Low back pain in general practice: cost-effectiveness of a minimal psychosocial intervention versus usual care

An intervention that can prevent low back pain (LBP) becoming chronic, may not only prevent great discomfort for patients, but also save substantial costs for the society. Psychosocial factors appear to be of importance in the transition of acute to chronic LBP. The aim of this study was to compare the cost-effectiveness of an intervention aimed at psychosocial factors to usual care in patients with (sub)acute LBP. The study design was an economic evaluation alongside a cluster-randomized controlled trial, conducted from a societal perspective with a follow-up of 1 year. Sixty general practitioners in 41 general practices recruited 314 patients with non-specific LBP of less than 12 weeks’ duration. General practitioners in the minimal intervention strategy (MIS) group explored and discussed psychosocial prognostic factors. Usual care (UC) was not protocolized. Clinical outcomes were functional disability (Roland–Morris Disability Questionnaire), perceived recovery and health-related quality of life (EuroQol). Cost data consisted of direct and indirect costs and were measured by patient cost diaries and general practitioner registration forms. Complete cost data were available for 80% of the patients. Differences in clinical outcomes between both the groups were small and not statistically significant. Differences in cost data were in favor of MIS. However, the complete case analysis and the sensitivity analyses with imputed cost data were inconsistent with regard to the statistical significance of this difference in cost data. This study presents conflicting points of view regarding the cost-effectiveness of MIS. We conclude that (Dutch) general practitioners, as yet, should not replace their usual care by this new intervention.
Introduction
Low back pain (LBP) affects a large number of people each year. Lifetime prevalence rates range from 49 to 70% [45]. LBP causes not only great discomfort, but also great economic loss due to work absenteeism [28, 45]. In the UK, LBP is one of the most expensive conditions for which an economic analysis has been carried out [28]. Economic evaluations in which both the costs and clinical outcomes of two or more interventions are compared, are becoming increasingly important, as health care expenditures rise while budgets remain limited [44]. The importance of economic evaluations is illustrated by the fact that some authors suggest that an intervention might be implemented when it is less effective but saves substantial costs [8].
As especially chronic LBP is associated with substantial costs to society [15], a large amount of costs can be saved by interventions that prevent acute LBP becoming chronic. The rationale is that it will be more cost-effective to address a wider target population early with simple low-cost interventions than to expend considerable time and resources on rehabilitating the smaller group of back pain patients who have become incapacitated by chronic pain. As psychosocial factors have been shown to play an important role in the transition from acute to chronic back pain [25, 33], one may assume that early interventions focusing on these factors prevent chronicity.
We tested this assumption by conducting a cluster-randomized clinical trial in general practice, comparing a minimal intervention strategy (MIS) aimed at psychosocial factors for patients with (sub)acute LBP to usual care (UC) by the GP, which was not standardized. Our theory on the working mechanisms of MIS was that identification and discussion of psychosocial factors would lead to modification of these factors, eventually leading to better functioning. Unfortunately, MIS appeared to be no more effective than UC in improving the following clinical outcomes: the degree of functional disability, the recovery rate and the number of patients on sick-leave due to LBP [20]. These findings are in line with Linton and Andersson [26], who showed that their cognitive-behavioral intervention was not more effective than usual care in reducing the degree of back pain and generic function status. However, their intervention was effective in reducing the number of visits to a physician for spinal pain and number of days of sick-leave, implicating time savings for physicians and thus substantial cost savings for society. These results may indicate an increase in coping or self-care with the pain; patients who received the psychosocial intervention, less often visited a physician and had less days of work while they had the same degree of functional disability as the patients who received usual care. These promising results, in combination with the fact that self-care with the pain was also a goal in our MIS, the recent emphasis on health care budgets, and the call for more high quality economic evaluations on the cost-effectiveness of treatments for LBP [43] stimulated us to conduct an economic evaluation from a societal perspective with a follow-up of 1 year. We hypothesized that MIS would be cost-effective compared to UC.
Materials and methods
Study design
The study is designed as a full economic evaluation alongside a cluster-randomized controlled trial and was approved by the Medical Ethics Committee of the VU University Medical Center in Amsterdam, the Netherlands.
Randomization and training sessions
Randomization took place at the level of the general practice in blocks of four practices, according to a random numbers table prepared before recruitment of general practitioners. General practitioners were informed about their allocation after they had given final consent to participation. Twenty practices (28 GPs) were randomized to the MIS group and 21 practices (32 GPs) to the UC group. The GPs randomized to the MIS group received two training sessions of 2.5 h each which were given by a GP (HvdH) with extensive expertise in development and training of psychosocial interventions. The training consisted of theory, role-playing and feedback on the practiced skills. In addition, a treatment manual was provided. The contents of the training sessions and its evaluation by GPs have been described in more detail elsewhere [21].
Patients and interventions
Participating GPs were asked to select ten consecutive patients who consulted them for LBP. Inclusion criteria were age 18–65, non-specific LBP of less than 12 weeks’ duration (i.e. (sub)acute LBP) or an exacerbation of mild symptoms, and sufficient knowledge of the Dutch language. Exclusion criteria were specific LBP (i.e. LBP caused by specific pathological conditions), LBP currently treated by another healthcare professional, and pregnancy. Patients, but not their GPs, were kept unaware that two different interventions were studied.
Patients received a minimal intervention strategy (MIS) or usual care (UC). The MIS was aimed at identification and discussion of psychosocial prognostic factors. The MIS consultation lasted about 20 min and consisted of three phases: exploration, information and self care. During the exploration phase, the GP explored the presence of psychosocial prognostic factors by asking standardized questions that could be rephrased to fit the style of communication of the doctor and the patient. The following psychosocial prognostic factors were explored: the patient’s own ideas on the cause of their LBP, fear avoidance beliefs, worries/distress, pain catastrophising, pain behaviors and reactions from the social environment (family, friends, work). In the information phase the GP provided general information on the cause, course and (im)possibilities of treatment of LBP, thereby giving specific attention to psychosocial factors identified in the exploration phase. Finally, in the self care phase, the GP and patient set specific goals on resuming activities or work. Follow-up consultations were not protocolized, but we advised GPs to make an appointment for a follow-up visit in case they identified obstacles to recovery and suspected an increased risk of chronic LBP.
GPs in the UC group provided care as usual. We did not protocolize the content and number of UC consultations, and assumed that GPs would generally follow the guideline for LBP of the Dutch College of General Practitioners [13]. For acute LBP (<6 weeks’ duration) this guideline advises a wait and see policy. For subacute LBP (6–12 weeks’ duration) the guideline advises referral for physical therapy in the case of persistent functional disability. Explicit guidance on psychosocial factors is lacking. The contents of both interventions have been described in more detail elsewhere [20].
