Conventional Levels Of Statistical Significance Research Articles

Monetary Incentives for Schizophrenia

BACKGROUND There is evidence suggesting that people with serious mental illness are less responsive to everyday social rewards such as praise. Motivation and performance in social situations can be poor. Rewarding of tasks with money improves motivation to complete the tasks in everyday life. Careful use of targeted monetary rewards could also help people with troublesome symptoms of schizophrenia. OBJECTIVES To assess the effect of monetary incentive/rewards for people with schizophrenia or schizophrenia-like illness. SEARCH STRATEGY We searched the Cochrane Schizophrenia Group's Register (June 2008). SELECTION CRITERIA All relevant randomised controlled trials comparing monetary rewards with standard care or no monetary rewards. DATA COLLECTION AND ANALYSIS Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI). For continuous data we calculated weighted mean differences (MD) and their 95% confidence intervals. MAIN RESULTS Five trials are excluded that investigate one type of monetary reward over another and may be included in a future update. We did include one study, carried out over 40 years ago, randomising a total of 25 very chronically ill people who had been in hospital an average of 20 years. The targeted task that was being encouraged was assembly of dolls. People allocated to the payment group produced less dolls than those not paid at all although this difference did not reach conventional levels of statistical significance (MD -0.80 CI -1.44 to -0.16). AUTHORS' CONCLUSIONS Monetary rewards have been the topic for sporadic evaluative research for decades and this review shows that randomised studies are possible. We suggest a design for a future informative trial.

Monetary incentives for schizophrenia

There is evidence suggesting that people with serious mental illness are less responsive to everyday social rewards such as praise. Motivation and performance in social situations can be poor. Rewarding of tasks with money improves motivation to complete the tasks in everyday life. Careful use of targeted monetary rewards could also help people with troublesome symptoms of schizophrenia. To assess the effect of monetary incentive/rewards for people with schizophrenia or schizophrenia-like illness. We searched the Cochrane Schizophrenia Group's Register (June 2008). All relevant randomised controlled trials comparing monetary rewards with standard care or no monetary rewards. Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI). For continuous data we calculated weighted mean differences (MD) and their 95% confidence intervals. Five trials are excluded that investigate one type of monetary reward over another and may be included in a future update. We did include one study, carried out over 40 years ago, randomising a total of 25 very chronically ill people who had been in hospital an average of 20 years. The targeted task that was being encouraged was assembly of dolls. People allocated to the payment group produced less dolls than those not paid at all although this difference did not reach conventional levels of statistical significance (MD -0.80 CI -1.44 to -0.16). Monetary rewards have been the topic for sporadic evaluative research for decades and this review shows that randomised studies are possible. We suggest a design for a future informative trial.

Nerve Injury in Patients after Hip and Knee Arthroplasties and Knee Arthroscopy

To examine the reporting of lower limb neuropathy within 90 days of surgery for patients undergoing hip arthroplasty, knee arthroplasty, or knee arthroscopy. This was a retrospective study using data from the 1998 MarketScan Commercial Claims and Encounter Database (The MEDSTAT Group) to identify lower limb neuropathy after these surgeries. The sample was selected within the first 9 months of 1998 using International Classification of Diseases, 9th Revision (ICD-9), and Current Procedural Terminology (CPT) codes for hip and knee surgical procedures. Lower limb nerve injuries as determined by ICD-9 codes within 90 days postsurgery were the main outcome measures. The influence of diabetes on the rates of nerve injuries after surgery was also examined. A total of 14,979 patients underwent these surgical procedures, 10 of whom were reported to have sustained a nerve injury postsurgery (0.07%). The sample comprised mainly men (53.1%), and the largest groups consisted of those aged 45-54 yrs (27.0%) and 55-64 yrs (27.7%). Nerve injury occurred at a rate of 0.03% after hip arthroplasty, 0.01% after knee arthroplasty, and 0.02% within 3 mos of arthroscopic knee surgery. Overall, nerve injuries were two times more prevalent in the diabetic vs. nondiabetic population (0.11% vs. 0.06%); however, this difference did not meet conventional levels of statistical significance. Specific to knee arthroplasty, there were 10-fold differences in nerve injury rates between diabetic and nondiabetic patients, 0.11% vs. 0.01%, respectively (P <or= 0.01), although the overall risks were small. Nerve injuries after hip and knee arthroplasty and knee arthroscopy were rare in a large population of patients younger than 65 yrs. Although the overall rates were low, there was an increased occurrence of nerve injuries in the diabetic population. This information is useful when counseling patients and benchmarking surgical complication rates.

