Academic Medical CenterUniversity of Amsterdam, Department of General Practice/Family Medicine, Amsterdam, The Netherlands
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Abstract |
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Key words: anxiety/grief/quality of life/randomized controlled trial/spontaneous abortion
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Introduction |
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Equivalence in terms of complication rate, robust as these findings may be, does not rule out differences in health-related quality of life (HRQL) in women undergoing either expectant management or surgical evacuation. If substantial, these differences may even play a dominant role in guidelines and individual decisions.
In a randomized controlled trial we measured general and specific quality of life in women with miscarriages, who were managed either expectantly or by surgical evacuation. Assuming that quality of life might well be influenced by patients' treatment preferences, these results were compared with those of women who, because of a treatment preference, were managed according to their own choice (Henshaw et al., 1993).
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Materials and methods |
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Transvaginal ultrasonographic criteria for early fetal demise were: a mean gestational sac diameter >15 mm without a measurable embryonic pole, an embryo without cardiac activity, or a gestational sac diameter <15 mm, not showing any growth after a 7 day interval (Coulam et al., 1997; Deaton et al., 1997
). An incomplete miscarriage was diagnosed in cases of ultrasonographical evidence of retained products of conception >15 mm in the anteroposterior (AP) diameter. All transvaginal scans were performed by trained physicians using a transvaginal 6.5 MHz sonographic probe (Hitachi Corporation, Tokyo, Japan).
Assignment
After written informed consent had been obtained, women were randomized by the attending physician to either expectant (n = 64) or surgical (n = 58) management, using central electronic randomization. Women who refused randomization because of a preference for either one of the management options received the treatment of their own choice (preference groups, n = 126 expectant versus n = 179 surgical).
Interventions and follow-up
Surgical uterine evacuation was performed within a week after inclusion under local or general anaesthesia in daytime surgery according to the women's preference and setting availability.
Both randomized and preference groups were assessed clinically and by ultrasonography during the bi-weekly appointments at the outpatient clinic until a complete evacuation of the uterus was established either by surgical evacuation or through spontaneous loss. Women who became impatient while being managed expectantly and requested surgical evacuation were scheduled to undergo curettage within a week, but were analysed in the original treatment group on an intention-to-treat basis.
Questionnaires were filled out at five time points: immediately after inclusion, and 2, 4, 6 and 12 weeks later. All questionnaires comprised the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36), the State-trait Anxiety Inventory (STAI) and the Perinatal Grief Scale (PGS). The first questionnaires also comprised sociodemographic questions.
The questionnaires were completed by the patient at home and were returned in a pre-stamped envelope. Reminders were sent to non-responders once after each time point.
Outcome measures
We used three measures, all validated in Dutch, to analyse differences in HRQL between patients: the generic SF-36, the domain-specific STAI, and a short form of the disease-specific PGS (van der Ploeg et al., 1981; Toedter et al., 1988
; Potvin et al., 1989
; Ware and Sherbourne, 1992
; Aaronson et al., 1998
). We used the `acute' version of the SF-36, employing a 1 week time frame. The SF-36 covers eight sub-scales of health status: physical functioning, mental health, role limitations because of emotional problems, role limitations because of physical problems, social functioning, bodily pain, vitality and general health perceptions. The scores of the eight sub-scales, which range from zero (worst health) to 100 (best health), were conventionally aggregated into the standardized Physical Component Summary scale (PCS) and Mental Component Summary scale (MCS), both with mean 50, SD 10. The STAI contains two 20-item scales covering both current (state) and background (trait) anxiety; items are rated on a four-point scale with total scores ranging from 2080, where higher scores represent higher levels of anxiety (Spielberger et al., 1970
; van der Ploeg et al., 1981
). The PGS measures grief associated with pregnancy loss. The short form used here contains 33 questions, to be answered on a five-point Likert scale ranging from `strongly agree' to `strongly disagree' with a neutral mid-point. The PGS consists of three sub-scales: active grief, difficulty coping and despair, which range from 1155 with higher scores indicating more grief. Active grief is the normal grief reaction that may follow a pregnancy loss. Difficulty coping and despair represent increasingly severe forms of grieving. The PGS had previously been confirmed as reliable and valid in the evaluation of women who miscarried (Potvin et al., 1989
; Cuisinier et al., 2000
).
Reference scores for the SF-36 sub-scales were obtained from published data of a Dutch population sample (1640 years of age) (Ware et al., 1993, 1994
, 1998
; Aaronson et al., 1998
).
Sample size
For the power calculation we focused on the SF-36. Assuming a five-point difference in the summary PCS or MCS measures as being clinically relevant, we needed 33 patients in each randomized group to detect this difference (alpha = 0.05, beta = 0.2) (Ware et al., 1994).
Statistical analysis
We analysed the data according to the intention-to-treat principle, i.e. women were analysed in the group into which they were randomized, irrespective of whether or not they received that treatment. Women with missing data were included if at least two sets of questionnaires were available. We assumed that women with a short period until complete evacuation of the uterus (spontaneously or by surgical intervention) might be under-represented in the study and we therefore compared the time until complete evacuation between included and excluded women. Differences in patient characteristics and HRQL at inclusion between the randomized groups and the preference groups were analysed using descriptive statistics. We also analysed the relation between period of delay in conceiving (in months) and the mental health score after 12 weeks.
