Abstract
Objective
This study assessed antiviral medication use for treatment of influenza-like illness (ILI) in Veterans with spinal cord injury or disorder (SCI/D) and examined whether antiviral prescribing improved over time.
Design
Retrospective cohort study of Department of Veterans Affairs (VA) facilities.
Participants
Veterans with SCI/D and matched non-SCI/D controls (matched by facility and date of visit/admission) who were diagnosed by a clinician with ILI during the period 1 October 2007 to 31 May 2010.
Main outcome measures
Antiviral receipt and appropriateness were examined. Appropriate antiviral prescribing was defined as patients who received an antiviral medication within 2 days of collection of a sample for diagnostic testing or within 2 days of symptom onset.
Results
We identified 101 influenza visits/admissions for veterans with SCI/D and 123 for controls. Antiviral prescribing for Veterans with SCI/D increased from 37.1% in 2007/2008 to 67.6% in 2009/2010 (P = 0.01) and appropriate antiviral prescribing increased from 20.0 to 41.2% (P = 0.05). Predictors of antiviral prescribing included being treated in the 2009/2010 influenza season (vs. 2007/2008) and having a cough. Fever, aches/myalgia, or a positive influenza test was associated with appropriate antiviral treatment. SCI/D was an independent predictor of receiving antiviral treatment (adjusted odds ratio = 1.16, 95% confidence interval 1.04–1.29), but having SCI/D was not associated with receiving appropriate treatment.
Conclusions
Influenza antiviral prescribing increased over time and in a larger proportion in veterans with SCI/D (vs. controls). This suggests that providers treating patients with SCI/D recognize treatment guidelines and their importance in a high-risk population. Continued efforts are needed to improve appropriate influenza antiviral prescribing.
Keywords: Influenza, Antivirals, Spinal cord injury, Appropriate prescribing
Introduction
The Centers for Disease Control and Prevention (CDC) have identified several high-risk groups for influenza and its complications; this includes persons with spinal cord injuries and disorders (SCI/D).1 Persons with SCI/D are at increased risk of respiratory illness which is associated with increased morbidity and mortality.2,3 Data from the Department of Veterans Affairs (VA) have shown that the annual rate of pneumonia and influenza in veterans with SCI/D is 30–35 annual outpatient visits per 1000 persons compared to the overall US population rate of 5.2–12.7 visits per 1000 persons.4–6 Persons with SCI are 37 times more likely to die from pneumonia and influenza than comparable individuals from the general population.7
The most effective method to prevent infection with influenza and its complications is annual influenza vaccination.8,9 The CDC recommends two antiviral medications, zanamivir and oseltamivir, as an adjunct to influenza vaccination due to their effectiveness for treatment of influenza and as a chemoprophylaxis after an exposure to influenza virus.10 In addition, antiviral treatment was recommended for all children and adults hospitalized with suspected or confirmed influenza during the 2009 influenza A (H1N1) pandemic.11
The purpose of this study was to examine the use of antiviral medications to treat influenza infection or influenza-like illness (ILI) in veterans with SCI/D and assess whether antiviral prescribing has improved over a timeframe.
Methods
Study design and setting
A retrospective medical record review was conducted on the study sample of all visits and admissions associated with an influenza diagnosis and/or antiviral prescription that occurred at any of the 152 medical centers and their associated ambulatory or community-based outpatient clinics between 1 October 2007 and 31 May 2010. The study was approved by the local institutional review board. Two groups were identified: veterans with SCI/D and a comparison group of veterans who did not have SCI/D. The comparison group was included to determine whether antiviral prescribing practices differed for those in the SCI/D population compared to the general veteran population.
Data collection and data sources
The initial data for this cohort was obtained from the VA Medical SAS datasets. These are administrative databases including demographic and utilization data for all VA facilities and are updated nightly with patient medical record information from the local VA facility.12,13 The National Patient Care Database (NPCD) was used to identify all visits and admissions with a diagnosis of influenza using ICD9 codes 487 and 488 (codes 488.0 and 488.1 became effective from October 2009, the latter indicating “influenza due to identified H1N1 virus”) that occurred during the study timeframe.
The VHA Decision Support System was used to identify all outpatient and inpatient prescriptions for oseltamivir and zanamivir for each patient. Each prescription was associated with an outpatient visit (within 3 days of visit) or hospitalization. Once all visits and admissions with an influenza diagnosis and/or with an antiviral prescription were identified, a medical chart review was conducted to further define a clinical diagnosis of influenza and appropriateness of treatment. The medical chart reviews were conducted by a qualified data abstractor who used a standardized data abstraction form to conduct the chart reviews. After identifying the sample with visits for influenza or antiviral prescriptions, a clinical diagnosis of influenza was defined as a patient with physician documentation in the medical record of influenza/ILI or positive rapid influenza cultures.