Data collection
Clinical outcomes
Baseline data were collected during a home visit by a research assistant, while follow-up data after 12 months were collected using postal questionnaires. Primary clinical outcome measures were functional disability, perceived recovery, and health related quality of life. Functional disability was measured at baseline and after 12 months by the Roland–Morris disability questionnaire (0–24) [35]. Perceived recovery was scored by the patient on a 7-point Likert scale (very much/much/slightly improved, no change, slightly/much/very much worse) after 12 months [42]. As a score of at least “much improved” has been denoted a minimal clinically important change [32], patients were a priori defined as recovered if they reported at least “much improvement”. Health related quality of life was measured at baseline and after 3, 6 and 12 months by the EuroQol (0–1) [12], covering five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EuroQol scores were transformed into utilities using a representative British sample and time trade-off methods. The utilities were then multiplied by the amount of time a patient spent in this particular health state, with transitions between health states linearly interpolated [7]. This results in quality adjusted life years (QALYs).
In order to describe the study population characteristics in more detail and to compare baseline similarity of both intervention groups, five other outcome measures were assessed at baseline: (1) pain severity during the day (0–10) [27]; (2) perceived general health (1–5), using the first question of the subscale “general health perceptions” of the short form health survey (SF-36) [47]; (3) fear avoidance beliefs, using the 4-item physical activity subscale of the fear avoidance beliefs questionnaire (FABQ, 0–24) [46]; (4) catastrophising thoughts, using the 6-item subscale of the coping strategies questionnaire (CSQ, 0–36) [36] and (5) distress, measured by the 16-item subscale of the four-dimensional symptom questionnaire (4DSQ, 0–32) [37].
Cost data
The economic evaluation was conducted from a societal perspective, indicating that all costs and consequences of the competing interventions are taken into account regardless of who pays for or benefits from them [9]. A societal perspective incorporates direct health care costs, direct non-health care costs and indirect costs due to LBP. All cost data were collected by prospective cost diaries [16] that patients completed for the periods baseline to 3 months, 3–6 months, 6–9 months, and 9–12 months. In addition, GPs were contacted after 12 months follow-up to provide information on follow-up consultations due to LBP in the last year (date, referrals, medication prescribed by physician). GPs used their medical records to complete these registration forms.
Table 1 summarizes the cost categories, and the prices and sources used for valuing. “Medication” in Table 1 includes both the over-the-counter medication and medication prescribed by physicians, while self-prescribed alternative interventions are included in “complementary care”. Costs of absenteeism from paid labor due to LBP were calculated according to the friction cost approach [23]. This approach is based on a mean income of the Dutch population according to age and gender, and defines a friction period as 154 days [31]. As most cost data were collected during the year 2002, prices were adjusted using consumer price index figures.
Table 1Prices used for valuing resources (year 2002)ResourcesEuroDirect health care Primary care costs  General practitioner (consultation)a19.8  MIS-consultation, including intervention costs (consultation)b40.9  Physical therapist (treatment session)a22.3  Manual therapist (treatment session)c30.8  Exercise therapist (treatment session)a22.5  Back school (treatment session) [18]66.3  Chiropractor (treatment session)d40.0  Physiofitness (treatment program, 10 sessions)b120.0  Professional homecare (per hour)a21.3  Psychologist (treatment session)d75.0 Secondary care costs  Outpatient appointmenta54.8  Hospitalization general hospital (per day)a330.0  Surgery (per hour)b884.7  Radiographb48.2  MRI-scanb212.9 MedicationeDirect non-health care  Complementary care d  Informal care (per hour)a8.1  Equipment aidsfIndirect costsAbsenteeism from paid workgAbsenteeism from unpaid worka8.1MIS Minimal intervention strategy, MRI Magnetic resonance imagingaPrice according to Dutch guidelines [30]bCalculated unit costscPrice according Dutch Central Organisation for Health Care Charges [10]dPrice according to professional organisation or health care providerePrice of medication prescribed by the GP according to Royal Dutch Society for Pharmacy [48]; price of over-the-counter medication according to cost diariesfPrice according to cost diariesgCosts based on mean income of Dutch population according to age and sex [23, 31]
Statistical analysis
Firstly, baseline similarity was studied. Secondly, we compared baseline characteristics of patients with complete cost data to those with incomplete cost data by using logistic regression analysis. Thirdly, clinical outcomes and total costs were compared. As cost data are characterized by large variation and irregular distributions and as a complete cost dataset was available for 80% of our participants (250/314), we decided that our primary analysis would be a complete case analysis. Differences between groups (MIS minus UC) were calculated for the clinical outcomes: (1) functional disability, by calculating change scores between baseline and 12 months follow-up; (2) perceived recovery at 12 months follow-up; and (3) health-related quality of life gained over 12 months (i.e. QALYs). Students t tests were used to analyze the change scores between the treatment groups for functional disability and quality of life, and a Chi-square test for perceived recovery. To compare costs between the two groups, confidence intervals (CIs) for the mean differences in costs were calculated using bias-corrected and accelerated bootstrapping (2000 replications) [11]. Bootstrapping incorporates drawing samples with replacement and is a preferred method for the analysis of cost data, as it uses the observed distributions of the data without making assumptions about the shape of the distribution [38]. Fourthly, cost-effectiveness analyses were performed. Incremental cost-effectiveness ratios were calculated in which the mean difference in total costs (MIS minus UC) was divided by the mean difference in improvement on the clinical outcomes (MIS minus UC). Uncertainty around the ratios was calculated using the bias-corrected percentile bootstrapping method (5,000 replications) [5] and plotted on a cost-effectiveness plane.
Sensitivity analyses
A complete case analysis has some disadvantages. Due to the missing data the power of the analysis is reduced and bias may be introduced due to selective drop-out. Imputation can be used to replace missing data by statistical estimates of the missing values. To explore the robustness of our primary analysis, we performed two sensitivity analyses in which we imputed missing data: in one analysis we imputed all missing cost data, and in the other we imputed only missing days of absenteeism. Imputation was done using the Expectation Maximization algorithm (SPSS 10.1).
Results
Between September 2001 and April 2003, 314 patients were enrolled in our study: 143 in the MIS group and 171 in the UC group. Table 2 shows that baseline characteristics of GPs and patients were largely similar for the two groups. Less than 9% of all patients withdrew from the study during follow-up. Reasons were ‘no time and no complaints anymore’ (MIS n = 1, UC n = 4), “burden too high due to psychological problems” (UC n = 3) or “unknown” (MIS n = 10; UC n = 8). The flow chart of this study, including information on refusals, exclusions and drop-outs has been published in our previous paper [20].
