Deranged biochemical and hematological profile of septicemia patients in Mayo hospital, Lahore

Abstract

Septicemia is a devastating medical condition encountered in many hospitals of developing countries. Hepatorenal dysfunction is traditionally viewed as late feature of septicemia due to its obvious effects on hepatorenal organs. This study was undertaken to establish the possible role of serum biomarkers of liver, kidney and blood in the diagnosis of septicemia. 101 confirmed patients of septicemia from a tertiary care hospital in Lahore were included. Liver and renal function tests were performed for all patients. Patients were divided into 3 age groups on the basis of age: 30-50, 51-70 and 71-90 years. In Liver function Tests, ALT (37.62%), AST (50.49%) and ALP (99%) were elevated, Bilirubin was normal in majority of patients while total protein was in normal range in 97.02% patients and the trend of albumin was towards low (44.55%).In Renal function tests, urea was elevated in 71.29% and creatinine in 51.48% patients and in electrolytes Na+ was low in 41.58% patients K+ were normal in majority of patients. Hematological parameters such as WBCs were high in 84.16%, hemoglobin was low in 78.12% and platelets were normal. The most common causes were urinary tract infection (31.68%), bed sores (17.82%), chest infection (12.87%) and wound infection (7.92%). According to this study, diabetes (45.56%) was the main comorbidity of septicemia. Most of the patients were between 51-70 years while septicemia occurred equally in both genders. Major predictors for diagnosis were WBCs, hemoglobin, AST, ALT, ALP, urea and creatinine. Other biomarkers gave no information regarding septicemia diagnosis. This demands the use of improved diagnostic biomarkers in developing countries.

Full text

Punjab Univ. J. Zool., Vol. 31 (1), pp. 087-093, 2016 ISSN 1016-1597(Print)
ISSN2313-8556 (online)
75-PUJZ-61020250/16/0087-0093 Copyright 2016, Dept. Zool., P.U., Lahore, Pakistan
*Corresponding author: mehboob.riffat@gmail.com
Original Article
Deranged biochemical and hematological profile of septicemia patients in
Mayo hospital, Lahore
Riffat Mehboob1*, Sami Ullah Mumtaz2, Zoya Manzoor3, Sajid Abaidullah2, Fridoon
Jawad Ahmad1
1Department of Biomedical sciences, King Edward Medical University, Lahore, Pakistan
2North Medical Ward, King Edward Medical University, / Mayo Hospital, Lahore, Pakistan
3Center for research in Molecular Medicine, University of Lahore, Pakistan.
(Article history: Received: May 20, 2016; Revised: June 15, 2016)
Abstract
Septicemia is a devastating medical condition encountered in many hospitals of developing countries. Hepatorenal
dysfunction is traditionally viewed as late feature of septicemia due to its obvious effects on hepatorenal organs. This
study was undertaken to establish the possible role of serum biomarkers of liver, kidney and blood in the diagnosis of
septicemia. 101 confirmed patients of septicemia from a tertiary care hospital in Lahore were included. Liver and
renal function tests were performed for all patients. Patients were divided into 3 age groups on the basis of age: 30-
50, 51-70 and 71-90 years. In Liver function Tests, ALT (37.62%), AST (50.49%) and ALP (99%) were elevated,
Bilirubin was normal in majority of patients while total protein was in normal range in 97.02% patients and the trend of
albumin was towards low (44.55%).In Renal function tests, urea was elevated in 71.29% and creatinine in 51.48%
patients and in electrolytes Na+ was low in 41.58% patients K+ were normal in majority of patients. Hematological
parameters such as WBCs were high in 84.16%, hemoglobin was low in 78.12% and platelets were normal. The most
common causes were urinary tract infection (31.68%), bed sores (17.82%), chest infection (12.87%) and wound
infection (7.92%). According to this study, diabetes (45.56%) was the main comorbidity of septicemia. Most of the
patients were between 51-70 years while septicemia occurred equally in both genders. Major predictors for diagnosis
were WBCs, hemoglobin, AST, ALT, ALP, urea and creatinine. Other biomarkers gave no information regarding
septicemia diagnosis. This demands the use of improved diagnostic biomarkers in developing countries.
Keywords: Septicemia, comorbidity, inflammatory responses, Lahore.
To cite this article: MEHBOOB, R., MUMTAZ, S.U., MANZOOR, Z., ABAIDULLAH, S. AND AHMAD, F.J., 2016.
