PCR project: Round 2

An initial look of the extended chart review

If you want to cut to the chase, the results presented for the abstract can be found here, along with their tables and figures. This page also details the methods for the length of stay (LOS) and duration of therapy (DOT) models.

Prep work

Missing data imputation

Similar to before, we don’t have much missing data, with only a few patients missing gestational age and birth weight

We’ll impute those now

Defining categories

First, we’ll collapse Race into larger categories, since we really have 3 common races recorded (including a large “other” group). Therefore, any race that shows up fewer than 10 times will be lumped together with “Other”. We’ll also recode BCx to where CONS is considered “other” like the other contaminants

Next we make a new wt_for_GA category that compares the patients gestational age & weight to the national Z-scores. Data comes from Talge et al., 2014, and uses less than the 10th percentile for SGA and greater than the 90th percentile for LGA. Because so few patients are LGA, this category is combined with AGA. We’ll also make categories for LBW (less than 2500 gram, regardless of GA) and prematurity (GA < 37).

Descriptive Statitics

This is the basic Table 1 for our results, showing descriptive statistics of included patients stratified by era

Table 1 Era: Post-PCR (N = 66) Era: Pre-PCR (N = 52)
los      
   Mean (95% CI) 47.63 (42.57 - 52.69) 56.00 (50.93 - 61.07)
   Median (IQR) 46.9 (32.6, 55.8) 56.1 (46.1, 68.3)
   Range 12.8 to 122.4 14.2 to 110.8
DOT      
   Mean (95% CI) 23.69 (18.63 - 28.74) 56.50 (43.85 - 69.16)
   Median (IQR) 26.6 (0.0, 43.3) 48.0 (15.2, 93.2)
   Range 0 to 59.7 0 to 158
Diagnosis      
   FUO 26 (39.4%) 19 (36.5%)
   Viral 40 (60.6%) 33 (63.5%)
TempInst      
   Both 0 (0.0%) 1 (1.9%)
   ERROR 0 (0.0%) 1 (1.9%)
   Fever 54 (81.8%) 40 (76.9%)
   Hypothermia 11 (16.7%) 7 (13.5%)
   None 1 (1.5%) 3 (5.8%)
Sex      
   Female 31 (47.0%) 19 (36.5%)
   Male 35 (53.0%) 33 (63.5%)
Age      
   Mean (95% CI) 28.44 (23.00 - 33.87) 31.08 (25.18 - 36.98)
   Median (IQR) 22.0 (7.2, 44.8) 29.0 (11.0, 50.0)
   Range 2 to 87 2 to 76
GA      
   Mean (95% CI) 38.33 (37.90 - 38.75) 38.30 (37.90 - 38.71)
   Median (IQR) 39.0 (37.6, 39.1) 39.0 (37.2, 39.2)
   Range 33 to 41 34.5 to 40.6
birth_weight      
   Mean (95% CI) 3,086.05 (2,963.15 - 3,208.94) 3,133.96 (3,009.84 - 3,258.08)
   Median (IQR) 3,153.0 (2,812.5, 3,417.5) 3,136.0 (2,855.0, 3,462.8)
   Range 1760 to 4196 2070 to 4270
Race      
   Black 8 (12.1%) 12 (23.1%)
   White 47 (71.2%) 26 (50.0%)
   Other 11 (16.7%) 14 (26.9%)
wt_for_GA      
   AGA 57 (86.4%) 42 (80.8%)
   SGA 9 (13.6%) 10 (19.2%)
LBW      
   LBW 8 (12.1%) 5 (9.6%)
prematurity      
   Premature 8 (12.1%) 8 (15.4%)
   Term 58 (87.9%) 44 (84.6%)
Resp_PCR      
   Pre-PCR 0 (0.0%) 52 (100.0%)
   negative 19 (28.8%) 0 (0.0%)
   Not Done 18 (27.3%) 0 (0.0%)
   Virus 29 (43.9%) 0 (0.0%)
CSF_PCR      
   negative 22 (33.3%) 0 (0.0%)
   Not Done 32 (48.5%) 0 (0.0%)
   Pre_PCR 0 (0.0%) 52 (100.0%)
   Virus 12 (18.2%) 0 (0.0%)