Table 2Baseline characteristics of general practitioners and patientsMIS UC GPsn = 28n = 32Demographic characteristics Age (years)a, mean (SD)43.0 (7.2)45.7 (7.4) Gender, female6/2812/32Number of included patients per GP 0 1/285/32 1–517/2814/32 >5 10/28 13/32Patientsn = 143n = 171Demographic characteristics Age (years), mean (SD)43.4 (11.1)42.0 (12.0) Gender, % female47.647.4 Nationality, % Dutch97.297.7 Health insurance, % public70.667.8Educational level and work status Education levela, %  Primary35.0 33.1  Secondary46.252.7  College, university 18.814.2 Paid job, % yes81.881.3 Sick leave because of LBPa (among the working population), % yes34.841.0Characteristics of LBP Duration current episode (days), median (IQR)11 (5–21)14 (7–21) Frequency of LBP episodes last year, %  1 or 2 episodes58.060.8  3 or more episodes 19.618.7  Exacerbation of persisting LBP22.420.5 Pain radiating below kneea, %12.814.6Clinical outcomes, primary measures Functional disability (RDQ, 0–24), mean (SD)11.7 (5.4)12.2 (5.0) Health related quality of life (EuroQol), mean (SD)0.61 (0.25)0.61 (0.24)Clinical outcomes, secondary measures  Pain severity during the day (0–10)b, mean (SD)4.9 (2.0)4.8 (2.0) Severity of the main complaint (0–10)a, mean (SD)7.0 (1.9)6.8 (2.0) Perceived general health (SF-36, 1–5)a, mean (SD)2.7 (0.8)2.8 (0.8)Clinical outcomes, psychosocial measures  Fear-avoidance beliefs (FABQ, 0–24), mean (SD)14.3 (5.6)15.3 (5.2) Catastrophising thoughts (CSQ, 0–36), mean (SD)10.3 (6.6)11.2 (6.9) Distress (4DSQ, 0–32)b, mean (SD)8.3 (7.0) 9.5 (7.3)GP General practitioner, MIS Minimal intervention strategy, UC Usual care, n number, SD Standard deviation, IQR Inter quartile range (25th–75th percentile), LBP Low back pain, RDQ Roland–Morris disability Questionnaire, SF-36 Short-form 36, FABQ Fear avoidance and beliefs questionnaire, CSQ Coping strategies questionnaire, 4DSQ 4D symptom questionnaire (higher scores means more functional disability, worse health, more fear-avoidance, more catastrophising or more distress)aTwo missing valuesbOne missing value
For 116 patients (81%) in the MIS group and 134 patients (78%) in the UC group complete cost data were available. Logistic regression analysis comparing baseline characteristics of patients with complete cost data to those with incomplete cost data showed that patients with incomplete cost data on average were younger and scored higher on distress at baseline.
Clinical outcomes
After 1 year follow-up both the groups showed similar improvements in clinical outcomes. Sixty-nine percent of the patients were defined as recovered after 1 year. The difference between both the groups in mean improvement on functional disability was −0.74 points on the RDQ (95% CI, −2.31 to 0.83), and −2% (95% CI, −14 to 10%) on recovery rate. Over the follow-up period of 1 year the mean difference in quality of life was 0.004 QALYs (95% CI, −0.04 to 0.03). All differences favored UC, but were neither clinically relevant nor statistically significant (Table 5).
Cost data
Table 3 lists per patient the mean utilization of resources (i.e. health care, help, absenteeism). In both the groups, resource utilization was low and largely similar. Only two statistically significant differences were found. In the year following randomization patients in the MIS group had more consultations with a GP (MIS 2.7 vs. UC 0.9), excluding the consultation leading to recruitment but including the 20 min consultation aimed at psychosocial measures as specified by the study protocol. Patients in the UC group reported more consultations with a manual therapist (MIS 0.1 vs. UC 0.4) but the proportions of patients who received such a treatment (MIS 2.6% vs. UC 9%) were very low.
Table 3Mean resource use (SD) per patient (n = 250) for MIS and UC during 12 months follow-up, and the percentage of patients who made use of that specific resourceResourcesMIS (n = 116)UC (n = 134)Direct health care  Primary care  General practitioner (consultations)*2.7 (1.0)99.1%0.9 (1.2)44%  Physical therapy (treatment sessions)2.3 (5.8)17.2%3.2 (5.8)35.1%  Manual therapy (treatment sessions)*0.1 (0.7)2.6%0.4 (1.7)9%  Exercise therapy (treatment sessions)0.3 (1.8)2.6%0.9 (3.5)9%  Back school (treatment sessions)0.5 (0.6)0.9%0 (0)0%  Chiropractor (treatment sessions)0 (0)0%0.1 (0.9)2.2%  Physiofitness (treatment programs)0.1 (0.2)6%0.1 (0.2)4.5%  Professional home care (hours)0 (0)0%0.6 (6.5)0.7%  Psychologist (treatment sessions)0.1 (0.8)0.9%0 (0)0% Secondary care  Outpatient visit (number)0.1 (0.4)4.3%0.2 (0.7)7.5%  Hospitalization (days)0.02 (0.2)0.9%0.01 (0.1)0.7%  X-ray (number)0.1 (0.3)5.2%0.1 (0.4)9.7%  MRI-scan (number)0.01 (0.1)0.9%0.03 (0.2)2.2%  Medication (% yes)–74.1%–73.9%Direct non-health care Complementary care  Homeopathy (treatment sessions)0.04 (0.3)1.7%0 (0)0%  Osteopathy (treatment sessions)0.1 (0.5)3.4%0.2 (0.3)0.7%  Massage (treatment sessions)0.1 (0.8)1.7%0.4 (3.0)3.7%  Acupuncture (treatment sessions)0 (0)0%0.04 (0.4)1.5%  Magnetizer (treatment sessions)0.3 (2.3)1.7%0.1 (1.0)0.7% Orthomanual therapy (treatment sessions)0.03 (0.3)1.7%0.03 (0.4)0.7%  Podiatrist 0.03 (0.2)1.7%0.03 (0.3)1.5%  Informal care (hours)0 (0)0%0.7 (6.3)3%  Equipment aids (% yes)–10.3%–6.0%Indirect costs  Absenteeism paid work (days)4.2 (12.1)28.4%8.6 (23.1)38.8%  Absenteeism unpaid work (hours)2.2 (10.9)12.1%3.3 (10.4)17.2%*Significant difference (P < 0.05)SD Standard deviation, n number, MIS Minimal intervention strategy, UC Usual care
Table 4 shows the mean total costs in both the treatment groups and the difference in costs with 95% CI. Total indirect costs, especially absenteeism from paid work, were the largest contributor to the total costs. The difference in total costs amounted to 490 € (95% CI −987 to 92 €) in favor of the MIS group (MIS 799 €; UC 1288 €), but this difference was not statistically significant.