Fentanyl vs. pethidine as sedation for gastrointestinal endoscopy: Author’s reply to Hayee et al.

Sirs, On behalf of the authors, I wanted to write and thank Dr Hayee et al.1 for their interest in our paper2 and congratulate them on their recent publication3 in this area. I would concur that the results of the two studies suggest that the use of fentanyl (as opposed to meperidine (pethidine)) may shorten recovery times. While our difference in recovery time between those receiving fentanyl (63 min) and those receiving meperidine (76.2 min) did not reach conventional levels of statistical significance (P value = 0.07), we do believe that this factor was the main driver of shorter total procedure times observed in our study. Our study size was driven by power calculation. We sought to detect a 10-min difference in total procedure time comparing the two narcotics. The study was not powered to look separately at colonoscopy or oesophagogastroduedonoscopy (EGD) and so it is not surprising that we did not find a statistical difference in procedure time in this subgroup analysis (likely beta error). The trends in both total procedure time and recovery time were similar (favouring fentanyl) across both EGD and colonoscopy suggesting that the observed pharmacological effect was present irrespective of the procedure. Certainly, you could argue that EGD does not require narcotics. Our institutional practice is to combine a narcotic with midazolam for EGD and so that is what we studied. The specifics of how the narcotic and midazolam were dosed are outlined in the methods. There was no standardization. The dosing of the unit equivalents of narcotics or midazolam were left ‘solely to the discretion of the endoscopist based on the patient’s clinical status’. The reported mean doses of narcotic used represent cumulative dose given during the procedures. Finally, with regard to assessment of discomfort, we simply assessed patient pain by VAS score. We could not use nursing assessment of pain as they were not blinded to treatment allocation. Declaration of personal and funding interests: None.

The Role of Interpersonal and Social Rhythm Therapy in Improving Occupational Functioning in Patients With Bipolar I Disorder

Recent studies demonstrate the poor psychosocial outcomes associated with bipolar disorder. Occupational functioning, a key indicator of psychosocial disability, is often severely affected by the disorder. The authors describe the effect of acute treatment with interpersonal and social rhythm therapy on occupational functioning over a period of approximately 2.5 years. Patients with bipolar I disorder were randomly assigned to receive either acute and maintenance interpersonal and social rhythm therapy, acute and maintenance intensive clinical management, acute interpersonal and social rhythm therapy and maintenance intensive clinical management, or acute intensive clinical management and maintenance interpersonal and social rhythm therapy, all with appropriate pharmacotherapy. Occupational functioning was measured with the UCLA Social Attainment Scale at baseline, at the end of acute treatment, and after 1 and 2 years of maintenance treatment. The main effect of treatment did not reach conventional levels of statistical significance; however, the authors observed a significant time by initial treatment interaction. Participants initially assigned to interpersonal and social rhythm therapy showed more rapid improvement in occupational functioning than those initially assigned to intensive clinical management, primarily accounted for by greater improvement in occupational functioning during the acute treatment phase. At the end of 2 years of maintenance treatment, there were no differences between the treatment groups. A gender effect was also observed, with women who initially received interpersonal and social rhythm therapy showing more marked and rapid improvement. There was no effect of maintenance treatment assignment on occupational functioning outcomes. In this study, interpersonal and social rhythm therapy, with its emphasis on amelioration of interpersonal and role functioning, improved occupational functioning significantly more rapidly than did a psychoeducational and supportive approach with no such emphasis on functional capacities.