Table 2 shows results for the PCR era only, comparing the simplified diagnosis with results of the PCRs

Table 2 Diagnosis: FUO (N = 26) Diagnosis: Viral (N = 40)
Resp_PCR      
   Pre-PCR 0 (0.0%) 0 (0.0%)
   negative 13 (50.0%) 6 (15.0%)
   Not Done 12 (46.2%) 6 (15.0%)
   Virus 1 (3.8%) 28 (70.0%)
CSF_PCR      
   negative 13 (50.0%) 9 (22.5%)
   Not Done 13 (50.0%) 19 (47.5%)
   Virus 0 (0.0%) 12 (30.0%)

Length of Stay

Bivariate analysis: t-test

Welch Two Sample t-test: los by Era (continued below)
Test statistic df P value Alternative hypothesis
-2.29 114.3 0.02384 * two.sided
mean in group Post-PCR mean in group Pre-PCR
47.63 56

DOT

Bivariate analysis: Mann-Whitney U Test (nonparametric d/t non-normality)

Wilcoxon rank sum test with continuity correction: DOT by Era (continued below)
Test statistic P value Alternative hypothesis
1025 0.0001539 * * * two.sided
difference in location
-28

Excluded patients

Here’s a summary of how many patients were included/excluded:

Patient status n
Included 118
Those admitted with a known infection/focal infection or later diagnosed with bacterial infection 38
No sepsis evaluation done or not concerned for sepsis on admission 13
Age out of range 9
Multiple reasons 8
Those with underlying medical condition 4
Duplicate patient 3
Those requiring admission or transfer to PICU 3
Inpatient transfer from another unit or OSH or transfer to another hospital 1

Patients with multiple reasons for exclusion are coded as multiple reasons in the table above. If we look at only the 79 excluded patients, here are their non-mutually exclusive reason(s) for exclusion

Reasons for exclusion
# excluded % of excluded % of total
(1) Those admitted with a known infection/focal infection or later diagnosed with bacterial infection 43 54.43% 21.83%
(2) Those with underlying medical condition 10 12.66% 5.08%
(3) Those requiring admission or transfer to PICU 3 3.80% 1.52%
(4) Inpatient transfer from another unit or OSH or transfer to another hospital 4 5.06% 2.03%
(6) No sepsis evaluation done or not concerned for sepsis on admission 15 18.99% 7.61%
(7) Age out of range 10 12.66% 5.08%
(8) Duplicate patient 4 5.06% 2.03%

Unfortunately, we don’t have demographics on excluded patients (i.e. age, sex, PCR-era) so we can’t compare them to included patients. Shouldn’t be a problem for the abstract, but should probably be done if this becomes a paper. For what it’s worth, we already have 23 records for excluded patients in RedCap.

Antibiotics

Here’s a quick look at the antibiotic usage over the two eras

Antibiotic use by Era
Only antibiotics given during both eras are presented
# patients received Mean Median
Post-PCR Pre-PCR Post-PCR Pre-PCR Post-PCR Pre-PCR
acyclovir 19 13 5.96 (2.81 - 9.12) 8.62 (4.29 - 12.94) 3.0 6.0
ampicillin 39 35 35.15 (30.50 - 39.80) 40.72 (35.36 - 46.08) 39.0 45.0
cefoTAXime 2 26 29.00 (-21.96 - 79.96) 45.45 (39.41 - 51.48) 29.0 47.0
cefTAZidime 24 4 34.38 (28.02 - 40.74) 41.25 (34.59 - 47.91) 37.5 42.5
cefTRIaxone 15 3 31.08 (24.35 - 37.81) 40.67 (11.77 - 69.57) 31.3 39.0
gentamicin 9 9 16.10 (2.30 - 29.91) 43.78 (32.72 - 54.84) 3.0 46.0
none 21 11
vancomycin 4 4 27.25 (4.33 - 50.17) 41.75 (14.15 - 69.35) 25.5 50.5

Because it looks like we were using different cephalosporins in both eras, here are the results pooling all the cephalosporins together1

Results for Cephalosporins in the aggregate
# patients received Mean* Median*
Post-PCR 40 33.73 (29.05 - 38.41) 35.05
Pre-PCR 33 44.50 (39.21 - 49.80) 46.00