Table 4Mean costs (SD) in Euros per patient in the MIS and UC group and differences between both the groups during follow-up of 52 weeksMIS (n = 116)UC (n = 134)Mean difference (95% CI)Direct health care costs181 (287)175 (275)6 (−65; 73) Primary care costs159 (181)152 (242)7 (−52; 54) Secondary care costs22 (179)23 (101)−1 (−44; 35) Medication costs9 (18)9 (14)0 (−4; 4)Direct non-health care costs30 (75)31 (129)−1 (−25 ; 27) Complementary care costs18 (65)21 (115)−2 (−24; 22) Informal care6 (34)8 (58)−2 (−12; 11) Equipment aids5 (22)2 (14)3 (−2; 6)Indirect costs587 (1,636)1,081 (2,463)−495 (−921; 158) Absenteeism paid work569 (1,631)1,055 (2,448)−486 (−932; 50) Absenteeism unpaid work18 (89)27 (84)−9 (−31; 18)Total costs798 (1,820)1,288 (2,594)−490 (−987; 92)None of the mean differences between MIS and UC are statistically significant (P > 0.05)SD Standard deviation, MIS Minimal intervention strategy, UC Usual care, n Number, 95% CI 95% confidence interval
Cost-effectiveness
Table 5 shows the incremental cost-effectiveness ratios (ICERs) for the three outcome measures. MIS resulted in less improvement than UC, but saved money. The ICER for functioning was 690 €, indicating that per point less improvement on the RDQ MIS saved 690 €, while per percent less improvement in recovery rate MIS saved 239 €. The difference in QALY’s gained during 1 year between both the groups was very small, resulting in a large ICER of 47,348 €. The large majority of the bootstrapped ICERs presented on the cost-effectiveness planes are located in the southern quadrants (Fig. 1), indicating that the costs of MIS were lower than the costs of UC.
Table 5Incremental cost-effectiveness ratios for functional disability, perceived recovery and health-related quality of lifeOutcome measureMISUCMIS versus UCCostsEffectsaCostsEffectsaICERFunctional disability (RDQ; 0–24) Change score between baseline and 1 year follow-up798 € (n = 116)8.378 (n = 116)1,307 € (n = 132)9.116 (n = 132)MIS results in less improvement, but saves 690 € per RDQ pointRecovery rate Score at 1 year follow-up 798 € (n = 116)68.1% (n = 116)1,288 € (n = 134)70.1% (n = 134)MIS results in less improvement, but saves 239 € per 1% Quality of life (EuroQol; QALY) Score over 1 year follow-up819 € (n = 102)0.833 (n = 102)1030 € (n = 111)0.837 (n = 111)MIS results in less improvement, but saves 47,348 € per QALY MIS Minimal intervention strategy, UC Usual care, ICER Incremental cost-effectiveness ratio, n Number, QALY Quality adjusted life yearaDifference in clinical outcomes between baseline and 12 months follow-upFig. 1Cost-effectiveness plane for functional disability (RDQ) in which MIS is compared to UC
Sensitivity analyses
Imputation of missing cost data led to a mean difference of −628 € (95% CI −1123 to −81 €) in total costs. Imputation of missing data on days of absenteeism led to a mean difference of −545 € (95% CI −1031 to −40 €) in total costs. Both differences are statistically significant and in favor of MIS.
Discussion
The results of our primary analysis showed no statistically significant differences in total costs or clinical outcomes between our psychosocial intervention and UC in patients with (sub)acute LBP in general practice. However, the results of our sensitivity analyses are inconsistent with those of the primary analysis. In this discussion section we will focus on the interpretation of our cost data and the methodological issues involved when interpreting cost data. In previous papers we have discussed several methodological issues involved when interpreting the clinical outcomes (e.g. the quality of the training sessions and interventions) [20, 21].
Comparison to the literature
A recent review on the cost-effectiveness of treatments for patients with LBP reported that 6 of the 17 studies concluded that the intervention of interest was more cost-effective than the control intervention [43]. Unfortunately, no definite conclusions for the cost-effectiveness of a specific intervention could be given as the number of economic evaluations per type of intervention was limited. More recently the cost-effectiveness analyses of two trials on psychosocial primary care interventions for LBP have been published. The UK BEAM Trial compared spinal manipulation, exercise classes incorporating cognitive behavioral principles, spinal manipulation plus exercise classes, and best care [40, 41]. Although the authors conclude that spinal manipulation is a cost-effective addition to “best care”, as it generates 0.04 more QALYs for an extra 279 € [37], others question this conclusion [6, 39]. Another study in primary care compared advice directed towards promoting self-management and modifying beliefs and behavior, and routine physiotherapy treatment with advice only [14, 34]. The authors conclude that advice should be considered as the first-line treatment, as out-of-pocket expenses of patients receiving routine physiotherapy were significantly higher (41£, 59 €), while differences in either QALYs (0.02) or National Health Service costs (20£, 29 €) were not significantly different [34]. Both the above mentioned studies found lower QALYs and higher health care costs over 12 months than we found in our study. The shorter duration of the LBP episode at baseline of our patients and, thus, their more favorable prognosis may (partly) explain these results. In contrast to our study, both the trials did not include indirect costs in their cost-effectiveness analyses, even though it is generally agreed upon that indirect costs associated with work absence due to LBP account for high economic costs in western societies [28, 45].
Methodological issues and secondary analyses
In our study, we used the British sample as reference population for the utilities as, until recently, these were the only reference data available in the Netherlands. Recently, a EuroQol transformation has been introduced based on a Dutch sample [24]. We decided not to use this Dutch transformation as (1) it has only been internally validated through bootstrapping methods but not yet externally validated; (2) the representativeness of the, rather small (n = 298), Dutch sample can be debated [4] and, finally (3) use of the Dutch transformation would complicate comparison across international studies. A comparison between the use of a Dutch or UK sample showed that, although QALYs based on the Dutch sample were slightly higher compared to the British sample, the mean differences between the groups, in this case two primary care interventions for treatment of depression, were largely the same [2].
We based our sample size calculations on demonstrating a clinically relevant difference of 2.5 points on the RDQ instead of demonstrating the cost-effectiveness [20]. Although the usefulness of sample size calculations in economic evaluations has been debated [1], the required sample size in an appropriately powered cost-effectiveness study is expected to be much larger than in a clinical effectiveness trial [3].
Work absence due to LBP was the main contributor to the total costs associated with LBP. The number of days of absenteeism was twice as high in the UC group as in the MIS group. Although not statistically significant, this finding induced us to explore whether MIS was cost-effective among patients having a paid job (n = 93 MIS; n = 110 UC). This post-hoc subgroup analysis showed that the difference in total costs amounted to −548 € (95% CI −1137 to 200 €) in favor of MIS, which was not statistically significant. As this subgroup analysis was clearly insufficiently powered, and as other early interventions have been shown to reduce sick-leave in workers [17, 19, 22] one may hypothesize that MIS may be cost-effective in an occupational setting. The sensitivity analyses with imputed data were less underpowered and, interestingly, showed statistically significant differences in total costs between groups. The question now arises which analysis we should value most.
Interpretation of the conflicting results
A complete case analysis has the advantage over an imputed analysis that no assumptions have to be made regarding imputation of data that are characterized by large variation and irregular distributions. However, a complete case analysis does not include all participating patients, which reduces the statistical power and which may introduce bias. Advocates of the (conclusions of our) complete case analysis may, among others, be (1) researchers who do not favor imputation techniques when data are available for 80% of the cases; (2) GPs, as application of MIS will increase their workload, with no evidence of improvement of the patients’ functional disability, recovery rates, or pain intensity. Advocates of the (conclusions of our) sensitivity analysis may among others be (1) researchers who favor imputation techniques; (2) policy makers, who are interested in all relevant costs and effects regardless of who will pay the costs and who may benefit; or (3) managers in workplace settings as they may be especially interested in the reduction of costs due to sick-leave.