Deranged biochemical and hematological profile of septicemia patients in Mayo hospital, Lahore. Punjab Univ. J.
Zool., 31(1): 87-93.
INTRODUCTION
epticemia is a systemic inflammatory
response caused by the circulation of
pathogenic organisms or their toxins in
the blood or tissues (Sridharan and Chamberlain
2013). Septicemia is often caused by bacterial
infection such as Staphylococcus aureus,
sometimes preceded by or occurring in
combination with viral infections and, to a lesser
extent, fungal infections (Grant, 2009). During
the past few decades, it has become an
increasingly common condition among
hospitalized patients (Dellinger, 2016). It causes
over 34,000 deaths each year in the United
States (Melvan et al., 2011). In Pakistan,
septicemia is one of the leading causes of
hospital mortality (Tariq et al., 2009). Symptoms
vary among different patients. Most commonly
reported symptoms of septicemia are fever,
dyspnea, diarrhea and vomiting (Alam et al.,
2012).
Most common sites of origin of
septicemia are the urinary tract (Rossignol et al.,
2016) and lungs. Novel and most effective
approaches are urgently required for treating
such infections. Bacteria can invade and
contaminate intravenous lines at the site of
puncture or wound and lead to septicemia. The
situation can be controlled by the use of new
skin disinfectants and by avoiding infusion
pauses with interruption of intravenous lines and
to replace the caps for the stopcocks with new
ones each time the caps are removed. These
measures are helpful in reducing the incidence
S

R. MEHBOOB ET AL.
88
of septicemia due to the Bacillus spp.
(Matsumoto et al., 2000).
The present study was done to evaluate
alterations in LFTs, RFTs and blood cells, major
causes, etiological factors and gender wise
distribution of septicemia in a tertiary care
hospital in Lahore, Pakistan.
MATERIAL AND METHODS
In this cross-sectional, observational and
Descriptive Study, 101 diagnosed patients of
septicemia with age more than 30 years were
included from the medical wards and Accident
and Emergency Department of Mayo Hospital
Lahore, while children, pregnant or lactating
women were excluded from the study.
In order to determine the etiology of the
disease at the time of presentation, these
patients have been carefully examined. Consent
was taken from the patients. All other ethical
issues were considered during the process of
data collection.
Table I: Normal ranges of biochemical and
hematological profiles
Sr.
No.
Parameters
Normal
Ranges
1.
Bilirubin
0.1-1.0mg/dl
2.
3.
AST
ALT
8-48 IU/L
7-55IU/L
4.
Alkaline phosphatase
45-115U/L
5.
Albumin
3.5-5.3mg/dl
6.
Total Protein
6.0-8.5g/dl
7.
Glucose
70-110mg/dl
8.
Urea
15-45mg/dl
9.
Creatinine
0.8-1.4mg/dl
10.
Na+
135-145meq/l
11.
K+
3.5-5.5meq/l
12.
White blood cells
4-10.510³/ul
13.
Platelets
150-45010³/ul
14.
Hemoglobin Male
13.5-17g/dl
15.
Hemoglobin Female
12-15g/dl
Data was recorded on a Performa
specially designed for this purpose. Patients
were divided into three age groups; 30-50 years,
51-70 years and 71-90 years, respectively.
Majority of the patients were between 51-70
years (39/101; 39.39%), whereas 37 patients
(37.37%) were between 30-50 years and 25
patients (25.25%) were in age range of 71- 90
years. There were 51 males and 50 females with
mean age of males 60.37±18.65 and for females
mean age was 55.02±17.206 (Table I). For each
patient liver function tests, renal function tests
and complete blood count was carried out.
Renal function tests performed in this study
were urea and creatinine (Table I) and Liver
function tests were bilirubin, alanine
aminotransferase (ALT), aspartate
aminotransferse (AST), alkaline phosphatase
(ALP), albumin and serum total protein (Table I)
while the electrolytes studied were Na+ and K+
(Table I). Blood glucose levels were also
measured (Table I). Hematological tests (CBC)
were white blood cells count, platelets and
hemoglobin (Table I).
RESULTS
51 patients were diabetic, 23 were
smokers and 27 had history of hypertension
(Figure 1). Bilirubin and K+ were normal
whereas urea and creatinine were high in
majority of patients in all three age groups.