We employed repeated measurements design to compare the HRQL changes of the randomized groups and the preference groups in more detail. A mixed linear model was used to sort out the treatment effect and the treatment assignment effect, apart from time and other effects, as expressed in observed patterns in the various quality of life measurements. The mixed linear model methodology accounts for the correlation between different measurements over time within the same women, thus avoiding overestimation of specific effects such as due to treatment. For each participant we assumed in this analysis that the more measurements were closer in time, the more they were correlated. Our model included the following explanatory variables: the (initial) treatment option (at four different levels: curettage and expectant in both the randomized and preference group), time (as a categorical variable with four levels, excluding the baseline measurements), interaction between treatment and time, and the baseline measurement. P values < 0.05 were considered significant. Results were presented as differences in mean score with 95% confidence intervals (Verbeke and Molenberghs, 1997; Littell et al., 2000
).
The Statistical Package of the Social Sciences (SPSS, version 10.07) was used for all standard analyses. All mixed models were done in SAS 6.12 (syntax and data available from the authors).
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Results |
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Analysis
No significant differences in sociodemographic or clinical characteristics were present between the randomized groups, nor between the preference groups. Also, no differences in prior experience with one of the management options, education, native country or anxiety (STAI) were observed.
At study inclusion we did not find significant differences in scores between the two randomized groups (data not shown). However, women preferring expectant management showed significantly better scores on the mental health sub-scale (mean score 66) than women preferring curettage (mean score 57). Similarly, at inclusion women preferring expectant management showed significantly less active grief (mean score 30) than women preferring curettage (mean score 35).
The course of the (unadjusted) mean values for the SF-36 mental and physical summary scores, STAI and PGS total scores in the four groups are illustrated in Figure 2.
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Changes in HRQL over time in the four groups were analysed in a repeated measurements mixed model.
Randomized groups
There were no significant differences between the two treatments in physical health (PCS) scores (treatment effect P = 0.7). Women randomized to expectant management, however, had significantly better mental health (MCS) scores (treatment effect P = 0.004). The overall differential treatment effect (difference between the expectant management group versus the curettage group, all time points together) was 7.4 points on the MCS in favour of expectant management. The difference at 12 weeks was still 6.3. There were no significant differences in changes over time between the two treatment arms in PCS and MCS (time by treatment P = 0.6).
We found no significant differences in improvement between the two arms in stateanxiety scores of the STAI. The negative score indicates a lower average score (less anxiety) for the expectant management group, but this was not significant (treatment effect P = 0.09).
Patients randomized to expectant management also showed lower scores on the perinatal grief scale total and its sub-scales (indicating less grief) than patients randomized to curettage, but again the difference did not reach statistical significance (treatment effect P = 0.3).
Preference groups
No statistically significant differences in any of the HRQL measures was observed between women preferring expectant management and those preferring surgical evacuation.
Randomized versus preference groups
In expectantly managed patients, no differences in HRQL measures were found between those treated according to randomized treatment allocation compared with those managed according to their preference. Between women randomized to curettage and women who preferred curettage a significant overall five-point difference (P = 0.03) was found in MCS scores. Women treated according to randomized allocation performed worse than those who received the same treatment at their own request.
Additional analysis
In randomized women no differences were found between the HRQL scores of women allocated to the treatment for which they expressed a slight preference shortly before randomization and those not allocated to their preferred treatment. We also found no differences between the proportion of high responders (i.e. women who returned four or five questionnaires) and low responders (returning two or three questionnaires) in the randomized and in the preference groups.
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Discussion |
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We would conclude that a decreased motivation among women randomized to a moderately non-preferred treatment could not explain the differences between the two randomized groups; HRQL scores did not differ between women who were randomized to their preferred treatment and women who were not. Another explanation for the differences found in mental health scores may be the absence of a treatment option for women randomized to curettage as opposed to women randomized to expectant management, who still have the option to change their mind and have a curettage at a later stage. This escape is far from theoretical as 50% of the women allocated to expectant management took advantage of this option after a waiting period. Although expectant management is less effective than surgical evacuation, a waiting period may prevent many curettages. In our study, 38% of the expectantly managed women miscarried within a week (data not shown). Another study (Nielsen and Hahlin, 1995) reported a lower failure of expectant management. However, in this study most women already had an incomplete miscarriage. A study comparing misoprostol and expectant management (Ngai et al., 2001
) reported a success rate in the misoprostol group versus the expectant group of 83.3 versus 46.3%.
The potential for generalization of a randomized trial may be limited if many patients show an outspoken treatment preference, with consequent refusal to participate in such a study. Usually they receive the treatment of their choice after having been excluded from the trial (Brewin and Bradley, 1989). Our study, including both assignment groups with identical clinical protocol, confirms that providing a free choice of treatment increases the perceived quality of life that comes with it (Henshaw et al., 1993
).
We did not expect the substantially lower mental health scores at inclusion among women preferring surgical evacuation in comparison with all other women. Maybe this reflects the mental attitude and stability required in accepting the uncertainties of expectant management.
The differential response to both treatments has received little attention so far. To our knowledge only one study has compared anxiety and depressive reactions in a randomized trial comparing expectant management and surgical evacuation (Nielsen et al., 1996). That study reported no differences in anxiety or depressive reactions between the treatment groups after a 2 week period. Similarly, we found no differences in anxiety after 2 weeks or at 12 weeks, but we did observe an overall better mental health during the entire 12 week observation period in women allocated to expectant management. This justifies the recommendation of expectant management to those women without strong treatment preferences.
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Acknowledgements |
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Notes |
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References |
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Submitted on October 1, 2001; accepted on January 25, 2002.