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Influence of Stroke Survivor Characteristics and Family Conflict Surrounding Recovery on Caregivers’ Mental and Physical Health Patricia C. Clark ▼ Sandra B. Dunbar ▼ Cleveland G. Shields Bindu Viswanathan ▼ Dawn M. Aycock ▼ Steven L. Wolf       406 Background: Stroke recovery is a dynamic process for stroke survivors, and shorter lengths of stay in healthcare settings shift the care of the survivors to family caregivers. The physical and mental sequelae after stroke and the family’s response to this catastrophic event may have deleterious effects on caregivers. Objective: To examine the influence of stroke survivors’ motor function, their memory and behavior changes, and the family conflict surrounding stroke recovery on the mental and physical health of caregivers during the subacute recovery period. Methods: This cross-sectional, correlational study used baseline data from family caregivers (n ⫽ 132) and first-time stroke survivors enrolled in a larger multisite study. Results: The caregivers were primarily White (71%), female (74%), college-educated (73%) spouses (80%) of survivors. Most of the caregivers (66%) reported family conflict. The caregivers from families with lower family functioning scores reported worse mental health. The caregivers reported lower mental health when they were caring for stroke survivors with a combination of high memory/behavior changes and low motor function (R² ⫽ .30). Family conflict appears to exacerbate the impact of memory and behavior changes on caregiver mental health. Higher caregiver education and no major health problems were associated with better caregiver physical health (R² ⫽ .36). Caregiver physical health was not associated with family functioning or stroke survivor memory and behavior changes. Conclusions: These results indicate that memory and behavior changes of stroke survivors and family conflict surrounding stroke recovery are important considerations for assessment during the poststroke recovery period. Key Words: caregivers 䡠 family 䡠 stroke S troke recovery is a dynamic process for stroke survivors, primary caregivers, and their families. In the current healthcare environment, stroke survivors experience decreased lengths of stay in acute and rehabilitation settings (Dobkin, 1995), which shifts a greater responsibility for care to the family early in the recovery process. The emotional and tangible support that a family provides a member with a serious illness is substantial, and the impact on the family can be considerable (Ell, 1996). The influence of the stroke survivors’ specific problems and the family context on caregiver outcomes is unclear. In general, the vast majority of disabled older adults in a community rely on one or more family members who provide some assistance. However, family caregivers of stroke survivors often experience negative personal outcomes from caregiving (Bugge, Alexander, & Hagen, 1999; Draper, Poulos, Cole, Poulos, & Ehrilich, 1992; Greveson, Gray, French, & James, 1991; King, Shade-Zeldow, Carlson, Feldman, & Philip, 2002). Such negative consequences may be attributable to inadequate caregiver knowledge and skills, lack of family support, or characteristics of the stroke survivor. Documented outcomes for stroke family caregivers have shown significant mental distress at levels equivalent to that experienced by caregivers of patients with Alzheimer’s disease (Clark & King, 2003; Patricia C. Clark, PhD, RN, FAHA, is Assistant Professor; Sandra B. Dunbar, RN, DSN, FAAN, is Professor; and Dawn M. Aycock, MSN, RN, is Research Nurse, Sr, Emory University, Atlanta, Georgia. Cleveland G. Shields, PhD, is Associate Professor, University of Rochester, New York. Bindu Viswanathan, PhD, is Assistant Professor, School of Public Health, Emory University, Atlanta, Georgia. Steven L. Wolf, PhD, PT, FAPTA, is Professor, Department of Rehabilitation Medicine, Emory University, Atlanta, Georgia. Nursing Research November/December 2004 Vol 53, No 6 Nursing Research November/December 2004 Vol 53, No 6 Poststroke Influences on Caregivers’ Health 407 Draper et al., 1992). Caregivers also son et al., 1991; Thompson, Bundiek, may be physiologically vulnerable as a & Sobolew-Whubin, 1990). Emerging result of their caregiving role (Bugge et neurorehabilitation interventions, such al., 1999; Schulz, Visintainer, & as constraint-induced therapy to remeWilliamson, 1990; Wright, Clipp, & diate stroke survivors’ physical disabilGeorge, 1993). Facilitating caregivers’ ities, require substantial family supThe vast majority of adjustment to their roles is essential for port. Research should be conducted to disabled older adults in a improvement in quality of life for careexamine the impact of this increased givers and stroke survivors. family burden on the mental and physcommunity rely on one or Although high levels of social supical health of caregivers. more family members who port have been associated with faster The conceptual framework for this provide some assistance and more extensive stroke survivor study was the strength–vulnerability recovery (Glass, Matchar, Belyea, & model (Figure 1) (Shields, King, & Feussner, 1993; Tsouna-Hadjis, VemWinn, 1995) developed from a family mos, Zakopoulos, & Stamatelopoulos, systems life cycle approach to family 2000), family relationships deteriorate therapy. As portrayed by this model, the after stroke (Anderson, Linto, & Stewinteraction of family members influart-Wynne, 1995; King et al., 2002). ences the caregiver and, depending on Family functioning has been identified as a critical variable the type of interaction, the family may increase or decrease in stroke research (Bishop & Evans, 1995). Ineffective stress for the caregiver. During their life cycle, families may family functioning has been associated with worse careexperience predictable or unpredictable events (e.g., stroke) giver adjustment (Evans, Bishop, & Ousley, 1992). Anderresulting in gain or loss to the family system. son et al. (1995) found that caregivers reporting adverse The strength–vulnerability framework has four major effects on families of stroke survivors attributed the effects factors that influence an individual’s functioning: strength to tension in the families, misunderstandings, and the carefactors, vulnerability factors, risk factors, and healthgivers’ displacement of their anger about the situation to enhancing factors. Strengths are conceptualized as the others in the family. Caregivers may experience high levels internal processes or factors that foster healthy functionof family conflict, and this conflict may be associated with ing. The ability of the family to function and cope with the worse caregiver outcomes. Examining family conflict stroke event and the recovery process is identified as a famspecifically related to stroke recovery rather than general ily strength. The strength of the family is conceptualized as family functioning may provide more information for the overall family functioning, which has developed over the development of effective interventions. lifetime of the family. Vulnerabilities result from an event The residual effects of a stroke often are manifested that increases the chances of poor psychological outcomes. through changes in the stroke survivor’s memory and Changes in biologic health, such as stroke impairments of behavior as well as changes in physical function. Research physical function, and the memory–behavior problems has been focused primarily on physical recovery from that may be associated with stroke are vulnerability factors stroke, with less emphasis on the cognitive–behavioral for individuals and families. These changes may reduce the deficits and how these may influence stroke survivor funcindividual’s capacity to participate in the family. Risk factional recovery. The initial severity of stroke disability is tors are external factors such as education and gender that the strongest predictor of subsequent functional recovery increase the chances of negative outcomes. (Stineman & Granger, 1998), but the effects of other variThe purpose of this study was to examine the influence ables such as cognitive, psychological, and social problems of risk factors and vulnerabilities (stroke survivors’ charhave not been determined (Riddoch, Humphreys, & Bateacteristics and family conflict surrounding stroke recovery) man, 1995). Cognitive deficits after stroke have been on the mental and physical health of caregivers during the reported for approximately 35% of patients (Tatemichi et subacute recovery period. al., 1994), with depression and anxiety described as the “neglected” outcomes of stroke (Mayo, 1998). Memory Participants, Settings, and Methods and behavior changes of stroke survivors have a negative Eligibility Criteria impact on caregiver outcomes (Bugge et al., 1999; Schulz, This study was complementary to a national, multisite, Tompkins, & Rau, 1988), but the relative influence of randomized clinical trial to test constraint-induced therapy these changes on caregivers’ mental and physical health for recovery of upper extremity function (EXCITE) (Winhas been understudied. stein et al., 2003). The study was approved by institutional Empirical evidence indicates that stroke survivors’ review boards at participating sites, and informed consent memory and behavior changes and family functioning are was obtained for all the participants. Eligible family careassociated with caregivers’ health (Clark & King, 2003; givers were individuals caring for a stroke survivor Schulz et al., 1988). However, studies are limited, and enrolled in the EXCITE clinical trial who were 18 years of these relations have varied at different points in the recovage or older, able to read and speak English, not currently ery process. Evidence about the relation of stroke surundergoing treatment (medication or counseling) for vivors’ physical, memory, and behavior changes on caredepression, and self-identified as providing the most assisgivers’ outcomes is conflicting also (Dennis, O’Rourke, tance to the stroke survivor during recovery. Lewis, Sharp & Warlow, 1998; Draper et al., 1992; Greve- 408 Poststroke Influences on Caregivers’ Health Nursing Research November/December 2004 Vol 53, No 6 FIGURE 