growth achieved IQ scores
approximately 4.2 points lower than children with a
history of adequate growth3
Behavior problems1
School children (≤ 13 yrs) with protein energy malnutriton
in the first year of life showed delays in performing Piaget
conservation tasks compared to matched companions4
Short stature1
At age 8 years, infants with early faltering growth were
on average 6 cm shorter than those with adequate
growth in infancy (p<0.001)2

1. To provide optimal nutrition intervention for catch up growth1
• Two principles that hold true irrespective of the etiology
• All children with growth faltering need a high-calorie diet for catch-up growth &
• All children with growth faltering need close follow-up
2. One of the most important targets of nutritional support in critically ill children2
• To prevent increased protein breakdown and loss of lean body mass
• To promote tissue synthesis
1. Krugman SD, Dubowitz H. Am Fam Physician. 2003 Sep 1;68(5):879-84.
2. van Waardenburg DA, de Betue CT, et al. Clin Nutr. 2009 Jun;28(3):249-55.
Goals for treatment of growth faltering

Nutritional requirements
during critical illness

Critical illness
• Promotes an acute inflammatory response1
• Associated with increased energy demands related to stress2
2. Raju U, Choudhary S, et al. Med J Armed Forces India. 2005 Jan;61(1):45-50.
3. Poindexter B. World Rev Nutr Diet. 2014;110:228-38.
4. Carpenter A, Pencharz P, et al. J Pediatr Gastroenterol Nutr. 2015 Jan;60(1):4-10.
Nutritional requirement during critical illness
Energy requirements
Energy recommendations for infants with illness3,4
Age Healthy infants Infants with illness
0-3 months 100- 115 kcal/kg/day 120- 200 kcal/kg/day
4-6 months 95 kcal/kg/day 120- 200 kcal/kg/day
7- 12 months 95 kcal/kg/day 120- 200 kcal/kg/day

1. Joosten K, Meyer R. Eur J Clin Nutr. 2010 May;64 Suppl 1:S22-4.
2. Mehta NM, Skillman HE, et al. Pediatr Crit Care Med. 2017 Jul;18(7):675-715.
Energy requirements
ASPEN guideline suggests2
• Attentiveness to individualized energy requirements, timely initiation and attainment of energy
targets, and energy balance to prevent unintended cumulative caloric deficit or excesses.
WHO: World Health Organization; ASPEN: American Society for Parenteral and Enteral Nutrition
WHO recommendation based on target rate of weight gain1
Rate of gain (g/kg/day) Energy (kcal/kg/day)
10 126
20 167

Protein requirements
• Catabolism of body protein during critical illness1
• Due to starvation, immobility, stress, and inflammation
• Amount of protein required to optimally enhance protein accretion is higher in critically ill
infants than in healthy infants2
1. Coss-Bu JA, Hamilton-Reeves J. Nutr Clin Pract. 2017 Apr;32(1_suppl):128S-141S.
2. Mehta NM, Compher C; A.S.P.E.N. Board of Directors. JPEN J Parenter Enteral Nutr. 2009 May-Jun;33(3):260-76.
4. Carpenter A, Pencharz P, et al. J Pediatr Gastroenterol Nutr. 2015 Jan;60(1):4-10.
ASPEN: American Society for Parenteral and Enteral Nutrition
ASPEN guideline suggests2
• Estimated protein requirements for critically ill children 0–2 years: 2–3 g/kg/day
Protein recommendations for infants with illness3,4
Age Healthy infants Infants with illness
0-3 months 2.1 g/kg/day 3-4.5 g/kg/day
4-6 months 1.6 g/kg/day 3-4.5 g/kg/day
7- 12 months 1.5 g/kg/day 3-4 g/kg/day
(to max 10 g/kg/day to 1 year)

Estimating nutritional requirement during critical illness: Case #1
Hypothetical case 1:
• 9 months old baby boy with cystic fibrosis
• On admission blood pressure was 104/49 mmHg, heart rate 90 beats/min
• Weight at admission: 6 kg [Weight for age < that for 3rd centile weight (7.2 kg)]
• Energy recommendation: 150 kcal/kg/day
• Protein recommendation: 3.5 g/kg/day
• For 9 months old boy with weight 6 kg
• Energy recommended for day = 6 * 150 = 900 kcal /day
• Protein recommended for day = 6 * 3.5 = 21 g/day
2. Carpenter A, Pencharz P, et al. JPGN.2015 Jan; 60(1): 4-10.
1,2