The cost-effectiveness planes do not provide a solution for the impasse. The plane for functional disability showed that 96% of the bootstrapped cost-effect pairs, although very close to the origin of the plane, were located in the southern quadrants. Does this indicate cost-effectiveness of MIS? The answer to this question will depend on the way one defines cost-effectiveness. Obviously, when a new intervention is clinically more effective and less costly than the old intervention (south–east quadrant), there will be no debate about cost-effectiveness and implementation of the new intervention. When a new intervention is clinically more effective and more costly (north-east quadrant), a new intervention will be considered cost-effective when costs stay below a certain threshold. Dowie (2004) [8], however, questions why an intervention should not also be implemented when it is less effective but does save substantial costs, pleading for defining a threshold that extends into the south-west quadrant. This threshold can be a straight line from the north-east to the south-west quadrant, or kinked at the origin of the cost-effectiveness plane, indicating that the selling price for an unit of effect is greater than the buying price of an additional unit of effect [29].
Although there are various points of view, we conclude that (Dutch) GPs should not replace their UC by MIS in patients with (sub)acute LBP. This conclusion is based on the results of the complete case analysis, because this was our pre-planned analysis. The second reason is that the difference in costs, if any, was mainly caused by a small proportion of the population who reported sick leave due to back pain. We cannot rule out the possibility that this was a chance finding. The third reason is that MIS is a new approach in general practice. Implementation of MIS will meet many difficulties, given the lack of evidence for clinical effects, the need for training of GPs and the increase of GP workload. The final, and maybe most important reason is that our study is the first and, as far as we know, the only study that investigated the cost-effectiveness of a psychosocial intervention in patients with (sub)acute LBP in general practice.
Conclusions
Results of only one study are insufficient to establish firm evidence on the cost-effectiveness of an intervention. More studies on the cost-effectiveness of psychosocial interventions in general practice are needed, thereby taking into account some of the factors that may explain why our intervention was not more successful than usual GP care as described in previous papers [20, 21]. As yet, we conclude that (Dutch) general practitioners should not replace their usual care by our new intervention.

low back pain
general practice
cost-effectiveness
psychosocial factors
minimal intervention strategy


PubMatrix: a tool for multiplex literature mining

Background Molecular experiments using multiplex strategies such as cDNA microarrays or proteomic approaches generate large datasets requiring biological interpretation. Text based data mining tools have recently been developed to query large biological datasets of this type of data. PubMatrix is a web-based tool that allows simple text based mining of the NCBI literature search service PubMed using any two lists of keywords terms, resulting in a frequency matrix of term co-occurrence.
Background
With the advent of high throughput genomic and proteomic approaches, the ability to generate data has outstripped the ability to assign biological relevance. Searching the MEDLINE literature database of greater than 14 million entries one-by-one makes establishing biological significance a daunting task. The basic PubMed search window contains a typical single search box for the input of simple keyword combinations. PubMed does allows complex searches using advanced search options, but this requires some knowledge of string search assembly, and an understanding of the PubMed Entrez programming utilities. These are still relatively obscure for many molecular biologists.
Literature mining approaches have been developed to place multiplex biological datasets into context relative to published medical literature. Computational tools such as PubGene [1], VxInsight [2], MedMiner [3], EASE [4], MeshMap[5], XPLORMED [11], AbXtract [12], and HAPI [13] are available which allow the user to query more complex gene name or keyword combinations, including multiplex proteomic or cDNA microarray results, versus literature citations in PubMed with defined types of output. These computational tools use different strategies in literature mining and in some cases produce statistical significance or graphical displays.
Similarly, literature based annotation projects such as the GO project [9] have devised a complex hierarchical annotation system using expert annotators based on a defined controlled vocabulary. This is important due to significant problems with nomenclature in molecular biology. Although quite useful, the GO approach does not allow for flexibility, variable interpretation, or individual investigator input in the hierarchies assigned to individual genes. In this report, we describe a simple, freely accessible, web based application for basic literature mining of PubMed that performs automatic multiplex Boolean queries. This allows the naive user to assign biological relevance and annotate gene lists through PubMed.
Implementation
PubMatrix is a CGI front-end application, which submits queries consisting of search and modifier terms against NCBI's PubMed database and presents the results as a matrix of document hits. Results are stored in a database for retrieval and are presented as hyperlinks to the user for rerunning individual queries of interest. The application runs on an Apache http server using the PERL programming language and a MySQL database for storing terms and results.
Results
PubMatrix is a simple intuitive multiplex comparison tool requiring no user understanding of algorithm design, perl, or scripting, and minimal instruction time. It allows automatic systematic searching of PubMed followed by a quick intuitive survey of results, and as such, dramatically reduces the investigator time needed to query PubMed as compared to a gene-by-gene approach. Moreover, it is systematic and objective. Unlike typical PubMed searches performed on an ad hoc basis, the 1st and the 1000th query are searched in an unbiased manner. This helps avoid becoming distracted with seemingly interesting comparisons early on in a traditional literature search session. It is flexible in the sense that any list of terms in almost any combination may be used. With PubMatrix, large lists of keywords can be compared and, when used with lists of gene names and function, may be used to analyze and annotate microarray gene lists and datasets. GO keywords may be used to annotate gene lists in a semi-automated fashion. Additionally, the ability to save searches in an archive allows sharing among collaborators and public accessibility of curated lists of useful search results and search terms.
Figure 1 shows the web interface for PubMatrix. Data entry begins with creating two lists of keyword terms, (figure 1) SEARCH TERMS and MODIFIER TERMS. These can be any simple words or strings of words. Typically official gene symbols (TP53, CTLA4, etc.) can be used for microarray or proteomic data. These lists can be pasted into the appropriate data entry boxes on the page or loaded as a text file through the browser. Essentially any search combination that can be loaded into the basic PubMed search window can be run in PubMatrix in matrix file format. This gives a broad search capability as compared to PubGene [1], which is limited to gene identifiers only. Terms in either list can contain PubMed field limits (i.e. author, title, abstract, journal, publication date, etc.) subject to PubMed/Entrez formatting specifications [10]. Compound terms in either list can be used as well. Like PubMed, success in using PubMatrix is dependent upon the quality of the input terms. If terms are general, you may end up with general results, if they are too specific, you may limit the search inappropriately. As in PubMed, PubMatrix makes no provision for nomenclature curation and provides no measure of statistical significance. General terms may be appropriate for some searches while specific terms may be useful for others. If the terms used are inappropriate or non-specific, the search will return inappropriate and low quality results; quisquiliarum ineo quisquiliarum egredior.