The Effect of OPC Factor™ on Energy Levels in Healthy Adults Ages 45–65: A Phase IIb Randomized Controlled Trial

To determine the efficacy of the food supplement OPC Factor to increase energy levels in healthy adults aged 45 to 65. Randomized, placebo-controlled, triple-blind crossover study. Twenty-five (25) healthy adults recruited from the University of Pennsylvania Health System. OPC Factor,trade mark (AlivenLabs, Lebanon, TN) a food supplement that contains oligomeric proanthocyanidins from grape seeds and pine bark along with other nutrient supplements including vitamins and minerals, was in the form of an effervescent powder. The placebo was similar in appearance and taste. Five outcome measurements were performed: (1) Energy subscale scores of the Activation-Deactivation Adjective Check List (AD ACL); (2) One (1) global question of percent energy change (Global Energy Percent Change); (3) One (1) global question of energy change measured on a Likert scale (Global Energy Scale Change); 4. One (1) global question of percent overall status change (Global Overall Status Percent Change); and (5) One (1) global question of overall status change measured on a Likert scale (Global Overall Status Scale Change). There were no carryover/period effects in the groups randomized to Placebo/Active Product sequence versus Active Product/Placebo sequence. Examination of the AD ACL Energy subscale scores for the Active Product versus Placebo comparison revealed no significant difference in the intention-to-treat (IT) analysis and the treatment received (TR) analysis. However, Global Energy Percent Change (p = 0.06) and Global Energy Scale Change (p = 0.09) both closely approached conventional levels of statistical significance for the active product in the IT analysis. Global Energy Percent Change (p = 0.05) and Global Energy Scale Change (p = 0.04) reached statistical significance in the TR analysis. A cumulative percent responders analysis graph indicated greater response rates for the active product. OPC Factor may increase energy levels in healthy adults aged 45-65 years. A larger study is recommended. Clinical Trials.gov identifier: NCT03318019.

Educational effects of the Tools of the Mind curriculum: A randomized trial

The effectiveness of the Tools of the Mind (Tools) curriculum in improving the education of 3- and 4-year-old children was evaluated by means of a randomized trial. The Tools curriculum, based on the work of Vygotsky, focuses on the development of self-regulation at the same time as teaching literacy and mathematics skills in a way that is socially mediated by peers and teachers and with a focus on play. The control group experienced an established district-created model described as a “balanced literacy curriculum with themes.” Teachers and students were randomly assigned to either treatment or control classrooms. Children (88 Tools and 122 control) were compared on social behavior, language, and literacy growth. The Tools curriculum was found to improve classroom quality and children's executive function as indicated by lower scores on a problem behavior scale. There were indications that Tools also improved children's language development, but these effects were smaller and did not reach conventional levels of statistical significance in multi-level models or after adjustments for multiple comparisons. Our findings indicate that a developmentally appropriate curriculum with a strong emphasis on play can enhance learning and development so as to improve both the social and academic success of young children. Moreover, it is suggested that to the extent child care commonly increases behavior problems this outcome may be reversed through the use of more appropriate curricula that actually enhance self-regulation.

An examination of risky sexual behavior and HIV in victims of child abuse and neglect: A 30-year follow-up.