Study sample
Over 15 000 unique patients with SCI/D utilized VA facilities for any reason during the study time period and were eligible for inclusion. The sample was drawn based on having an influenza diagnosis and/or antiviral prescription during the study time period. The comparison group was a 1:1 matched sample of Veterans treated at VA facilities during the same timeframe who did not have SCI/D but also had a diagnosis of influenza and/or an antiviral prescription. The comparison group was matched by facility and date of visit/admission. For those who could not be matched by exact date, the timeframe was extended until a suitable match was achieved (maximum of 69 days from the encounter).
Measures
Demographics (age, ethnicity, sex), and comorbid diagnoses were extracted from the NPCD. Data collected from the medical chart review included a constellation of symptoms: the presence of and duration of fever (defined as temperature >38.0°C), headache, sore throat, cough, myalgia, physical examination findings (i.e. signs of influenza), diagnostic testing, treatments during the encounter, vaccinations, and other complications. SCI/D characteristics were also collected including level of injury (paraplegia or tetraplegia), duration of injury, and ASIA impairment score which measures completeness of injury (A = complete, no motor or sensory function in the lowest sacral segment (S4–S5); B = incomplete, sensory function below neurologic level and in S4–S5, no motor function below neurologic level; C = incomplete, motor function is preserved below neurologic level and more than half of the key muscle groups below neurologic level have a muscle grade <3; D = incomplete, motor function is preserved below neurologic level and at least half of the key muscle groups below neurologic level have a muscle grade >3; E = normal).14
Appropriate antiviral prescribing was defined as patients who received an antiviral medication within 2 days of collection of a sample for diagnostic testing or within 2 days of symptom onset including: fever (subjective and objective) and at least two additional symptoms including headache, sore throat, cough, or myalgia.15
Statistical analyses
The proportion of patients who received appropriate antiviral medications was calculated as the number of patients with appropriate antiviral treatment divided by the number of patients with a clinically or laboratory confirmed diagnosis of influenza. Antiviral treatment was described by SCI/D and non-SCI/D groups, demographics, SCI/D characteristics (age group, ethnicity, level of injury, traumatic vs. non-traumatic), and by the time periods. Matched analyses were conducted using McNemar's test. We compared the antiviral prescribing and appropriate prescribing by annual influenza season time periods (1 October 2007 to 30 September 2008, 1 October 2008 to 30 September 2009, and 1 October 2009 to 31 May 2010) using an overall test for trend. The last time period is shorter than the two previous time periods due to the availability of data at the time of analysis. Other factors associated with prescribing including time period, were included in GEE logistic regression models, accounting for clustering by facility for unmatched analyses. Some patients had more than one influenza encounter during the study timeframe; therefore, all analyses were conducted at the visit/admission level. For matched analyses, conditional logistic regression was used. All statistical analyses were considered statistically significant at the 0.05 level and performed using SAS version 9.2 (SAS Institute, Cary, NC, USA) and STATA SE version 11.0 (StataCorp LP, College Station, TX, USA).
Results
There were 176 visits/admissions for veterans with SCI/D identified with either a diagnosis of influenza or an antiviral prescribed during the study timeframe. A similar number of veterans without SCI/D were identified and matched to the SCI/D cohort. After excluding those that were admitted outside the study time period (n = 3), that had multiple sclerosis (n = 21), or had no indication of influenza or ILI but had been administered an influenza vaccine (n = 51), there were a total of 101 visits/admissions for 97 veterans with SCI/D with either an influenza diagnosis or suspected influenza. Similar exclusions were conducted with the comparison sample, resulting in 123 visits/admissions and 123 unique veterans without SCI/D. As a result, if part of a matched pair was excluded, the entire pair was removed for conditional logistic regression, resulting in 82 matched pairs. All influenza visits/admissions included in the study occurred between October and April, except during the H1N1 pandemic where cases continued to occur between May and September 2009.
Table 1 describes the demographics and medical characteristics of the study sample at the visit/admission level. Veterans with SCI/D were primarily male and white, with a mean age of 54.7 years (median = 56.0). The majority had tetraplegia (61.4%) and of those with ASIA Impairment Scale (AIS) data, over one-third had a complete injury (AIS level A) (39.5%). However, ∼25% of those with SCI were missing data on ASIA classification. Most encounters were outpatient visits and the majority of patients had been immunized against seasonal influenza. The SCI/D and control samples were similar across most of the patient and medical characteristics examined, with a few key exceptions. A statistically significant higher proportion of veterans with SCI/D were immunized against the H1N1 virus, had received the seasonal influenza vaccine, were diagnosed with pneumonia, and were admitted to the intensive care unit (ICU) compared to the control sample (Table 1).
Table 1 .