Figure 1
The PubMatrix Data Input Page
There is currently a 100 SEARCH TERM and 10 MODIFIER TERM limit on the search capability due to NLM automatic script searching restrictions. The size and speed of PubMatrix is largely determined by NLM restrictions. In unrestricted tests, PubMatrix rapidly returned results using term lists of over 10,000 terms. The size limit of 100 × 10 will generally accommodate a gene list from a published summary table of microarray results or genes from a cluster produced from a typical clustering program. After data entry, the PubMatrix program then performs pairwise comparisons of each SEARCH term against each MODIFIER term using the Boolean operator "AND", capturing only the pairwise frequency counts found in PubMed. It does not capture the actual PubMed record. Relative frequencies are then presented in an html matrix table (Fig 2) of control terms versus search terms. This table can then be surveyed or sorted for positive hits. Clicking on a single frequency number in the matrix table then performs a de-novo individual query for that single pairwise combination in PubMed. In this way the user can drill down or focus on specific interesting combinations.
Figure 2
The report page from a simple search of gene names versus neural modifier terms. All reported numbers are hyperlinked and will initiate a de-novo search for that specific term combination.
Productive searches using broadly useful control term lists have been assembled into an associated PubMatrix public archive. These previously used search term lists may be commonly useful and may aid other investigators in subsequent searches. Examples include, official gene symbols, functional descriptors, cytogenetic bands, or polymorphic markers. Likewise, non-molecular term lists have been used and archived which may be broadly useful, such as commonly prescribed drugs, common diseases, and meeting speakers, among others. For example, prior to a meeting, an attendee can rapidly search all the meeting speakers names against important keywords found in the meeting program to provide a one-page summary of speakers scientific interests. Archived term lists can be copied to initiate new searches with new modifier term combinations. Table 1 gives examples of categorical lists of terms used in PubMatrix. Searches using these term lists can be found in the PubMatrix: Public Results page.
Table 1
Examples of categorical search lists
Category
Examples
Official Gene Symbols
APOB, ACE, BDNF, CD45, ...
Polymorphic markers
D1S478, D6S470, D13S193, ...
DNA sites
AAATTT, CAGCAG, TTTTTT, ...
Chromosomal bands
1ter*, 1p36*, 1p35*....Xq27*, Xter*
Countries
sweden, canad*, mexic*, finland, ...
Common Prescription drugs
acetaminophen, acyclovir, albuterol, alprazolam, ...
Common diseases
atopic dermatitis, asthma, crohn's, Celiac, Graves',...
Date of Publication
1973 [dp], 1974 [dp]......2000 [dp], 2001 [dp], 2002 [dp]
Meeting Speakers
Weiss A, Pierce SK, Kupfer A,...
PubMatrix tables can be combined or processed further to provide visual displays or summaries of complete experiments or large datasets in the context of medical literature. Figure 3 shows a display of cDNA microarray results of an ovarian cancer cell line treated with the drug cisplatin. The literature results are displayed in the context of gene expression ratios (Z-ratios). Similarly, Figure 4 shows a comprehensive term list of human cytogeneic bands covering the human genome (1p36*, 1p35*, 1p34*...Xter*) versus the single term "Autoimmune". When displayed by chromosome, major autoimmune loci are identified. These include the major histocompatibility complex, chromosome 2q (CTLA4), as well as APECED on 21q. Figures 3 and 4 were displayed in MS EXCEL using the 3-D chart view option. Moreover, PubMatrix tables can be pasted into spreadsheet programs and imported into other types of data visualization programs such as CLUSTER/TREEVIEW [11] or SPOTFIRE [12] for graphic display and manipulation.
Figure 3
Gene expression results (Z-ratio) of cisplatin treatment of an ovarian tumor cell line versus keywords relevant to cisplatin resistance. This graph was constructed in MS EXCEL directly from a PubMatrix search result table using the 3D chart view option after adding gene expression values (Z-ratios).
Figure 4
Visual display of chromosomal-band term list versus the term. "autoimmune". Search terms were 313 sequential human chromosomal bands (1pter, 1p36, 1p35, 1p34, etc....Xq26, Xq27, Xq28, Xqter) versus the single modifier term "autoimmune". This graph was constructed in MS EXCEL using 3D chart view option after separating individual chromosome results into individual columns.
Conclusions
PubMatrix allows a simple systematic approach to query the medical literature in PubMed with comparative keyword lists. It performs simple automatic queries and greatly reduces analysis time. In this way, increasingly large datasets generated by high-throughput multiplex assays such as proteomic or microarray assays can be mined, archived, displayed, and annotated for biological and disease relevance.
Availability and requirements
PubMatrix is available for free use at this URL:
Authors' contributions
KGB and TJB conceived the approach and participated in early design and testing. DAH, GD, RAL, and CC participated in software design and testing. JE participated in web design, database development, and algorithm modification. All authors read and approved the final manuscript

pubmed
literature mining
microarray
proteomic


Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily.
Introduction
Spina bifida and anencephaly – the most common neural tube defects (NTDs) – are serious birth defects that occur early in pregnancy, often before a woman realizes she is pregnant. Important studies show that intake of the B vitamin folic acid reduces the incidence of NTDs by 50–70% when taken before conception and during the first trimester of pregnancy [1, 2]. This compelling research prompted the 1992 U.S. Public Health Service (USPHS) recommendation that all women of childbearing age who are capable of becoming pregnant consume 400 micrograms (mcg) of folic acid daily [3]. For women who previously had an infant with an NTD and were planning a pregnancy, it was recommended that they consume a much larger dose, 4,000 mcg of folic acid per day at least one month before becoming pregnant and during the first three months of pregnancy [3].
In 1998, the 1992 USPHS recommendation was reaffirmed by the Institute of Medicine, which stated that women capable of becoming pregnant should take 400 micrograms of “synthetic folic acid” daily from fortified foods or supplements or a combination of the two, in addition to consuming natural folate from a varied diet [4]. Additionally, in 1998 the Food and Drug Administration (FDA) began requiring folic acid fortification of enriched breads, cereals, flours, pastas, rice, and other grain products [5], to aid in increasing folic acid consumption by an estimated average of 100 mcg daily in women of childbearing age. Other organizations, such as the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, have supported the USPHS recommendation [6, 7]. National and state organizations implemented educational and media campaigns during the mid-1990s to promote the awareness and consumption of folic acid among women of childbearing age [8, 9]. Since the implementation of national policies, the number of pregnancies affected by NTDs in the U.S has decreased approximately 26% – from 4,000 affected pregnancies prior to fortification to 3,000 affected pregnancies after fortification [10]. Despite these efforts, the 50 percent reduction anticipated by the USPHS in 1992 has not been forthcoming. This report summarizes results from nine surveys conducted between 1995–2005 after the USPHS 1992 recommendation and folic acid fortification. It documents the steady increase in awareness and knowledge of folic acid – and the as yet modest change in consumption of a vitamin containing folic acid – among U.S. women of childbearing age.[11].Table 1Awareness, knowledge, behavior, and source of knowledge regarding folic acid among women of childbearing age – United States, 1995–2005bCharacteristic199519971998200020012002200320042005Awareness Heard or read about folic acid526668757980797784Knowledgea Knew folic acid can help prevent birth defects41013141920212419 Knew folic acid should be taken before pregnancy2671071010127Behavior Take folic acid daily (all women)283232342933324033 Take folic acid daily (non-pregnant women)253029322731303731Source of knowledgea Health-care provider131519202225302926 Magazine/Newspaper353631302727252826 Radio/Television102223242525211918Good sources of folic acida Green leafy vegetables–––242327282526 Fortified cereals–––244335Source: March of Dimes Birth Defects Foundation. From 1995–2004 the margin of error for estimates is ±3%. In 2005, the margin of error for estimates was ±2%.Note:−=Not available.aOf women who report being aware of folic acidbStatistical estimates were weighted to reflect the total population of women aged 18–45 years in the contiguous United States who resided in households with telephones
Methods
The data for this study include a national sample of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005. The March of Dimes Birth Defects Foundation contracted the Gallup Organization to conduct random-digit-dialed telephone surveys. Since 1995, response rates have ranged from 24% to 52%. The response rate for the 2005 survey was 32% (2,647 women). Statistical estimates were weighted based on Current Population Survey (CPS) data to reflect the total population of women aged 18–45 years in the contiguous United States who resided in households with telephones. In 2005, the sampling design included an oversampling of women ages 18–25. In 1995–2004, the margin of error for estimates based on the total sample size was ±3% and in 2005 it was ±2% . The questionnaire and methods used were described previously and were the same in all survey years [12].