This article examined links between childhood maltreatment and risky sexual behavior (early sexual contact, promiscuity, prostitution) and HIV in adulthood. Using a prospective cohort design, physically and sexually abused and neglected children (ages 0-11) with documented cases during 1967-1971 were matched with nonmaltreated children and followed into adulthood. Early sexual contact, promiscuity, and prostitution were assessed through in-person interviews and official records (prostitution) at approximate age 29 (N=1196). HIV tests were conducted at approximate age 41 (N=631). Child maltreatment was associated with prostitution (OR=2.47, 95% CI=1.35-4.50) and early sexual contact (OR=1.73, 95% CI=1.24-2.40). Prevalence of HIV in the abuse/neglect group was twice that in controls (OR=2.35, 95% CI=.64-8.62), although this difference did not reach conventional levels of statistical significance. SEM provided significant support for a model linking child abuse and neglect to prostitution through early sexual contact and a marginal link to HIV through prostitution. These findings provide prospective evidence that maltreated children are more likely to report sexual contact before age 15, engage in prostitution by young adulthood, and test positive for HIV in middle adulthood.

Maternal self-esteem, exposure to lead, and child neurodevelopment

The notion that maternal personality characteristics influence cognitive development in their children has been grounded in stress moderation theory. Maternal personality traits, such as self-esteem, may buffer maternal stressors or lead to improved maternal–child interactions that directly impact neurodevelopment. This can be extended to suggest that maternal personality may serve to attenuate or exacerbate the effects of other neurotoxicants, although this has not been studied directly. We examined whether mothers’ self-esteem had a direct or main effect on their children's cognitive outcomes. We also explored the modifying effects of maternal self-esteem on the association between exposure to lead and neurodevelopment in these children. Study participants included 379 mother–child pairs from Mexico City. Data included the Coopersmith Self-Esteem Scale in mothers, children's Bayley's Scale of Infant Development (BSID) scores, and sociodemographic information. Linear regression was used to model the relationship between maternal self-esteem and the Bayley's Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores at age 24 months using models stratified by levels of maternal self-esteem. In adjusted models, each point increase in maternal self-esteem was associated with children having 0.2 higher score on the Bayley's MDI ( p = 0.04). Similar results were observed using the PDI outcome. Moreover, there was evidence that maternal self-esteem attenuated the negative effects of lead exposure, although the interaction fell short of conventional levels of statistical significance.

Acupuncture for Blood Pressure Lowering

Blood pressure–related disease remains a major public health problem in developed and developing countries alike. The Global Burden of Disease study estimates 62% of stroke, 49% of ischemic heart disease, and 14% of other cardiovascular disease can be attributable to mean systolic blood pressure levels >115 mm Hg worldwide.1 The mainstay of medical management of hypertension is a number of commonly used drugs,2 the mechanisms of action of which are well understood and grounded in conventional science. However, despite the strength of evidence supporting the efficacy of these agents and their wide endorsement in national and international guidelines, only about one half of those patients in whom treatment is indicated are compliant with drug therapy. Treatment cost, adverse effects, and complexity are commonly cited barriers to patient adherence,3,4 and such factors undoubtedly play an important role in the growing interest in alternative therapies for blood pressure control. Article p 3121 Acupuncture, one of the oldest and most commonly used forms of alternative medicine, has existed for >2500 years. In traditional acupuncture, fine needles are inserted into precisely defined, specific points on the body, each of which has distinct therapeutic actions.5 For a long time, acupuncture was viewed by practitioners of Western medicine as “the Chinese equivalent of voodoo,”6 but certain events encouraged wider acceptance of this form of treatment beginning in the 1970s. One such event is said to have been President Richard Nixon’s goodwill visit to China in 1972 during which he saw acupuncture in practice. His personal physician subsequently wrote, “I have seen acupuncture work.” This statement not only increased public interest but also encouraged key figures in the medical community to travel to China to develop a …

A randomised trial of two methods of issuing prenatal test results: the ARIA (Amniocentesis Results: Investigation of Anxiety) trial