Study sample characteristics
| Demographic and medical characteristics | SCI | Non-SCI | Total | McNemar's test |
|---|---|---|---|---|
| Frequency (%) (N = 101) | Frequency (%) (N = 123) | Frequency (%) (N = 224) | P-value | |
| Age (years) | ||||
| < 50 | 31 (30.7) | 41 (33.3) | 72 (32.1) | Reference |
| 50–64 | 48 (47.5) | 43 (35.0) | 91 (40.6) | 1.00 |
| 65 + | 22 (21.8) | 39 (31.7) | 61 (27.3) | 0.23 |
| Mean, median (SD) | 54.7, 56.0 (15.1) | 56.7, 57.5 (15.7) | 55.8, 57.0 (15.4) | 0.35 |
| Race | ||||
| White | 73 (72.3) | 82 (66.7) | 155 (69.2) | Reference |
| Black | 20 (19.8) | 26 (21.1) | 46 (20.5) | 0.79 |
| Other | 8 (7.9) | 15 (12.2) | 23 (10.3) | 0.77 |
| Sex | ||||
| Male | 93 (92.1) | 109 (88.6) | 202 (90.2) | Reference |
| Female | 8 (7.9) | 14 (11.4) | 22 (9.8) | 0.79 |
| Smoking status | ||||
| Never smoked | 33 (32.7) | 45 (36.6) | 78 (34.8) | Reference |
| Past smoker | 36 (35.6) | 40 (32.5) | 76 (33.9) | 1.00 |
| Current smoker | 32 (31.7) | 38 (30.9) | 70 (31.3) | 0.27 |
| Level | ||||
| Paraplegia | 39 (38.6) | |||
| Tetraplegia | 62 (61.4) | |||
| ASIA impairment level | ||||
| A | 30 (29.7) | |||
| B | 12 (11.9) | |||
| C | 7 (6.9) | |||
| D | 27 (26.7) | |||
| Missing | 25 (24.8) | |||
| Duration of injury | ||||
| < 10 years | 26 (25.7) | |||
| 10–20 years | 19 (18.8) | |||
| > 20 years | 30 (29.7) | |||
| Missing | 26 (25.8) | |||
| Received seasonal influenza immunization | 70 (70.0) | 69 (59.5) | 139 (62.1) | <0.01 |
| Received H1N1 immunization | 41 (44.1) | 30 (27. 8) | 71 (31.7) | 0.02 |
| Inpatient encounter | 26 (25.7) | 21 (17.1) | 47 (21.0) | 0.11 |
| Time period | ||||
| 2007/2008* | 35 (34.7) | 46 (37.4) | 81 (36.2) | Reference |
| 2008/2009* | 32 (31.7) | 36 (29.3) | 68 (30.4) | 0.64 |
| 2009/2010† | 34 (33.6) | 41 (33.3) | 75 (33.4) | 0.79 |
| Other documented respiratory diagnoses | ||||
| Upper respiratory infection | 10 (9.9) | 14 (11.4) | 24 (10.7) | 0.48 |
| Bronchitis | 2 (2.0) | 1 (0.8) | 3 (1.3) | 1.00 |
| Pneumonia | 18 (17.8) | 8 (6.5) | 26 (11.6) | 0.01 |
| Reported symptoms | ||||
| Fever | 61 (60.4) | 86 (69.9) | 147 (65.6) | 0.08 |
| Headache | 23 (22.8) | 28 (22.8) | 51 (22.8) | 0.35 |
| Sore throat | 29 (28.7) | 32 (26.0) | 61 (27.2) | 0.73 |
| Cough | 65 (64.4) | 92 (74.8) | 157 (70.1) | 0.19 |
| Aches/myalgia | 47 (46.5) | 67 (54.5) | 114 (50.9) | 0.32 |
| Confirmed flu case | 64 (63.4) | 90 (73.2) | 154 (68.8) | 0.30 |
| Abnormal chest X-ray | 21 (20.8) | 24 (19.5) | 45 (20.1) | 0.50 |
| Positive influenza culture | 12 (36.4) | 20 (45.5) | 32 (41.6) | 0.33 |
| Severity measures | ||||
| Supplemental oxygen | 16 (15.8) | 7 (5.7) | 23 (10.3) | 0.15 |
| Admitted to ICU | 12 (11.9) | 7(5.7) | 19 (8.5) | 0.01 |
| Ventilator support | 5 (5.0) | 3 (2.4) | 8 (3.6) | 1.00 |
| Sepsis | 6 (5.9) | 4 (3.3) | 10 (4.5) | 1.00 |
*Time period is 1 October to 30 September.
†Time period is 1 October to 31 May.