* Calculated from the sum of all cephalosporins for each patient

Modeling LOS & DOT

We’ll likely have to take two separate approaches for modeling these, since they follow different distributions. Specifically, DOT is zero inflated while LOS is not

LOS model

LOS is simple, just use a Poisson GLM

term IRR LL UL p.value
(Intercept) 49.82 41.08 60.42 < 0.001 *
EraPre_PCR 1.162 1.02 1.33 0.027 *
wt_for_GASGA 1.063 0.88 1.29 0.54
Simple_DxViral 0.9613 0.82 1.13 0.63
Age 0.9981 0.99 1 0.28
BCxContaminant 1.13 0.92 1.39 0.25
SexMale 1.031 0.9 1.18 0.67

The table above is transformed to show incidence rate ratio (IRR), which can be thought of as the relative risk2. Thus the coefficient can be thought of as follows:

The LOS was 1.16 times longer in the Pre-PCR era, compared to the Post-PCR era, when adjusting for the above variables

This can be demonstrated by looking at the conditional means in the two eras

Conditional means for LOS
Era Conditional Mean conf.low conf.high
Post-PCR 49.66 46.88 52.61
Pre_PCR 57.68 54.71 60.81

The results of the regression graphically:

And conditional mean LOS by each covariate:

DOT model

For DOT we have a more complicated picture, since we have lots of zeros3 in the response variable. We’ll use a zero-inflated model, which is kind of a 2-in-1 solution that addresses two questions:

  1. Who got any antibiotics? Called the zero-inflated model, which is a logistic regression
  2. Among those who did get antibiotics, how much did they get? Called the conditional model, which works just like to LOS model but is only applied to patients with non-zero DOT’s

Here’s our model:

##  Family: genpois  ( log )
## Formula:          DOT ~ Era + wt_for_GA + Simple_Dx + BCx + Sex
## Zero inflation:       ~Era + wt_for_GA + Simple_Dx + Age
## Data: subj_rounded
## 
##      AIC      BIC   logLik deviance df.resid 
##    954.9    988.2   -465.5    930.9      106 
## 
## 
## Overdispersion parameter for genpois family (): 19.4 
## 
## Conditional model:
##                Estimate Std. Error z value Pr(>|z|)    
## (Intercept)     3.63194    0.14455  25.125  < 2e-16 ***
## EraPre_PCR      0.66856    0.11776   5.677 1.37e-08 ***
## wt_for_GASGA   -0.06666    0.15094  -0.442  0.65875    
## Simple_DxViral -0.25768    0.12196  -2.113  0.03461 *  
## BCxContaminant  0.44643    0.16345   2.731  0.00631 ** 
## SexMale         0.13253    0.11807   1.122  0.26165    
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Zero-inflation model:
##                Estimate Std. Error z value Pr(>|z|)   
## (Intercept)    -1.06751    0.44348  -2.407  0.01608 * 
## EraPre_PCR     -0.49930    0.44432  -1.124  0.26112   
## wt_for_GASGA   -0.54999    0.63718  -0.863  0.38804   
## Simple_DxViral -0.83465    0.46436  -1.797  0.07227 . 
## Age             0.02879    0.01012   2.846  0.00443 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

The same results, shown as a figure:

Looking at the results of the model above4, we see that Age is significant for the logistic regression. The odds ratio of not receiving any antibiotics was 0.43 for those who were ultimately diagnosed with a viral infection, but this wasn’t significant. Of note, the OR for those in the Pre-PCR era (OR = 0.61) is not significant.

Moving up to the conditional regression, we can see that the DOT was 1.95 times longer in the Pre-PCR era, compared to the Post-PCR era. We also can see that patients with contaminants on their blood culture had a longer duration of antibiotics, which makes sense.

The conditional means for each era are presented below:

Fixed effects for DOT
Era Conditional Mean conf.low conf.high
Post-PCR 41.68 32.58 53.32
Pre_PCR 81.33 65.58 100.9

For the abstract

Methods

We performed a retrospective chart review of infants younger than 90 days old who were admitted to the pediatric ward for concerns of fever or sepsis from 1/1/2015 to 9/30/2019. Subjects with documented bacterial infections were excluded. Our primary outcomes were differences in DOT and LOS between patients admitted before and after PCRs became available (Pre-PCR era and PCR era).