Many pregnant women experience anxiety while waiting for the results of diagnostic tests. Policies and practices intended to reduce this anxiety require evaluation. To test the following two hypotheses: * That giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued "when available" (i.e. variable date). * That issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. A multicentre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. The prenatal diagnosis clinics in 12 hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. Two hundred and twenty-six women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available. Issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Anxiety 1 month after receiving karyotype results, measured using the short form STAI. Issuing early results from a partial but rapid test reduced maternal anxiety by a clinically significant amount during the waiting period (mean daily score 12.5 versus 14.8; scale score difference -2.36, 95% CI -1.2, -3.6), compared with receiving only the full karyotype results. There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period (mean daily score 13.2 versus 14.2; scale score difference -1.02, 95% CI -2.2, 0.2). One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results tended to be more anxious than those who had not (mean single day score 9.2 versus 8.3; mean scale score difference 0.95, 95% CI -0.03, 1.9). This small to moderate effect did not reach conventional levels of statistical significance. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. Because there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them.

Meta-Analysis in Genome-Wide Association Datasets: Strategies and Application in Parkinson Disease

BackgroundGenome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques.Methodology/Principal FindingsBoth single and two-stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I2 = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets).Conclusions/SignificanceMeta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies.

Facilitating research participation and improving quality of life for African American prostate cancer survivors and their intimate partners

African American men experience worse prostate cancer outcomes compared with those of Caucasian men, not only in incidence and mortality rates, but also in coping with the side effects of treatment. Unfortunately, African American men have been significantly under-represented in research evaluating the efficacy of psychosocial interventions for improving coping in prostate cancer survivors. This pilot study explored the feasibility and efficacy of coping skills training (CST), an intervention developed to enhance coping with treatment side effects in a sample of African American prostate cancer survivors and their intimate partners. The intervention was delivered in a telephone-based format designed to facilitate research participation. A total of 40 couples were randomized to either 6 sessions of CST or usual care. Survivors completed measures of disease-specific quality of life (QOL) related to urinary, sexual, bowel, and hormonal symptom domains, as well as measures of global QOL (i.e., physical functioning and mental health). Partners completed measures of caregiver strain, mood, and vigor. Analysis of data from 30 couples (12 couples in CST, 18 couples in usual care) indicated that CST produced moderate to large treatment effects for QOL related to bowel, urinary, sexual, and hormonal symptoms. Partners who underwent CST reported less caregiver strain, depression, and fatigue, and more vigor, with moderate effect sizes observed that approached conventional levels of statistical significance. These preliminary findings suggest that telephone-based CST is a feasible approach that can successfully enhance coping inAfrican American prostate cancer survivors and their intimate partners. Cancer 2007. (c) 2006 American Cancer Society.

The Cost-Effectiveness of Cognitive Behavior Therapy for Borderline Personality Disorder: Results from the BOSCOT Trial

Borderline personality disorder places a significant burden on healthcare providers and other agencies. This study evaluated the cost-effectiveness of cognitive behavior therapy plus treatment as usual compared to treatment as usual alone for patients with borderline personality disorder. The economic analysis was conducted alongside a multi-center, randomized controlled trial. The costs of primary and secondary healthcare utilization, alongside the wider economic costs, were estimated from medical records and patient self-report. The primary outcome measure used was the quality-adjusted life year (QALY), assessed using EuroQol. On average, total costs per patient in the cognitive behavior therapy group were lower than patients receiving usual care alone (-689 pounds sterling), although this group also reported a lower quality of life (-0.11 QALYs). These differences were small and did not approach conventional levels of statistical significance. The use of cognitive therapy for borderline personality disorder does not appear to demonstrate any significant cost-effective advantage based on the results of this study.

A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial

Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies — the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.