Overall half (49.5%) of SCI/D patients in our sample received an antiviral during the study time period. Fig. 1 describes the percentage of influenza/ILI patient encounters with an antiviral prescribed or the percentage of prescribing that was appropriate. Antiviral prescribing for veterans with SCI/D increased from 37.1% in 2007/2008 to 67.6% in 2009/2010 (trend test P = 0.01) (Fig. 1). Appropriate antiviral prescribing increased from 20.0 to 41.2% (trend test P = 0.05). In addition, of the 50 patients with SCI/D who received an antiviral, the appropriateness of prescribing increased from 53.9 to 60.9%. Oseltamivir was prescribed in most instances (95.9%). Our matched comparison group had an even greater increase in antiviral prescribing between (17.4 and 58.5%, trend test P ≤ 0.0001) and in the appropriateness of treatment (8.7 to 41.5%, trend test P = 0.0005). Reasons for inappropriate influenza antiviral prescribing included not having a fever and/or at least two of the symptoms (headache, sore throat, cough, or myalgia) (30% of all antiviral prescriptions) or having had influenza symptoms for more than 2 days (12% of all antiviral prescriptions).
Figure 1 .
Antiviral prescribing and appropriateness of prescribing in SCI/D and control group over time.
Bivariate analyses of veterans with SCI/D, showed that patient and clinical factors associated with antiviral prescribing included: antiviral prescribing during the 2009/2010 influenza season, inpatient status, a diagnosis of pneumonia, having a cough, and having an abnormal chest X-ray (Table 2). Multivariable analyses showed that a higher odds of antiviral prescribing was seen during the 2009/2010 influenza season (vs. 2007/2008 influenza season) and in those with a cough, after controlling for other factors (Table 2).
Table 2 .
Factors associated with antiviral prescribing in Veterans with SCI (N = 101)
| Demographic and medical characteristics | Antivirals prescribed |
Unadjusted comparison | Adjusted comparison | |
|---|---|---|---|---|
| Yes | No | |||
| Frequency (%) N = 50 | Frequency (%) N = 51 | OR (95% CI), P-value | OR (95% CI), P-value | |
| Age | ||||
| <50 | 14 (28.0) | 17 (33.3) | Reference | |
| 50–64 | 22 (44.0) | 26 (51.0) | 1.03 (0.41–2.55), 0.95 | |
| 65 and older | 14 (28.0) | 8 (15.7) | 2.13 (0.69–6.51), 0.18 | |
| Race | ||||
| White | 39 (78.0) | 34 (66.7) | Reference | |
| Black | 7 (14.0) | 13 (25.5) | 0.47 (0.17–1.31), 0.14 | |
| Other | 4 (8.0) | 4 (7.8) | 0.87 (0.20–3.75), 0.85 | |
| Hispanic ethnicity | 7 (14.0) | 6 (11.8) | 1.22 (0.38–3.93), 0.74 | |
| Sex | ||||
| Male | 45 (90.0) | 48 (94.1) | Reference | |
| Female | 5 (10.0) | 3 (5.9) | 1.78 (0.40–7.87), 0.44 | |
| Smoking status | ||||
| Never smoked | 15 (30.0) | 17 (33.3) | Reference | |
| Past smoker | 19 (38.0) | 17 (33.3) | 1.34 (0.52–3.46), 0.54 | |
| Current smoker | 16 (32.0) | 16 (31.4) | 1.20 (0.45–3.18), 0.71 | |
| Level | ||||
| Paraplegia | 23 (46.0) | 16 (31.4) | Reference | |
| Tetraplegia | 27 (54.0) | 35 (68.6) | 0.54 (0.24–1.21), 0.13 | |
| ASIA impairment level | ||||
| A | 13 (26.0) | 17 (33.3) | Reference | |
| B | 5 (10.0) | 7 (13.7) | 0.93 (0.24–3.62), 0.92 | |
| C | 5 (10.0) | 2 (3.9) | 3.27 (0.54–19.62), 0.18 | |
| D | 14 (28.0) | 13 (25.5) | 1.41 (0.50–4.00), 0.52 | |
| Missing | 13 (26.0) | 12 (23.5) | 1.41 (0.49–4.12), 0.52 | |
| Duration of injury | ||||
| < 10 years | 14 (28.0) | 12 (23.5) | Reference | |
| 10–20 years | 10 (20.0) | 9 (17.6) | 0.95 (0.29–3.12), 0.94 | |