WHO guideline suggests1
• 8.9–11.5% of energy should be supplied as protein to provide optimal catch-up
growth of lean and fat mass
Rate of gain
(g/kg/day)
Protein
(g/kg/day)
Energy
(kcal/kg/day)
Protein energy ratio
(PE %)
10 2.82 126 8.9
20 4.82 167 11.5
Table: WHO guidelines for energy and protein intake for optimal catch-up growth
WHO: World Health Organization
% Energy from Protein

• Decreased level of micronutrients during critical illness1
• Due to acute inflammation and the body’s response to physiologic stress
• Critically ill infants are at a risk of developing micronutrient deficiency1
• Adequate Supply of electrolytes and minerals2
• To meet maintenance requirements and ongoing losses particularly from GIT
• Adequate Supply of vitamins2
• To meet maintenance requirements as well as cater to losses and supervening stress
Micronutrient requirements
1. Dao DT. Nutrients. 2017 Oct 28;9(11).
2. Raju U, Choudhary S, et al. Med J Armed Forces India. 2005 Jan;61(1):45-50.

Current nutritional
management approaches
and their challenges

• By addition of glucose polymer/ MCT Oil/ Coconut oil/ Ghee (clarified butter)/ Jaggery/ Sugar
Increasing energy density of infant formula1
• E.g.: Infant formulas are reconstituted by adding 15 g of powder (instead of 13 g) to 100 ml of water
Concentrating regular infant formula to increase concentration of nutrients1
Using commercial formulations which are meant for older children (> 2 years)
1. Clarke SE, Evans S, et al. J Hum Nutr Diet. 2007 Aug;20(4):329-39
Current nutritional management approaches

3. Steel JR et al. J Hum Nutr Diet. 2013 Feb;26(1):32-7.
Challenges with current nutritional management practices
Approaches Practical challenges
Adding an extra energy to infant
formula or kitchen feeds
• Doesn’t increase all nutrients1
• Especially protein for catch up growth
• Can reduce % energy derived from protein (from 8% to 5.5%) 1
• 8.9 to 11.5% Energy from Protein is required for catch up growth2
• Risk of preparation errors1
• Increased risk of microbial contamination1
Concentrating regular infant formula • Although increases nutrient density, not sufficient for some infants with faltering
growth1
• Increases osmolality of feed3
• Can induce osmotic diarrhea
• Risk of preparation errors1
• Increased risk of microbial contamination1
Using commercial formulations which
are meant for older children (> 2 years)
• Nutrient profile not suitable for infants <2 years of age
• High osmolality
• High potential renal solute load (pRSL)
Use of kitchen diets/ blenderized foods • Nutrient delivery is not adequate as that of standard feed
• Increased risk of microbial contamination

Need for appropriate measure / formula
• Provides not only high calorie but also high protein and micronutrients1
• Do not disturb protein: energy ratio1
• Has optimum osmolality (< 400 mOsm/L or 450mOsm/kg)2,3
2. AAP. Pediatrics. 1976 Feb;57(2):278-85.
3. Balmer MA, Smith RD. JADA.1995 Sep:95(9 Suppl):A23.

Energy and Nutrient
Dense Formula (ENDF)

3. de Betue CT et al. Arch Dis Child. 2011 Sep;96(9):817-22.
4. Evans S, Twaissi H, et al. J Hum Nutr Diet. 2006 Jun;19(3):191-7; quiz 199-201
ENDF: Energy and nutrient dense formula
Role of ENDF in infants with growth failure
ENDF
Improves energy
balance2
Promotes weight
gain and linear
growth1
Improves nitrogen
balance and protein
anabolism2,3
Provides optimal %
energy from protein1
Promotes greater
intakes of all
nutrients1,2

ENDF promotes higher intakes of all nutrients
• 18 mechanically ventilated infants with respiratory failure due to RSV-bronchiolitis received
PE-formula or S-formula
• Significantly higher intakes of energy and protein on days 3, 4 and 5 in PE formula
group compared to the S-formula group (p<0.01)1*
PE formula: Protein and energy-enriched formula; S- formula: Standard formula; PE formula is same as ENDF
1. van Waardenburg DA, de Betue CT, et al. Clin Nutr. 2009 Jun;28(3):249-55
*A double-blind randomized controlled trial. 18 mechanically ventilated infants (aged 4 weeks- 12 months) admitted to the PICU with respiratory failure due to RSV bronchiolitis were randomized to continuous enteral feeding with PE-formula (n=8) or S-formula (n=10).