Results
Table 1 displays the percentage of women reporting awareness of and knowledge about folic acid, and their daily use of vitamins containing folic acid. Between 1995 and 2001, the percentage of women reporting having heard or read about folic acid increased from 52% in 1995 to 79% in 2001. Since 2001, awareness of folic acid has remained relatively constant at about 80%. Of all women surveyed in 2005, 19% knew that folic acid prevented birth defects, compared to 4% in 1995. Also in 2005, 7% of women knew that folic acid should be taken before pregnancy, compared to 2% in 1995. The proportion of all surveyed women who reported taking a vitamin supplement containing folic acid daily has remained almost unchanged but increased gradually from 28% in 1995 to 40% in 2004, but decreased to 33% in 2005. Of women surveyed in 2005 who were aware of folic acid, 26% identified green leafy vegetables as good sources of folic acid. However, in 2000, fortified cereals were added to the list of possible sources, and only 2–5% of women identified fortified cereals as a good source of folic acid.
Table 1 also displays women's reported sources of information about folic acid. From 1995 to 2005, the proportion of women who reported learning about folic acid from health care providers showed a two-fold increase from 13% in 1995 to 26% in 2005. Of women surveyed in 2005, 31% reported that their health care provider discussed the benefits of folic acid with them, compared to 24% in 2001. Of the same group of women in 2005, 30% reported being told by their health care provider that folic acid prevented birth defects. However, only 7% of women in 2005 reported that their health care provider said folic acid needs to be taken before pregnancy. This statistic has ranged from 3% in 2004 to 8% in 2003 since its inclusion in the survey in 2002.Table 2Percentage of women of childbearing age 18–45 who reported awareness of folic acid by selected sociodemographic characteristics – United States, 2000–2005aCharacteristic200020012002200320042005Race/ethnicity White788282838187 Non-White626971686871 Hispanic626969727173 Non-Hispanic768081807984Age group (yrs) 18–24687370737072 25–34768284828088 35–45778081818087Education Less than high school546059565658 High school/Trade/Technical/ Vocational Training667273767078 College (any)838687868690Annual household income < $25,000617168696672 $25,000–$39,999767776797984 $40,000–$49,999807784878287 >=$50,000848888868790Source: March of Dimes Birth Defects Foundation. From 1995–2004 the margin of error for estimates is ±3%. In 2005, the margin of error for estimates was ±2%.aStatistical estimates were weighted to reflect the total population of women aged 18–45 years in the contiguous United States who resided in households with telephones.
For the last ten years, the percentage of women learning about folic acid from media sources such as radio and television increased from 10% in 1995 to 18% in 2005, whereas information about folic acid obtained from magazines or newspapers decreased from 35% in 1995 to 26% in 2005. These results are shown in Table 1.
Table 2 displays the percentage of women of childbearing age 18–45 who reported awareness of folic acid by selected sociodemographic characteristics. In 2005 the women least likely to be aware of folic acid were non-white women (71%), women aged 18–24 years (72%), those women with less than a high school education (58%), and those with a household income of less than $25,000 (72%). These results are consistent with years prior to 2005.
Table 3 displays the percentage of women of childbearing age 18–45 who reported taking folic acid daily, by selected sociodemographic characteristics. Of all women surveyed in 2005, those least likely to consume a vitamin containing folic acid daily include non-white women (23%), those women aged 18–24 (24%), those with less than a high school education (20%), and those with household incomes of $25,000 or less (27%). Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Among women who were surveyed in 2005 who were currently pregnant, 90% reported taking a vitamin containing folic acid daily compared to 79% in 1997.Table 3Percentage of women of childbearing age 18–45 who reported taking folic acid daily, by selected sociodemographic characteristics – United States, 1995–2005aCharacteristic199519971998200020012002200320042005Race/ethnicity White––33363036344336 Non-White––26262325283123 Hispanic––29362326293827 Non-Hispanic––32342934334034Age group (yrs) 18–24212323292222253124 25–34303634343237343936 35–45303534363036354637Education Less than high school222020182621211920 High school/Trade/Technical /Vocational Training263027312429283231 College (any)303736383238374836Annual household income < $25,000202228262223243027 $25,000–$39,999313229342634314028 $40,000–$49,999323431372833394837 >=$50,000334338403540384638Pregnancy status Currently pregnant–7979848074828190 Not currently pregnant253029322731303731Source: March of Dimes Birth Defects Foundation. From 1995–2004 the margin of error for estimates is ±3%. In 2005, the margin of error for estimates was ±2%.Note: -=Not availableaStatistical estimates were weighted to reflect the total population of women aged 18–45 years in the contiguous United States who resided in households with telephones
In 2005, 67% of childbearing age women reported they did not take daily supplements. The most common reasons for not taking any daily vitamin or mineral supplements are that they “forget to take them”, stated by 28% of women, or “don't feel they need them” as reported by 16% of women. However, in 2005, 86% of women who were not currently taking daily vitamins or mineral supplements reported they would be likely to start taking a multivitamin daily if advised by their health care provider or physician.
Discussion
The findings in this study show that whereas a large percentage of women have heard of folic acid, only a small proportion are aware that folic acid prevents birth defects and should be taken before pregnancy. Furthermore, despite the USPHS recommendation in 1992 [3] the percentage of women taking a vitamin supplement containing folic acid daily has only modestly increased between 1995 and 2005. There was a substantive increase in the percentage of women taking folic acid daily in 2004, but this increase was not sustained in 2005. Clearly, the observed increases in awareness and knowledge about folic acid are not translating into increased multivitamin use.