| > 20 years | 14 (28.0) | 16 (31.4) | 0.75 (0.26–2.15), 0.59 | |
| Missing | 12 (24.0) | 14 (27.5) | 0.73 (0.25–2.19), 0.58 | |
| Received seasonal influenza immunization | 35 (70.0) | 35 (68.6) | 1.07 (0.46–2.49), 0.88 | |
| Received H1N1immunization | 18 (36.0) | 23 (45.1) | 0.68 (0.31–1.52), 0.35 | |
| Inpatient status | 19 (38.0) | 7 (13.7) | 3.85 (1.44–10.27), 0.01 | 1.26 (0.97–1.65), 0.08 |
| Time period | ||||
| 2007/2008* | 13 (26.0) | 22 (43.1) | Reference | Reference |
| 2008/2009* | 14 (28.0) | 18 (35.3) | 1.32 (0.49–3.50), 0.58 | 1.09 (0.88–1.35), 0.44 |
| 2009/2010† | 23 (46.0) | 11 (21.6) | 3.54 (1.31–9.55), 0.01 | 1.29 (1.04–1.61), 0.02 |
| Documented condition other than influenza | ||||
| Upper respiratory infection | 8 (16.0) | 2 (3.9) | 4.67 (0.94–23.19), 0.05 | |
| Bronchitis | 1 (2.0) | 1 (2.0) | 1.02 (0.06–16.77), 0.99 | |
| Pneumonia | 13 (26.0) | 5 (9.8) | 3.23 (1.06–9.89), 0.03 | 0.98 (0.71–1.34), 0.88 |
| Reported symptoms | ||||
| Fever | 35 (70.0) | 26 (51.0) | 2.24 (0.99–5.08), 0.05 | |
| Headache | 10 (20.0) | 13 (25.5) | 0.73 (0.29–1.86), 0.51 | |
| Sore throat | 18 (36.0) | 11 (21.6) | 2.05 (0.85–4.94), 0.11 | |
| Cough | 39 (78.0) | 26 (51.0) | 3.41 (1.43–8.10), 0.01 | 1.23 (1.02–1.50), 0.03 |
| Aches/myalgia | 27 (54.0) | 20 (39.2) | 1.82 (0.83–4.01), 0.14 | |
| Abnormal chest X-ray | 16 (32.0) | 5 (9.8) | 4.32 (1.44–12.98), 0.01 | 1.12 (0.86–1.47), 0.41 |
| Positive influenza culture | 9 (18.0) | 3 (5.9) | 3.51 (0.89–13.84), 0.06 | |
| Severity measure | ||||
| Admitted to ICU | 8 (16.0) | 4 (7.8) | 2.24 (0.63–7.97), 0.21 | |
| Supplemental oxygen | 13 (26.0) | 3 (5.9) | 5.62 (1.49–21.18), 0.01 | |
| Ventilator support | 3 (6.0) | 2 (3.9) | 1.56 (0.25–9.78), 0.63 | |
| Sepsis | 3 (6.0) | 3 (5.9) | 1.02 (0.20–5.32), 0.98 | |
*Time period is 1 October to 30 September.
†Time period is 1 October to 31 May.
Table 3 describes patient and medical factors associated with appropriate antiviral prescribing in veterans with SCI/D. In bivariate analyses, having a fever, aches/myalgia, and/or having a positive influenza test were associated with receipt of appropriate antiviral treatment. Time period did not achieve statistical significance at the 0.05 level. After multivariable adjustment, the same factors were associated with appropriate prescribing (Table 3).
Table 3 .
Factors associated with appropriateness of antiviral treatment in Veterans with SCI (N = 101)
| Demographic and medical characteristics | Antiviral prescribed appropriately |
Unadjusted comparison | Adjusted comparison | |
|---|---|---|---|---|
| Yes | No | |||
| Frequency (%) N = 29 | Frequency (%) N = 72 | OR (95% CI), P-value | OR (95% CI), P-value | |
| Age group | ||||
| < 50 | 11 (37.9) | 20 (27.8) | Reference | |
| 50–64 | 12 (41.4) | 36 (50.0) | 0.61 (0.23–1.62), 0.32 | |
| 65 and older | 6 (20.7) | 16 (22.2) | 0.68 (0.21–2.25), 0.53 | |
| Race | ||||
| White | 20 (69.0) | 53 (73.6) | Reference | |
| Black | 6 (20.7) | 14 (19.45) | 1.14 (0.38–3.36), 0.82 | |
| Other | 3 (10.3) | 5 (6.9) | 1.59 (0.35–7.28), 0.55 | |
| Hispanic ethnicity | 4 (13.8) | 9 (12.5) | 1.12 (0.32–3.97), 0.86 | |
| Sex | ||||
| Male | 27 (93.1) | 66 (91.7) | Reference | |
| Female | 2 (6.9) | 6 (8.3) | 0.81 (0.15–4.29), 0.81 | |
| Smoking status | ||||
| Never smoked | 9 (31.0) | 24 (33.3) | Reference | |
| Past smoker | 11 (38.0) | 25 (34.7) | 1.17 (0.41–3.33), 0.76 | |
| Current smoker | 9 (31.0) | 23 (32.0) | 1.04 (0.35–3.09), 0.94 | |
| Level | ||||
| Paraplegia | 15 (51.7) | 24 (33.3) | Reference | |