Incorporating Carer Effects into Economic Evaluation

Despite great interest in the development of methods used in the economic evaluation of health technologies, the effects of carer costs and quality of life (QOL) on the cost effectiveness of treatments has not been widely explored. Yet carer effects are clearly evident in the literature and relevant to the perspective of many published economic evaluations. To examine whether patient QOL is associated with carer time and carer QOL. We used two datasets to investigate carer effects. Firstly, we used 40,312 cases from the Health Outcomes Data Repository (HODaR) to assess the relationship between patient utility, using the EuroQoL (EQ)-5D, and the number of days care needed from friends and relatives. The stability of the relationship across patient subgroups was assessed by replicating the analysis in ten disease groups. Secondly, we used 64 cases from a study of patients with Alzheimer's disease and their primary carer. These data allowed us to estimate the relationships between patient and carer utility, using the EQ-5D, and patient utility and carer burden using the Community Dementia Quality of Life Profile (CDQLP). For carer time, a linear model showed that each 0.1-point reduction in patient utility was associated with a 2.5-day increase in carer time over a 6-week period. A more general model, based on EQ-5D domain scores, was better specified and showed that decreased functioning within each domain is associated with increased carer time. Problems with self-care and usual activities have the greatest impact on carer time. These models do not appear to be stable across different disease groups. For carer utility, the relationships between carer and patient utility have low explanatory power and are poorly specified. A clearer relationship is shown between carer burden and utility, such that when sociodemographic covariates are introduced, the relationship reaches conventional levels of statistical significance (p < 0.05). The preliminary work described here shows that improving patient QOL may reduce the need for carer time and improve carer QOL. Incorporating such effects into economic evaluations will change cost-per-QALY estimates, with the size of reduction dependent on the domains of health affected by treatment. Clinical studies need to capture carer data so that we can better understand these effects, and how they impact on economic evaluation.

Socio‐economic position across the life course and hysterectomy in three British cohorts: a cross‐cohort comparative study

To examine the association between indicators of lifetime socio-economic position and rates of hysterectomy in three British cohorts. Cross-cohort comparative study. Two cohorts: England, Scotland and Wales. Third cohort: Aberdeen, Scotland. Three thousand two hundred and eight women born between 1919 and 1940, participating in the British Women's Heart and Health Study (BWHHS); 1394 women from the MRC National Survey of Health and Development (NSHD), followed up since birth in 1946; 3208 women born between 1950 and 1955, participating in the Aberdeen Children of the 1950s study, all with complete information on lifetime socio-economic position and hysterectomy status. Relative indices of inequality were derived for markers of socio-economic position in childhood and adulthood. Cox's regression models were used to test the association between these markers and hysterectomy. Self-reported hysterectomy with or without oophorectomy. Adverse socio-economic position in childhood and as indicated by educational status was associated with reduced rates of hysterectomy in the oldest of the three cohorts (BWHHS), whereas conversely in the NSHD and Aberdeen cohorts it was associated with increased rates of hysterectomy. The unadjusted hazards ratios for hysterectomy comparing worst to best socio-economic position for father's social class were 0.73 (0.56, 0.96) for women from the BWHHS, 1.77 (1.19, 2.65) for those from the NSHD and 2.06 (1.46, 2.89) for those from the Aberdeen cohort. Associations between markers of adult socio-economic position and hysterectomy tended to be weaker in all three cohorts and often did not reach conventional levels of statistical significance. Our results show that hysterectomy rates are influenced by childhood socio-economic position and educational attainment, but that the nature of this association varies across these three British cohorts born in different decades of the 20th century. That there were no consistent or strong associations between adult SEP and hysterectomy rates suggest that social factors influencing rates of hysterectomy are likely to be those experienced or which develop in early life rather than those which develop later.

The efficacy of acupressure bands in reducing radiation therapy-induced nausea is enhanced when combined with expectancy enhancing information