Increased awareness of the importance of folic acid is due in part to educational outreach activities undertaken over the years by CDC, the March of Dimes Birth Defects Foundation and its chapters, the Spina Bifida Association of America, and members of the National Council on Folic Acid. These activities culminated in a national meeting in January 1999 to coordinate a folic acid promotional campaign (May through September 1999) with continuing independent educational outreach efforts [8]. Although there were no substantial changes in folic acid use, recent dietary habits might provide insight into the sudden increase in folic acid use in 2004. A recent study found that women on low-carbohydrate diets were 50% more likely to take folic acid daily than women on other diets; however, in 2005, folic acid use was similar across dieting types [13]. The results from the 2004 survey may be an anomalous finding, given that many of the findings returned to pre-2004 levels (e.g., multivitamin use). Our findings may suggest the need for more continued and increased media messages to encourage women to consume adequate amounts of folic acid every day through fortified foods, dietary supplements, and a folate-rich diet. Furthermore, communities should identify food products that provide recommended levels of folic acid available in local grocery stores, and encourage women to select diets with sufficient folic acid.
Recent educational efforts alone do not appear to be adequate to demonstrate an impact on changing behavior with regard to folic acid consumption. The findings from this report can be used to develop multi-pronged targeted public health programs to increase the number of women of childbearing age consuming a vitamin containing folic acid daily. Demographic, sociocultural, and environmental factors impact behavior and more attention must be given to these factors. Results from these surveys indicate that variations exist in folic acid awareness, knowledge, and use among women of different race/ethnicity, age groups, education levels, and socioeconomic status. This suggests that the linkage between folic acid awareness, knowledge, and use is more complicated than simply increasing awareness and knowledge. Non-white women, those between the ages of 18–24, those less educated, and those of a lower socioeconomic status are associated with both lower folic acid knowledge and lower use of a vitamin containing folic acid. Targeted messages and teachable opportunities of communication for younger women, women of racial and ethnic groups, and women of low socioeconomic status need to be identified and mobilized to increase the number of childbearing age women taking folic acid daily, regardless of pregnancy plans.
Our results indicated that despite the fact that some women learn about folic acid from their health care provider, most women are not currently following their health care provider's advice even though they might feel the recommendation is important. This is apparent when looking at the proportion of women taking a multivitamin daily. In addition, women report they do not take a vitamin containing folic acid because they “feel they don't need to”, or are not receiving the folic acid message from their health provider. More research is needed to understand what the motivators and barriers are for consuming a multivitamin containing folic acid daily to design appropriate interventions (whether service delivery, policy, media messages, or educational in nature) for women of childbearing age. It is important to continue to target educational efforts at health care providers with emphasis on the importance of women of childbearing age taking folic acid daily to prevent NTDs. But, education of health care providers may not be enough by itself. Changing health care provider practices is not merely a matter of knowledge acquisition. Public health programs need to forge stronger alliances with the health care delivery systems at the local and national level to develop and incorporate meaningful folic acid messages into routine counseling and existing health programs and services, since preconceptional counseling is not available to all women of childbearing age. Strategies are needed to understand the context of patient and provider interaction to promote consumption of a daily vitamin containing folic acid among all women of childbearing age, regardless of whether or not they are planning a pregnancy.
The findings from this survey are subject to several important limitations. First, because women under the age of 18 were not included in the survey, the full extent of folic acid knowledge and consumption among the entire population of women of childbearing age is unknown. Second, women without telephones were excluded; therefore, data may underestimate the number of women of childbearing age from low socioeconomic groups. Third, folic acid knowledge and consumption of nonparticipants might have been different from those of participants: participating women were more highly educated than the total U.S. population. The prevalence of consuming vitamin supplements might have been higher among these women than among U.S. women in general because vitamin consumption is positively correlated with education [11, 12]. Fourthly, folic acid use may have been under ascertained since we did not have information on women's dietary folate consumption or their folate levels. Further, self-report of dietary intake, such as taking multivitamins, could be biased by social desirability – the tendency of respondents to respond in a way so as to avoid disapproval, rather than reporting actual beliefs or actions. Finally, surveys of a more representative sample of women of childbearing age in the United States are needed to obtain more precise estimates of folic acid use among this population.
Policy and practice implications
Fortification efforts are an effective method of reducing the number of NTD-affected pregnancies, and have led to a 26% decline in the number of NTD-affected pregnancies since the 1998 mandate that enriched cereal grain flours be fortified with 140 mcg per 100 gram (g) [10]. Although this is a substantial decline, it does not reach the 50% reduction estimated by the USPHS in 1992 [1]. While the U.S. is seeing a decline in the number of NTDs, other countries have seen similar or greater declines. In Chile for example, wheat flour was fortified in 2000 with 220 mcg folic acid per gram of the pre-mix already used in wheat flour. Nine public hospitals in Santiago, Chile, which account for approximately 25% of the births in that country, reported a 40% decline in the number of NTDs [14]. Canada's flour was fortified with folic acid in 1998 with 150 mcg of folic acid per 100 g of grain and certain provinces reported almost a 50% decline of NTDs[15].
Some countries have chosen to recommend the use of folic acid supplementation for women of childbearing age instead of fortification. One study examined data from thirteen birth defect registries from areas in Europe and Israel with over 8,000 cases of spina bifida and anencephaly to determine the impact of recommendations on the rate of NTDs [16]. Although some countries saw a slight decline in rates, the majority of countries saw no detectable decrease in the rates of NTDs using recommendations for supplementation alone [16]. This small decline implies that although recommendations might be an important aspect of reducing the rate of NTDs, programs such as fortification could have a broader and more effective impact on the overall rates of NTDs. Countries who try to use a combination of methods – such as fortification and supplementation, along with recommendations and education programs – might see a greater decline in the rates of NTDs.
Conclusions
The Healthy People 2010 objectives call for an increase to 80% in the number of nonpregnant women aged 15–44 years consuming daily amounts of 400 mcg of folic acid through fortified foods or dietary supplements (Objective 16–16a) and to increase the median red blood cell (RBC) folate level to 220 ng/ml among nonpregnant women aged 15 to 44 years by 2010 (Objective 16–16b) [17]. Although substantial increases in RBC folate levels among women of childbearing age has been achieved [18], more aggressive efforts are needed to increase the number of women consuming 400 mcg of folic acid daily through fortified food or dietary supplement to reduce the prevalence of NTDs.
To succeed in eliminating all folic acid preventable birth defects beyond what fortification has already achieved, more must be done besides educating women and their health care providers. Pregnancies and births affected by spina bifida or anencephaly have profound physical, emotional, and financial effects on families and communities. This year there will be an estimated 3,000 NTD-affected pregnancies. This study reinforces the need for public health practitioners to mobilize multiple sectors, including health care professionals, government organizations, state and local organizations, advocacy groups, and concerned citizens to coordinate efforts and activities to help alleviate a devastating public health issue.

folic acid consumption
childbearing age women
multivitamin use