| Tetraplegia | 14 (48.3) | 48 (66.7) | 0.47 (0.19–1.12), 0.09 | |
| ASIA impairment level | ||||
| A | 9 (31.0) | 21 (29.2) | Reference | |
| B | 4 (13.8) | 8 (11.1) | 1.17 (0.28–4.88), 0.83 | |
| C | 1 (3.5) | 6 (8.3) | 0.39 (0.04–3.71), 0.40 | |
| D | 6 (20.7) | 21 (29.2) | 0.67 (0.20–2.21), 0.51 | |
| Missing | 9 (31.0) | 16 (22.2) | 1.31 (0.42–4.06), 0.64 | |
| Duration of injury | ||||
| < 10 years | 5 (17.2) | 21 (29.2) | Reference | |
| 10–20 years | 7 (24.1) | 12 (16.7) | 2.45 (0.64–9.44), 0.19 | |
| > 20 years | 10 (34.5) | 20 (27.8) | 2.10 (0.61–7.23), 0.24 | |
| Missing | 7 (24.2) | 19 (26.3) | 1.55 (0.42–5.70), 0.51 | |
| Received seasonal influenza | ||||
| Immunization | 22 (75.9) | 48 (66.7) | 1.57 (0.59–4.19), 0.37 | |
| Received H1N1immunization | 12 (41. 4) | 29 (40.3) | 1.05 (0.44–2.51), 0.92 | |
| Inpatient status | 8 (27.6) | 18 (25.0) | 1.14 (0.43–3.03), 0.79 | |
| Time period | ||||
| 2007/2008* | 7 (24.1) | 28 (38.9) | Reference | Reference |
| 2008/2009* | 8 (27.6) | 24 (33.3) | 1.33 (0.42–4.22), 0.62 | 1.10 (0.95–1.28), 0.20 |
| 2009/2010† | 14 (48.3) | 20 (27.8) | 2.80 (0.96–8.19), 0.06 | 1.10 (0.92–1.32), 0.30 |
| Other documented respiratory diagnoses | ||||
| Upper respiratory infection | 5 (17.2) | 5 (6.9) | 2.79 (0.74–10.50), 0.12 | |
| Bronchitis | 1 (3.4) | 1 (1.4) | 2.54 (0.15–41.95), 0.50 | |
| Pneumonia | 6 (20.7) | 12 (16.7) | 1.30 (0.44–3.89), 0.63 | |
| Reported symptoms | ||||
| Fever | 27 (93.1) | 34 (47.2) | 15.09 (3.34–68.23), <0.01 | 1.38 (1.21–1.57), <0.01 |
| Headache | 8 (27.6) | 15 (20.8) | 1.45 (0.54–3.91), 0.46 | |
| Sore throat | 12 (41.4) | 17 (23.6) | 2.28 (0.91–5.72), 0.07 | |
| Cough | 23 (79.3) | 42 (58.3) | 2.74 (0.99–7.54), 0.05 | |
| Aches/myalgia | 20 (69.0) | 27 (37.5) | 3.70 (1.48–9.29), <0.01 | 1.26 (1.09–1.45), <0.01 |
| Abnormal chest X-ray | 7 (24.1) | 14 (19.4) | 1.32 (0.47–3.70), 0.60 | |
| Positive influenza test | 9 (31.0) | 3 (4.2) | 10.35 (2.56–41.90), <0.01 | 1.62 (1.22–2.14), <0.01 |
| Severity measures | ||||
| Admitted to ICU | 1 (3.4) | 11 (15.3) | 0.20 (0.02–1.61), 0.10 | |
| Given supplemental oxygen | 6 (20.7) | 10 (13.9) | 1.62 (0.53–4.95), 0.40 | |
| Ventilator support | 1 (3.4) | 4 (5.6) | 0.61 (0.07–5.68), 0.66 | |
| Sepsis | 1 (3.5) | 5 (6.9) | 0.47 (0.05–4.28), 0.50 | |
*Time period is 1 October to 30 September.
†Time period is 1 October to 31 May.
Characteristics associated with appropriate antiviral prescribing in multivariable analyses differed in the non-SCI control sample (not shown in table). Compared to those <50 years of age, the 50–64 age group were less likely to receive appropriate antiviral prescribing (P = 0.006). In addition, the later time period (2009/2010) was associated with a higher odds of receiving appropriate treatment (P = 0.04). Having a positive influenza test was also associated with appropriate antiviral prescribing (P = 0.0004) (not shown in table).
A conditional multiple logistic regression model including both the SCI/D and non-SCI/D control sample showed that having SCI/D was an independent predictor of receiving antiviral treatment (adjusted odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.04–1.29, P = 0.008) after controlling for age, race, other respiratory illness diagnoses, vaccination, symptoms, and testing. However, a similar conditional multiple logistic regression model found that SCI/D was not associated with receiving appropriate antiviral treatment (adjusted OR = 0.90, 95% CI 0.58–1.39, P = 0.62).