Glucose was normal in 17.82% in 1st age group
(30-50) but was high in 24.78% in 2nd age group
(51-70) and 17.82% patients of 3rd age group
(71-90). Na+ was normal in 1stand 3rd age group
patients but was low in patients in 2nd age group.
The ALT was normal in most of the patients in
all three groups. Variation was not observed
according to age groups in these patients (Table
II).
Diabetic
50%
Smokers
23%
Hyperten
sive
27%
Figure 1: Risk Factors of Septicemia
observed in this study
The ALP, total protein and albumin were
almost same for both genders. ALT was raised
in 48.51%, AST in 50.50% and ALP in 99% of

ETIOLOGY OF SPETICEMIA IN PAKISTAN
89
patients. Variations in WBCs, platelets and
hemoglobin were same in both genders (Table
III).
UTI
BS
CI
WI
Others
0
5
10
15
20
25
30
35
Causes of septecemia
No. of patients
Figure 2: All causes of septicemia observed
in this study
Bilirubin, total protein and electrolytes
were normal whereas glucose was high in
55.45%. More males had raised blood glucose
levels (64.70%) compared to females (46%).
Urea was high in 71.29% and creatinine was
high in 52.48% of patients. WBC’s were high in
84.16% whereas platelets were low in 36.63%
and hemoglobin was low in 78.21% patients
(Table III-IV).
Causes of Septicemia
Around thirty different causes of
septicemia were observed during this study and
in few patients multiple causes of septicemia
were also seen. Most common causes were UTI
(32/101), bed sores (18/101), chest infection
(13/101), wound infection (8/101), aspiration
pneumonia (6/101), brain injury (5/101),diabetic
foot (4/101) ( Fig. 2).
Table II: Age wise variations in Biochemical and hematological profiles
Patients (%)
30-50 years
51-70 years
71-90 years
Parameters
L
N
H
L
N
H
L
N
H
Biliribin
0
30.69
5.940
0
32.67
5.94
0
18.811
5.940
AST
0
17.82
18.81
0
19.80
18.81
0
11.88
12.87
ALT
0
22.77
13.86
0
22.77
15.84
0
16.83
7.92
ALP
0
0.99
35.64
0
0
38.61
0
0
24.75
T. Protein
0.990
35.64
0
1.980
36.63
0
0
24.75
0
Albumin
12.87
23.76
0
17.82
20.79
0
13.86
10.89
0
Glucose
2.970
17.82
15.841
2.970
13.861
21.782
0.990
5.940
17.821
Urea
0
16.831
19.801
0
7.920
30.693
0
3.960
20.79
Creatinine
12.871
9.900
13.861
2.970
9.900
25.742
2.970
9.900
11.88
Na
12.871
21.782
1.980
18.811
16.831
2.970
9.900
14.851
0
K
3.960
31.683
0.990
5.94
32.67
0
1.980
21.78
0.990
WBC
0
7.920
28.71
0
5.940
32.67
0
1.980
22.77
Platelets
13.86
19.80
2.970
10.89
26.732
0.990
11.88
11.88
0.990
Hemoglobin (M)
12.87
2.970
0
14.85
2.970
0
14.85
1.980
0
Hemoglobin (F)
15.84
4.950
0
14.85
3.960
1.980
4.950
1.980
0.990
L (low), N (Normal), H (High), M (Males), F (Females)

R. MEHBOOB ET AL.
90
1) Septicemia due to UTI
The 16 patients out of 32 were males
and others females. Bilirubin, ALT, total protein
and electrolytes was normal in majority of
patients. Glucose was high in 56.87%. Urea was
high in 68.75% whereas creatinine was also
elevated in 59.37%. AST was high in 56.25%
and ALP in all the patients. Albumin was low in
56.25% patients. WBCs were high in 84.37%
whereas platelets were low in 50% and
hemoglobin was low in 78.12% (Table IV).
2) Septicemia due to Bed Sores
The 9 patients were males and 9 were females.
Bilirubin, electrolytes, ALT, AST and total protein
was normal. Blood glucose was high in 56.87%
whereas urea was high in 68.75%. Creatinine
was high in 44.44%. ALP was high in all bed
sores patients and albumin was low in 55.55%
patients. WBCs were high in 83.33% and
platelets were low in 44.44% whereas
hemoglobin was low in 83.33% patients (Table
IV).