8158 Background: Mounting evidence suggests that patients’ expectancies relating to nausea development are significant predictors of, and likely, contributing factors to treatment-related nausea. Expectancy is also theorized to be the primary factor accounting for efficacy of alternative therapies such as acupressure bands. Methods: Patients with nausea from radiation therapy were randomized to either standard care (Arm 1), standard care plus acupressure bands plus a handout conveying information not intended to enhance efficacy expectations (Arm 2), or standard care plus acupressure bands plus information designed to enhance efficacy expectations (Arm 3). Prior to randomization, patients reported nausea (on a 7-point semantic rating scale, 1 = “not nauseated” to 7 = “extremely nauseated”) during four time periods (evening and night on the day of treatment, and morning and afternoon of the following day). The four nausea reports were then averaged to create a single score. Post-intervention nausea was assessed in a similar fashion. Results: 63 Patients (female = 37, mean age = 53.3 years) provided evaluable data. The 15 patients randomized to Arm 1 had a small (8%) increase in average nausea. The 26 patients randomized to Arm 2, by contrast, had a modest (15%) decrease in average nausea. A much larger (23%) reduction of nausea occurred in the 22 patients randomized to Arm 3. We used analysis of covariance, controlling for gender, to examine the nausea change scores (post intervention nausea minus baseline nausea) among treatment arms. The overall group difference closely approached conventional levels of statistical significance, P < .08, and the linear contrast was statistically significant, P < .03. Estimated marginal means of the change score for the three groups were: Arm 1 = 0.21, Arm 2 = -0.38, Arm 3 = -0.82. Conclusions: Non-pharmacological interventions that positively affect nausea expectancies have the promise of adding substantially to nausea control. Supported by ACS grant RSG-01–071-PBP No significant financial relationships to disclose.

Fluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing (MRC FOCUS): A 2135-patient randomized trial in advanced colorectal cancer (ACRC)

3518 Background: This multicenter, open randomized trial assesses the effect on overall survival (OS) and quality of life of the planned sequencing of the first two cytotoxic drugs (fluorouracil (FU) plus one other) received by patients (pts) with inoperable ACRC. It compares three approaches: sequential single agents (FU first then change to second drug); sequential single/combination (FU then add a second drug); or 1st-line combination. It also compares irinotecan (Ir) and oxaliplatin (Ox) combinations. Methods: Pts had PS 0–2; GFR >50; ALP <5 x ULN; bili <1.25 x ULN. Randomization was 2:1:1:1:1 to: Plan A (reference): MdG (Modified de Gramont: leucovorin; FU bolus + 48 hr infusion; q2w) until treatment failure, then 2nd-line Ir; Plans Bir and Box: MdG until treatment failure, then 2nd-line IrMdG or OxMdG respectively; Plans Cir and Cox: 1st-line IrMdG or OxMdG. Primary endpoint was OS, 2100 pts giving 80% power (α = 0.01) to detect a difference of 22.5% vs 15% in 2 yr OS of each plan against Plan A. Results: 2135 pts entered, May’00 - Dec’03, at 61 centres, median age 64 yrs; 92% PS 0–1. With 1435 deaths to date, the primary comparisons, of OS for each plan (Bir, Box, Cir, Cox) versus Plan A, show trends to improvement (HR 0.92, 0.91, 0.86, 0.96 respectively) but all are non-significant (all p > 0.05). Grouped comparison of OS in Plans B (712 pts) with Plan A (710 pts) has a HR of 0.91, 95% CI (0.81, 1.04) p=0.157 in favour of B. The comparison of OS in grouped Plans C (713 pts) with Plan A has a HR of 0.91 (0.80, 1.03) p=0.134 favouring C. Comparison of Plans B with Plans C has a HR of 1.00 (0.88, 1.14) p=0.993. OS does not differ significantly between Ox and Ir in plans B and C. Compared with Plan B, Plan C gave a higher 1st-line RR (54% vs 29%) and PFS (median 8.7 vs 6.6 months) but shorter time to failure of the Plan (median 9.1 vs 11.6 months) (all p<0.001). Conclusions: Slightly increased survival was seen with combination chemotherapy, whether given 1st line or 2nd line, but this does not reach conventional levels of statistical significance. However, 1st-line combination chemotherapy did not improve OS compared with the same combinations deferred until 2nd line. Mature data will be presented at the meeting. No significant financial relationships to disclose.

Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]). Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.