Discussion
Prescription of antivirals for treatment of influenza in Veterans with SCI/D has increased over the past few years (37.1% in 2007/2008 to 67.6% in 2009/2010). An earlier study showed that antiviral treatment was rarely used by practitioners treating patients with SCI/D, which may have been due to persons with SCI/D not contacting their practitioner in time for effective use of antivirals because of their limited mobility and/or due to late onset or lack of influenza symptoms.16 Furthermore, recent research found that among patient groups at high risk for influenza complications (including patients with disabilities and patients 65 years of age or older), self-reported ILI was greater but receipt of antiviral treatment was not, despite guidelines that recommend use in these cohorts.17 In this study, prescribing of antivirals was higher in those with SCI/D compared to the non-SCI/D control sample of Veterans; but still lower than what has been reported in the literature for the general patient population.18 However, the increase in use of antivirals overall as well as the onset of the H1N1 pandemic suggests that providers treating patients with SCI/D are adhering more to the CDC recommendations for use of antivirals.10 In fact, the influenza season following the start of the H1N1 epidemic saw a 3.5 times increase in the odds of antiviral prescribing compared to the season prior to the H1N1 pandemic (2007/2008). Similar increases in antiviral prescribing during the pandemic season were shown in the CDC Emerging Infections Program data and in other literature.18–19
The clinical factors associated with antiviral prescribing were not surprising. Factors included being an inpatient, having an abnormal chest X-ray, having a diagnosis of pneumonia, or a cough; although cough was the only variable to remain statistically significant in multivariable analyses. Similar clinical factors have been shown to be associated with antiviral prescribing in other studies and populations.13,18,20 The timing of administration can be a significant barrier to providing antivirals since it is recommended that treatment start within 48 hours of symptom development.21 In fact, we found a moderate increase in appropriateness of treatment in this population over time (20.0–41.2%), where in those who actually received an antiviral, a little over half were treated appropriately. A common reason for inappropriate use of an antiviral was that patients had experienced influenza symptoms for more than 2 days, similar to findings by Linder et al.15 However, the most frequent reason for inappropriate antiviral prescribing was that patients did not have a fever and/or at least two of other symptoms (headache, sore throat, cough, or myalgia). We hypothesize that reliance on symptom criteria may be a limitation in this patient population because weak respiratory muscles due to higher level injuries result in impaired cough.18 Patients with SCI/D may be less likely to present with cough as a result.22
Study limitations
There are several limitations to this study including that it was retrospective review of medical datasets and records, which may have had incomplete or missing data for some characteristics. In addition, due to the rare use of influenza testing and the miscoding found for influenza or ILI diagnosis, this study may have underestimated the number of veterans with SCI/D who had influenza. However, we used a similar methodology to Linder et al.,15 using clinician documentation of influenza to identify the sample, potentially overestimating the number of true influenza cases. On the other hand, patients who did not visit a VA medical care facility or did not have severe illness would be undercounted in our sample.
In addition, we assessed data outside the traditional influenza season (after March/April) due to the unique timing of the H1N1 pandemic, which occurred after traditional influenza season. However, we did find that all of our influenza cases occurred during the traditional influenza season (October to April) except during the H1N1 pandemic.
Although having a SCI/D (compared to not having SCI/D) was a significant predictor of receiving an antiviral, the appropriateness of treatment did not significantly differ between the two groups. This suggests that providers who treat patients with SCI/D recognize that they are an important at-risk patient population for influenza complications. Further efforts to work with providers as to when antiviral prescribing is appropriate are warranted, such as implementation of clinical reminders to guide appropriate treatment.23 Appropriate treatment of patients with influenza depends on accurate and timely diagnosis; which could be improved through rapid influenza testing.24 In addition, discussion as to whether cough is a valid symptom for influenza in SCI/D should also be considered.
Disclaimer statements
Contributors All authors have provided significant contributions to the preparation of this research and drafting this manuscript.
Funding This material is based on the work supported by the Office of Research and Development, Health Services Research and Development, and Spinal Cord Injury Quality Enhancement Research Initiative of the Department of Veterans Affairs (Project Number: RRP 10-046).
Conflicts of interest CTE received funding as an investigator from Merck. That funding was unrelated to the proposed manuscript. All other authors have no conflicts to report.
Ethics approval This research was approved by the local Institution Review Board.
References
- 1.Centers for Disease Control and Prevention. Seasonal influenza (Flu): people at high risk for developing flu-related complications [document on the Internet]. 2013 [accessed 2013 May 5]. Available from: http://www.cdc.gov/flu/about/disease/high_risk.htm.