Results

118 subjects were included in our analysis, with 52 (44.1%) coming from the Pre-PCR group. Descriptive statistics, stratified by era, are available in Table 1. The unadjusted mean LOS and DOT decreased by 8.4 (P = .0035) and 32.8 (P < .0016) hours, respectively.

Multivariate regression demonstrated that LOS was 1.16 times longer in the Pre-PCR era (95% CI: 1.1 - 1.22; P < .001). Similarly, patients in the Pre-PCR era had DOT that was 1.95 times longer (95% CI: 1.55 - 2.46; P < .001) when adjusting for covariates.

Tables / Figures

Abstract Table 1

Abstract Table 1 Era: Post-PCR (N = 66) Era: Pre-PCR (N = 52)
Age on admission (days)      
   Mean (95% CI) 28.44 (23.00 - 33.87) 31.08 (25.18 - 36.98)
   Median (IQR) 22.0 (7.2, 44.8) 29.0 (11.0, 50.0)
   Range 2 to 87 2 to 76
Sex      
   Female 31 (47.0%) 19 (36.5%)
   Male 35 (53.0%) 33 (63.5%)
Race      
   Black 8 (12.1%) 12 (23.1%)
   White 47 (71.2%) 26 (50.0%)
   Other 11 (16.7%) 14 (26.9%)
Gestational age (weeks)      
   Mean (95% CI) 38.33 (37.90 - 38.75) 38.30 (37.90 - 38.71)
   Median (IQR) 39.0 (37.6, 39.1) 39.0 (37.2, 39.2)
   Range 33 to 41 34.5 to 40.6
Birth weight (grams)      
   Mean (95% CI) 3,086.05 (2,963.15 - 3,208.94) 3,133.96 (3,009.84 - 3,258.08)
   Median (IQR) 3,153.0 (2,812.5, 3,417.5) 3,136.0 (2,855.0, 3,462.8)
   Range 1760 to 4196 2070 to 4270
Birth weight for gestational age      
   AGA 57 (86.4%) 42 (80.8%)
   SGA 9 (13.6%) 10 (19.2%)

Abstract Table 2

Abstract Table 2 Era: Post-PCR (N = 66) Era: Pre-PCR (N = 52)
Length of stay (hours)      
   Mean (95% CI) 47.64 (42.57 - 52.70) 56.10 (51.01 - 61.18)
   Median (IQR) 47.0 (32.2, 56.0) 56.5 (46.2, 68.5)
   Range 13 to 122 14 to 111
Duration of therapy (hours)      
   Mean (95% CI) 23.70 (18.64 - 28.75) 56.50 (43.84 - 69.16)
   Median (IQR) 26.5 (0.0, 43.5) 48.0 (15.2, 93.2)
   Range 0 to 60 0 to 158
Discharge diagnosis      
   FUO 26 (39.4%) 19 (36.5%)
   Viral 40 (60.6%) 33 (63.5%)
Respiratory PCR result      
   Pre-PCR 0 (0.0%) 52 (100.0%)
   Negative 19 (28.8%) 0 (0.0%)
   Not Done 18 (27.3%) 0 (0.0%)
   Virus 29 (43.9%) 0 (0.0%)
Meningoencephalitis PCR result      
   Negative 22 (33.3%) 0 (0.0%)
   Not Done 32 (48.5%) 0 (0.0%)
   Pre-PCR 0 (0.0%) 52 (100.0%)
   Virus 12 (18.2%) 0 (0.0%)
Blood culture      
   No growth/not done 63 (95.5%) 44 (84.6%)
   Contaminant 3 (4.5%) 8 (15.4%)

Abstract Figure 1

Figure 1: Multivariate adjusted estimates for the average length of stay [A] and duration of antibiotic therapy [B], stratified by discharge diagnosis (vertical panels) and PCR era (y-axis). Estimates (with 95% CI’s) are adjusted for Age, BCx, Era, Sex, Simple_Dx, wt_for_GA

Abstract Figure 2

Figure 2: Results of the positive PCR panels by pathogen. Note that some patients appear in the figure more than once (e.g. if a patient had a respiratory PCR positive for Rhinovirus/enterovirus and a meningoencephalitis PCR positive for Enterovirus). Patients with negative results for the respiratory (n=19) or meningoencephalitis (n=22) panels are not shown.