ENDF promotes higher intake of all nutrients
• 49 infants with faltering growth randomized to receive ENDF or ESF
• Significantly greater intakes of all nutrients in ENDF group compared to ESF group1^
• 27–42% higher intakes for protein, sodium, potassium, calcium, zinc, iron, vitamin D & C
(p<0.0001) and 14% higher intake for vitamin A ; (p=0.001)
• Median protein intakes were 3.7 g/kg/day for the ENDF group and 2.0 g/kg/day in the ESF group
ENDF: Energy and nutrient dense formula; ESF: Energy supplemented formula
^ Open parallel randomized study. 49 infants [median age of 5 weeks (range 2-31)] with growth faltering due to cardiac lesions, cystic fibrosis, or other organic causes randomized receive ENDF (n=26) or ESF (n=23) for 6 weeks.
Nutrient intake as a percentage of dietary reference values (DH 1991)
for Energy and nutrient dense formula (ENDF) and Energy Supplemented Formula
(ESF) group1

ENDF provides optimal % energy from protein
• ENDF provided 10.4% energy from protein compared to only 5.5% from the
ESF1^
• WHO recommendation for % energy from protein: 8.9-11.5%
2. Joosten K, Meyer R. Eur J Clin Nutr. 2010 May;64 Suppl 1:S22-4

1. van Waardenburg DA, de Betue CT, et al. Clin Nutr. 2009 Jun;28(3):249-55
ENDF improves energy balance
• 18 mechanically ventilated infants with respiratory failure due to RSV-bronchiolitis
received PE-formula or S-formula
• Significantly higher energy balances on day 3-5 in PE formula group
compared to S- formula group1*
Days Daily energy balances
PE- formula group S- formula group
Day 3 40±12* 15±3*
Day 4 44±9* 27±5*
Day 5 52±9* 30.9±6*
Daily energy balances
*All p<0.05

ENDF improves nitrogen balance
• Significantly higher cumulative nitrogen balance calculated over days 2–5 in PE-
formula group compared to S-formula group [(866±113) vs (297±71) (p<0.01)]1^
• Positive nitrogen balance in all PE formula infants (reflecting anabolism) by day 21^
• Negative nitrogen balance in some S formula infants (reflecting catabolism) until day 41^
*A double-blind randomized controlled trial. 18 mechanically ventilated infants (aged 4 weeks to 12 months) admitted to the PICU with respiratory failure due to RSV bronchiolitis were randomized to continuous enteral feeding with PE-formula (n=8) or S-formula (n=10).
# A double-blind randomized controlled trial. 18 infants (aged 4 weeks to 12 months) admitted to the PICU with respiratory failure due to viral bronchiolitis were randomized to continuous enteral feeding with PE-formula (n=8) or S-formula (n=10).
• 18 infants admitted to PICU with respiratory failure due to viral bronchiolitis received PE-
formula or S-formula
• Significantly higher 24 h nitrogen balance on day 5 in PE formula group compared
to S- formula group (274±127 vs 137±53 mg/kg/24 h, p<0.05)2#

• Higher sum of BCAA and all essential amino acids in PE formula group compared
to S formula group on day 5 (p<0.05, p<0.01 respectively)1*
BCAA: branched chain amino acids (isoleucine, leucine and valine); EAA: essential amino acids (methionine, histidine, phenylalanine, tryptophane, lysine, threonine and BCAA)
Parameter PE-Group S-Group P value
Sum of all EAA 1047 (±80) 817 (±42) p<0.05
Sum of BCAA 305 (±17) 251 (±9) p<0.01

• 18 mechanically ventilated infants with respiratory failure due to RSV-bronchiolitis
received PE-formula or S-formula
• Plasma levels of essential amino acids were within reference limits in PE-
formula group, whereas below these limits in S-formula group on day 5 (p<0.05) 1*
Plasma Amino Acids
(µmol/l)
PE-formula Group
S-formula
Group
Reference values
Methionine 36 (±2) 28 (±2) 30-59
Histidine 72 (±5) 58 (±4) 59-110
Valine 142 (±9) 104 (±3) 108-214
Phenylalanine 77 (±4) 64(±3) 43-87