- 2.Winslow C, Rozovsky J. Effect of spinal cord injury on the respiratory system. Am J Phys Med Rehabil 2003;82(10):803–14. [DOI] [PubMed] [Google Scholar]
- 3.Weaver FM, Smith B, Evans CT, Kurichi JE, Patel N, Kapur VK, et al. Outcomes of outpatient visits for acute respiratory illness in veterans with spinal cord injuries and disorders. Am J Phys Med Rehabil 2006;85(9):718–26. [DOI] [PubMed] [Google Scholar]
- 4.Smith BM, Evans CT, Kurichi JE, Weaver FM, Patel N, Burns SP. Acute respiratory tract infection visits of veterans with spinal cord injuries and disorders: rates, trends, and risk factors. J Spinal Cord Med 2007;30(4):355–61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001–02. Vital Health Stat 13 2006;159:1–66. [PubMed] [Google Scholar]
- 6.Ciesla G, Leader S, Stoddard J. Antibiotic prescribing rates in the US ambulatory care setting for patients diagnosed with influenza, 1997–2001. Respir Med 2004;98(11):1093–101. [DOI] [PubMed] [Google Scholar]
- 7.DeVivo MJ, Black KJ, Stover SL. Causes of death during the first 12 years after spinal cord injury. Arch Phys Med Rehabil 1993;74(3):248–54. [PubMed] [Google Scholar]
- 8.Centers for Disease Control and Prevention. Morbidity and mortality weekly report: prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010 [document on the Internet]. 2010 [accessed 2011 August 18]. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm?s_cid=rr5908a1_e.
- 9.Cox NJ, Subbarao K. Influenza. Lancet 1999;354(9186):1277–82. [DOI] [PubMed] [Google Scholar]
- 10.Centers for Disease Control and Prevention. Seasonal influenza (flu): use of antivirals, guidance on the use of influenza antiviral agents [document on the Internet]. 2014 [accessed 2013 April 7]. Available from: http://www.cdc.gov/flu/professionals/antivirals/antiviral-use-influenza.htm.
- 11.Centers for Disease Control and Prevention. H1N1 flu: updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009–2010 season [document on the Internet]. 2009 [accessed 2013 May 5]. Available from: http://www.cdc.gov/h1n1flu/recommendations.htm.
- 12.VIReC Research User Guide: FY2002 VHA Medical SAS® Inpatient Datasets. Edward J. Hines, Jr. VA Hospital, Hines, IL: Veterans Affairs Information Resource Center, April 2003a. [Google Scholar]
- 13.VIReC Research User Guide: FY2002 VHA Medical SAS® Outpatient Datasets. Edward J. Hines, Jr. VA Hospital, Hines, IL: Veterans Affairs Information Resource Center, January 2003b. [Google Scholar]
- 14.El Masry WS, Tsubo M, Katoh S, El Miligui YH, Khan A. Validation of the American Spinal Injury Association (ASIA) motor score and the National Acute Spinal Cord Injury Study (NASCIS) motor score. Spine 1996;21(5):614–9. [DOI] [PubMed] [Google Scholar]
- 15.Linder JA, Nieva HR, Blumentals WA. Antiviral and antibiotic prescribing for influenza in primary care. J Gen Intern Med 2009;24(4):504–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Evans CT, Lavela SL, Smith B, Miskevics S, Weaver FM, Goldstein B. Influenza diagnosis and treatment in veterans with spinal cord injury. Arch Phys Med Rehabil 2006;87(2):291–3. [DOI] [PubMed] [Google Scholar]
- 17.Biggerstaff M, Jhung MA, Reed C, Garg S, Balluz L, Fry AM, et al. Impact of medical and behavioural factors on influenza-like illness, healthcare-seeking, and antiviral treatment during the 2009 H1N1 pandemic: USA, 2009–2010. Epidemiol Infect 2014;142(1):114–25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Doshi S, Kamimoto L, Finelli L, Perez A, Reingold A, Gershman K, et al. Description of antiviral treatment among adults hospitalized with influenza before and during the 2009 pandemic: United States, 2005–2009. J Infect Dis 2011;204(12):1848–56. [DOI] [PubMed] [Google Scholar]
- 19.Greene SK, Shay DK, Yin R, McCarthy NL, Baxter R, Jackson ML, et al. Patterns in influenza antiviral medication use before and during the 2009 H1N1 pandemic, Vaccine Safety Datalink Project, 2000–2010. Influenza Other Respir Viruses 2012;6(6):e143–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Linder JA, Chan JC, Bates DW. Appropriateness of antiviral prescribing for influenza in primary care: a retrospective analysis. J Clin Pharm Ther 2006;31(3):245–52. [DOI] [PubMed] [Google Scholar]
- 21.Couch RB. Influenza: prospects for control. Ann Intern Med 2000;133(12):992–8. [DOI] [PubMed] [Google Scholar]
- 22.Brown R, DiMarco AF, Hoit JD, Garshick E. Respiratory dysfunction and management in spinal cord injury. Respir Care 2006;51(8):853–70. [PMC free article] [PubMed] [Google Scholar]
- 23.Wilkes JJ, Zaoutis TE, Keren R, Desai B, Leckerman KH, Hodinka RL, et al. Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: review of five seasons and evaluation of an electronic reminder. J Hosp Med 2009;4(3):171–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Centers for Disease Control and Prevention. Seasonal influenza (flu): influenza symptoms and the role of laboratory diagnostics [document on the Internet]. 2011 [accessed 2013 May 9]. Available from: http://www.cdc.gov/flu/professionals/diagnosis/labrolesprocedures.htm.