End

For the poster

Fig 1:

Table 1

Table 1 Era: Post-PCR (N = 66) Era: Pre-PCR (N = 52)
Age on admission (days)      
   Mean (95% CI) 28.44 (23.00 - 33.87) 31.08 (25.18 - 36.98)
   Median (IQR) 22.0 (7.2, 44.8) 29.0 (11.0, 50.0)
   Range 2 to 87 2 to 76
Sex      
   Female 31 (47.0%) 19 (36.5%)
   Male 35 (53.0%) 33 (63.5%)
Race      
   Black 8 (12.1%) 12 (23.1%)
   White 47 (71.2%) 26 (50.0%)
   Other 11 (16.7%) 14 (26.9%)
Gestational age (weeks)      
   Mean (95% CI) 38.33 (37.90 - 38.75) 38.30 (37.90 - 38.71)
   Median (IQR) 39.0 (37.6, 39.1) 39.0 (37.2, 39.2)
   Range 33 to 41 34.5 to 40.6
Birth weight (grams)      
   Mean (95% CI) 3,086.05 (2,963.15 - 3,208.94) 3,133.96 (3,009.84 - 3,258.08)
   Median (IQR) 3,153.0 (2,812.5, 3,417.5) 3,136.0 (2,855.0, 3,462.8)
   Range 1760 to 4196 2070 to 4270
Birth weight for gestational age      
   AGA 57 (86.4%) 42 (80.8%)
   SGA 9 (13.6%) 10 (19.2%)

Table 2

Table 2: Adjusted LOS & DOT
Zero-inflated DOT not shown
LOS DOT
IRR CI p IRR CI p
Era: Pre-PCR 1.16 [ 1.10, 1.22] < .001 1.95 [ 1.55, 2.46] < .001
Birth weight: SGA 1.06 [ 0.99, 1.14] 0.078 0.94 [ 0.70, 1.26] 0.659
Dx: Viral infection 0.96 [ 0.91, 1.02] 0.157 0.77 [ 0.61, 0.98] 0.035
Age (per week) 0.99 [ 0.98, 1.00] 0.003
BCx: Contaminant 1.13 [ 1.04, 1.23] 0.006 1.56 [ 1.13, 2.15] 0.006
Sex: Male 1.03 [ 0.98, 1.09] 0.259 1.14 [ 0.91, 1.44] 0.262

Fig 2

p median n
Post-PCR Pre-PCR Post-PCR Pre-PCR
acyclovir 0.463 3 [2 - 7] 6 [2 - 16] 19 13
ampicillin 0.077 39 [28 - 47] 45 [35 - 50] 39 35
cephalosporin 0.003 35 [24 - 45] 46 [39 - 56] 40 33
gentamicin 0.019 3 [2 - 38] 46 [45 - 50] 9 9
none NaN 0 [0 - 0] 0 [0 - 0] 21 11
vancomycin 0.561 26 [15 - 38] 50 [36 - 57] 4 4


  1. On the off chance that a patient was given two cephalosporins at the same time (e.g. got Rocephin from 00:00 to 02:00 and given ceftazidime from 01:00 to 06:00), this is the sum of the total duration of each (2 + 5 in this example), not the earliest admin to the last admin

  2. The actual interpretation is a bit more complicated, since we are technically modeling each hour of antibiotics as an event. Poisson distributions predict the number of events (e.g. number of lightning strikes) over a period of time. So it gets messy, but this is the best I can do for the time being

  3. See histogram at the start of the section

  4. At least for the run of the model at the time of writing. If the numbers no longer match up, it likely means the model has changed

  5. Via Wilcoxon rank sum test with continuity correction

  6. Via Wilcoxon rank sum test with continuity correction

Hunter Ratliff, MD, MPH
Hunter Ratliff, MD, MPH
Infectious Diseases Fellow

My research interests include epidemiology, social determinants of health, and reproducible research.

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