Table III: Gender wise variations in all biochemical parameters
Males (%)
Females (%)
Parameter
L
N
H
L
N
H
Biliribin
0
86.27
13.72
0
78
22
AST
0
49.01
50.18
0
50
50
ALT
0
64.70
38.29
0
38
62
ALP
0
1.96
98.03
0
0
100
T. Protein
5.88
94.11
0
0
100
0
Albumin
41.17
58.82
0
48
52
0
Glucose
5.88
29.41
64.70
8
46
46
Urea
0
27.45
72.54
0
30
70
Creatinine
19.60
29.41
50.98
18
28
54
Na
45.09
49.01
5.88
38
58
4
K
9.80
88.23
1.96
14
84
2
WBC
0
17.64
82.32
0
14
86
Platelets
39.21
54.90
5.88
34
62
4
Hemoglobin
84.31
15.68
0
72
22
6
L (Low), N (Normal), H (High)
3) Septicemia due to Chest Infection
Chest infection as a cause of septicemia
was seen in 13 patients, 8 males and 5 females.
Bilirubin, ALT, total protein & electrolytes were
normal, while glucose was high in 69.23%, urea
was high in 61.53% and creatinine was high in
46.15%.
Albumin was low in 61.53 % and AST
was raised in 46.15% whereas ALP was high in
all. WBCs were high in 76.92% and platelets
were low in 30.76% whereas hemoglobin was
low in 76.92% (Table IV).
4) Septicemia due to Wound Infection
5 patients were males and 3 were females.
Bilirubin, total protein and K+ were normal in
most of the patients with wound infections, while
62.5% patients had low Na+, 50% had low
albumin and glucose was high in 62.5% (Table
IV).

ETIOLOGY OF SPETICEMIA IN PAKISTAN
91
Table IV: Variations in all biochemical and hematological parameters
Patients (%)
Bilirubin
UTI
UTI
UTI
UTI
87.5
87.5
87.5
87.5
Alanine aminotransferase (ALT)
UTI
BS
CI
WI
87.5
72.2
61.53
62.5
Aspartate aminotransferase (AST)
UTI
BS
CI
WI
56.2
55.5
53.8
75
Alkaline phosphatase (ALP)
UTI
BS
CI
WI
100
100
100
100
Albumin (ALB)
UTI
BS
CI
WI
56.25
55.55
61.53
50
Total Protein
UTI
BS
CI
WI
100
100
100
100
Glucose
UTI
BS
CI
WI
56.8
56.8
69.2
62.5
Urea
UTI
BS
CI
WI
68.7
68.7
61.5
87.5
Creatinine
UTI
BS
CI
WI
59.3
44.4
46.15
87.5
Electrolytes (Na/K)
UTI
BS
CI
WI
62.5
66.6
69.2
62.5
White blood cells (WBC’s)
UTI
BS
CI
WI
84.37
83.33
76.92
87.5
Platelets
UTI
BS
CI
WI
50
44.44
30.76
37.5
Hemoglobin
UTI
BS
CI
WI
78.12
83.33
76.92
75
UTI (Urinary tract infection), BS (Bed sores), CI (Chest infection), WI (Wound infection)
DISCUSSION
Septicemia has become a leading cause
of death in hospital settings (Dellinger 2016).
Among different diagnostic tests such as
procalcitonin (Sridharan and Chamberlain,
2013), interleukin 6, C-reactive protein (Fink-
Neuboeck et al., 2016) hematological tests, liver
function tests, renal function tests etc.,
hematological, liver and renal function tests are
widely used for diagnosing septicemia. These
tests are performed to assess deranged blood
picture and the function of liver and kidney
during diseased state. Liver dysfunction is
usually viewed as late feature of septicemia
(Recknagel et al., 2012). Hyper-bilirubinemia is
commonly seen during critical illness and often
results in adverse outcome (Vanwijngaerden et
al., 2011). According to a study, hyper-

R. MEHBOOB ET AL.
92
bilirubinemia and increased ALP are the
indicatives of septicemia (Brooks et al., 1991).
Extremely high levels of ALP and a normal
bilirubin was also seen (Maldonado et al., 1998).
In our study, ALP was high in all, whereas
bilirubin was normal in most of the patients
(82.18%).