ENDF improves protein anabolism
• 18 infants admitted to PICU with respiratory failure due to viral bronchiolitis received PE-
formula or S-formula
• Significantly higher whole body protein balance in the PE formula group compared to
S- formula group on day 5 resulting from significantly increased whole body protein synthesis1#
PE formula S-formula
Whole body protein
balance
0.73±0.5
g/kg/24 h
0.02±0.6
g/kg/24 h
Whole body protein
synthesis
9.6±4.4
g/kg/24 h
5.2±2.3
g/kg/24 h
• Higher whole body protein turnover in the PE formula group than in the S formula group
(10.7±4.3 vs 5.8±2.6 g/kg/24 h, p=0.012)1#
# A double-blind randomized controlled trial. 18 infants (aged 4 weeks to 12 months) admitted to the PICU with respiratory failure due to viral bronchiolitis were randomized to continuous enteral feeding with PE-formula (n=8) or S-formula (n=10).

ENDF promotes linear growth
• Median linear growth:1^
• ENDF group: 0.67 cm/week
• ESF group: 0.60 cm/week
• Significantly better age appropriate length maintenance in ENDF group
compared to ESF group (p<0.01)1^
• Significant decline in length z-score in the ESF group (p=0.01)1^

ENDF promotes weight gain
• Significant gain in weight from the baseline in the ENDF group (p<0.007) over 6 weeks1^
• ENDF group retained blood urea levels in the normal range while it had fallen
significantly in the ESF group (p=0.001)1^
Biochemical
parameters
ENDF ESF
P Value
Start
Median
change
Start
Median
change
Blood Urea
(mmol/L)
3.4 0.2 3 -1.4 0.001

Early administration of ENDF in critically ill infants
• Promotes a more adequate nutrient intake
• Improves energy and nitrogen balance
• Improves protein anabolism
• Promotes catch up growth
Key findings of the clinical evidence

Estimation of Nutritional requirement during critical illness:
Case #2
Hypothetical case #1:
• 4 months old baby girl with Sepsis
• Child had a fever (39 °C) for approximately six days
• Heart rate:160 beats/min
• Weight at admission: 5 kg [below 3rd centile (5.2 kg)]
• Energy recommendation: 160 kcal/kg/day
• Protein recommendation: 4 g/kg/day
• For 4 months old baby with weight 5 kg
• Energy recommended per day = 5 * 160 =800 kcal /day
• Protein recommended per day = 5 * 4 = 20 g/day
2. Carpenter A, Pencharz P, et al. JPGN.2015 Jan; 60(1): 4-10.
1,2

Estimating nutritional requirement during critical illness: Case #2
ENDF composition:
• Energy: 100 kcal/100 ml
• Protein: 2.6 g/100 ml
• As ENDF provides 100 kcal/100 ml,
therefore 800 kcal will be provided by 800
ml, therefore 800 ml/ day of ENDF need to
be prescribed
• 800 ml of ENDF will contain 20.56 g of
protein
Aim is to provide 800 kcal/day of energy and 20g/day of protein
Standard formula composition:
• Energy: 68 kcal/100 ml
• Protein: 1.4 g/100 ml
• As standard formula provides 68 kcal/100 ml,
therefore 800 kcal will be provided by 1176 ml,
therefore 1176 ml/ day of standard formula need to
be prescribed
• 1176 ml of standard formula will contain only17.52 g
of protein
Energy and nutrient dense formula (ENDF) V/S Standard Formula
• Thus, to meet energy requirements (800 kcal/day) in 4 months old baby with sepsis, 800 ml/day of ENDF vs 1176 ml/day
of standard formula will be needed
• For standard formula, despite providing higher quantity (1176 ml), meets energy requirement and not protein
requirement (17.52 g)

After Discharge now question ? How to manage
severe malnourished childs / neonate

Summary
• Malnutrition is prevalent amongst children during critical illness
• Common mechanisms for malnutrition include decreased intake, increased requirement,
excessive losses, and failure to assimilate the delivered nutrients
• Nutritional imbalance may lead to development of growth faltering and may affect in
short as well as long term
• There is increased energy, protein, and micronutrient requirements during critical illness
• ENDF may improve energy and nutrient intake, weight gain, linear growth, and protein
anabolism in these infants

Energy nutrient-dense formula in critically ill

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