Elevated peripheral white blood cell
count, elevated serum levels of ALP, bilirubin,
creatinine, potassium, urea and reduced serum
albumin levels were also observed in another
study (Young et al., 1990). Abnormality in
hematologic system takes place in almost every
patient of septicemia. Anemia, leukocytosis and
thrombocytopenia are the most common
abnormalities (Aird, 2003). In a study conducted
in Bangladesh, white blood cells count or TLC
did not show any positive result in diagnosing
septicemia but thrombocytopenia was present in
50% of cases (Mannan et al., 2010). In our
study, WBCs were elevated in 84.16% and
platelets were normal in 58.41% patients.
Increased WBCs count and decreased
hemoglobin (Hb) predicts infection (Gille-
Johnson et al., 2012). Hemoglobin was low in
our study, which is an indicative of anemia and
78.12% patients with UTI were anemic (Table
IV).
Urinary tract is found to be the most
likely sites of the origin of the septicemia
followed by lungs (Saint, Greene et al. 2016) . In
our study, different causes of septicemia were
seen but UTI came out to be the major cause of
septicemia followed by bed sores, chest
infection and wound infection (Fig. 2).
Risk factors that significantly and
independently increase the death rate in
septicemia are age, male sex, history of
diabetes, smoking (Godwin et al., 2016) and
disability in activities of daily living. Diabetes
increases the susceptibility to infection and
septicemia (Koh et al., 2012). Moreover,
diabetes is one of the most common co-
morbidity present in patients with sepsis (Esper
et al., 2009). Diabetes was seen in 50.49%
cases in our study and was the most common
risk factor. Smoking adversely affects the
immune system, respiratory tract, skin and soft
tissues and it is a risk factor for septicemia
(Huttunen et al., 2011). In addition, in our study,
males and females were equally affected by
septicemia (50.50% males, 49.0% females).
Except for ALT which was normal in majority of
males (64.70%) but elevated in females (62%),
all tests done in this study had almost same
results for both males and females (Table III).
Immunocompromised patients are at
greater risk for developing bloodstream
infections, such as septicemia (Papagheorghe
2012). Better early life conditions aids in better
development of adaptive immunity, which may
enhance immunity against bacterial infections
(Wong et al., 2012). A research done in USA
confirms that vitamin D and solar UVB plays an
important role in reducing the risk of septicemia
(Grant, 2009). In addition, improving nutritional
status is also helpful in reducing the risk of
septicemia (Jaar et al., 2000). Moreover, patient
should take care of personal hygiene. There
should be proper management of a surgical
wounds, cuts and pricks. Proper medical
treatment is also needed along with prophylactic
antibiotics and a regular medical checkup.
CONCLUSION
Septicemia is mainly a personal hygiene
related disease, so it can be greatly reduced by
taking proper hygienic measures. In this study
Mostly, there was no difference in biochemical &
hematological parameters gender wise but
where derangement was observed, it was in
male patients. Major risk factors of septicemia
were old age, low socioeconomic status,
hypertension and diabetes. It is highly
recommended to enhance awareness regarding
septicemia, its proper treatment with proper
antibiotics & good hydration as well as
importance of personal hygiene. In Pakistan,
there is a need to use improved diagnostic
biomarkers (e.g. PCT, genetic markers, C-
reactive protein etc) as being used in many
developed countries to achieve promising
accuracy.
REFERENCES
AIRD, W.C., 2003. The hematologic system as a
marker of organ dysfunction in
sepsis.Mayo Clin Proc., 78(7): 869-881.
ALAM, M.S., PILLAI, P.K., ET AL. 2012.
Antimicrobial therapy and outcome of
septicemia patients admitted to a
University Hospital in Delhi.
Arzneimittelforschung. 62(3): 117-122.
BROOKS, G.S., ZIMBLER, A.G. ET AL. 1991.
Patterns of liver test abnormalities in
patients with surgical sepsis. Am Surg.
57(10): 656-662.
DELLINGER, E.P., 2016. Prevention of Hospital-
Acquired Infections. Surg Infect
(Larchmt). (in press)

ETIOLOGY OF SPETICEMIA IN PAKISTAN
93
ESPER, A. M., MOSS, M., ET AL., 2009. The
effect of diabetes mellitus on organ
dysfunction with sepsis: an
epidemiological study. Crit Care, 13(1):
R18.
FINK-NEUBOECK, N., LINDENMANN, J., ET
AL. 2016. Clinical impact of interleukin 6
as a predictive biomarker in the early
diagnosis of postoperative systemic
inflammatory response syndrome after
major thoracic surgery: A prospective
clinical trial.Surgery. (in press)
GILLE-JOHNSON, P., HANSSON, K.E., ET AL.
2012. Clinical and laboratory variables
identifying bacterial infection and
bacteraemia in the emergency
department.Scand J Infect Dis., 44(10):
745-752.
GODWIN, C.A., LINDER, B.J., ET AL., 2016.
Effects of Smoking Status on Device
Survival Among Individuals Undergoing
Artificial Urinary Sphincter Placement.
Am. J Mens. Health.,(in press)
GRANT, W.B., 2009. Solar ultraviolet-B
irradiance and vitamin D may reduce the
risk of septicemia. Dermatoendocrinol.,
1(1): 37-42.
HUTTUNEN, R., HEIKKINEN, T., ET AL., 2011.
Smoking and the outcome of infection.J
Intern. Med., 269(3): 258-269.
JAAR, B.G., HERMANN, J.A., ET AL., 2000.
Septicemia in diabetic hemodialysis
patients: comparison of incidence, risk
factors, and mortality with nondiabetic
hemodialysis patients. Am J Kidney
Dis., 35(2): 282-292.
KOH, G.C., PEACOCK, S.J., ET AL., 2012. The
impact of diabetes on the pathogenesis
of sepsis. Eur. J. Clin. Microbiol. Infect.
Dis., 31(4): 379-388.
MALDONADO, O., DEMASI, R., ET AL. 1998.
Extremely high levels of alkaline
phosphatase in hospitalized patients.J
Clin. Gastroenterol, 27(4): 342-345.
MANNAN, M.A., SHAHIDULLAH, M., ET AL.,
2010. Utility of C-reactive protein and
hematological parameters in the
detection of neonatal sepsis.
Mymensingh Med J., 19(2): 259-263.
MATSUMOTO, S., SUENAGA, H. ET AL., 2000.
Management of suspected nosocomial
infection: an audit of 19 hospitalized
patients with septicemia caused by
Bacillus species. Jpn J Infect Dis.53(5):
196-202.
MELVAN, J.N., SIGGINS, R.W., ET AL., 2011.
Suppression of the stem cell antigen-1
response and granulocyte lineage
expansion by alcohol during
septicemia.Crit Care Med., 39(9): 2121-
2130.
PAPAGHEORGHE, R. 2012. Bloodstream
infections in immunocompromised
hosts. Roum. Arch. Microbiol. Immunol.,
71(2): 87-94.
RECKNAGEL, P., GONNERT, F.A., ET AL.,
2012. Liver dysfunction and
phosphatidylinositol-3-kinase signalling
in early sepsis: experimental studies in
rodent models of peritonitis. PLoS Med.,
9(11): e1001338.
ROSSIGNOL, L., VAUX, S., ET AL., 2016.
Incidence of urinary tract infections and
antibiotic resistance in the outpatient
setting: a cross-sectional study.
Infection (in press).
SAINT, S., GREENE, M.T. ET AL., 2016. A
Program to Prevent Catheter-
Associated Urinary Tract Infection in
Acute Care. N. Engl. J. Med., 374(22):
2111-2119.
SRIDHARAN, P. AND CHAMBERLAIN, R.,
2013. The efficacy of procalcitonin as a
biomarker in the management of sepsis:
slaying dragons or tilting at windmills?
Surg Infect (Larchmt., 14(6): 489-511.
TARIQ, M., JAFRI, W., ET AL., 2009. Medical
mortality in Pakistan: experience at a
tertiary care hospital. Postgrad. Med.
J.,.85(1007): 470-474.
VANWIJNGAERDEN, Y.M., WAUTERS, J., ET
AL., 2011. Critical illness evokes
elevated circulating bile acids related to
altered hepatic transporter and nuclear
receptor expression. Hepatology, 54(5):
1741-1752.
WONG, I.O., COWLING, B.J., ET AL., 2012.
Trends in mortality from septicaemia
and pneumonia with economic
development: an age-period-cohort
analysis.PLoS One, 7(6): e38988.
YOUNG, G.B., BOLTON, C.F., ET AL. 1990.
The encephalopathy associated with
septic illness. Clin. Invest. Med., 13(6):
297-304.