1. Strength–Vulnerability model for caregiving. SS, stroke survivor Stroke survivors met extensive eligibility criteria for the EXCITE trial (Winstein et al., 2003), which required them to be 3 to 9 months post a first-time clinical cerebrovascular accident (ischemic or hemorrhagic), specific active range-of-motion criteria for wrist movement, and a MiniMental State examination score of 24 or higher. Research Setting and Design This study was conducted at five sites across the United States (six rehabilitation centers) that were locations for EXCITE. Once a stroke survivor was enrolled in the EXCITE trial, caregivers were asked about their willingness to participate in the study. Trained research assistants collected data through in-person administration of questionnaires. In a nonrandom sample, factors associated with caregiver outcomes were examined using a correlational cross-sectional design. Data reported are from baseline, and therefore not affected by the EXCITE intervention. Instruments Caregivers’ mental and physical health were measured with the Medical Outcomes Study Short Form 36, Version 2 (SF-36v2) questionnaire (Ware, Kosinski, & Keller, 1994), a well-established measure for health status. The SF-36v2 is a 36-item, self-report questionnaire from which two primary components are calculated: a physical component scale (PCS) and a mental component scale (MCS). The reliabilities of the PCS and MCS were acceptable, as demonstrated by Cronbach’s alphas of .94 and .88, respectively. The PCS and MCS scores are standardized to the general U.S. population, allowing for norm-based interpretation. Higher scores indicate better mental and physical health. Stroke survivors’ motor function was measured using the Wolf Motor Function Test (WMFT), which uses a timebased method to evaluate upper extremity performance of patients with stroke and traumatic brain injury (Wolf et al., 2001). The WMFT involves strength and timed performance measures and quality of motor function. The average performance time (seconds) required for completion of 15 various tasks using the more affected arm was used to quantify stroke survivors’ motor function. The WMFT has demonstrated reliability and good clinometric properties for the stroke population (Morris, Uswatte, Crago, Cook, & Taub, 2001; Wolf et al., 2001). The Memory and Behavior Problems Checklist (MBPC) (Zarit & Zarit, 1990) was slightly modified to reflect behaviors relevant to stroke and used to measure stroke survivors’ memory and behavior changes. The 19item scale includes a wide array of memory and behavior items. The frequency of memory and behavior problems is rated on a Likert-type scale with a range of 0 (not having occurred) to 3 (occurring daily). The MBPC internal consistency reliability coefficient was .73. The 12-item General Family Functioning scale from the McMaster Family Assessment Device was used to measure general family functioning. This scale has established cutoff scores to enable interpretation of the data for family functioning as “effective” or “ineffective” (Miller, Epstein, Bishop, & Keitner, 1985). The Family Assessment Device, recommended as an assessment measure for families of stroke survivors, has had extensive psychometric testing for adequate reliability and validity in a variety of populations (Epstein, Baldwin, & Bishop, 1983; King et al., 2002). Higher scores indicate ineffective family functioning. The internal consistency reliability coefficient for the General Family Functioning scale was .88. Poststroke Influences on Caregivers’ Health 409 Nursing Research November/December 2004 Vol 53, No 6 The Family Caregiver Conflict Scale for Stroke is a 15item Likert-type scale developed to measure family conflict surrounding stroke recovery. Content reliability and validity were established by Clark, Shields, Aycock, and Wolf (2003). Participants indicate their agreement with the item using a scale of 1 (not true at all) to 7 (very true). Higher scores represent higher levels of conflict within a family. The internal consistency reliability coefficient for the Family Caregiver Conflict Scale for Stroke was .94. Demographic data for stroke survivors and caregivers, such as age and education, were collected. Caregivers were asked about major health problems, and their responses were coded dichotomously as “no major health problem” or “at least one major health problem.” Statistical Analyses Descriptive statistics were computed to characterize the sample and describe major study variables. Before additional analysis was conducted, scatter plots and descriptive statistics were used to examine the data for outliers and distributional characteristics. The distributions of PCS and MCS were slightly skewed. The assumptions of normality for the error terms in the model and the constancy of their variance were checked for each of the two dependent variables in the final model. It was determined that the error distribution was normal, and that there was no deviation from the assumption of constant error variance. The models also were examined using log transformations of PCS and MCS, and the results were found to be similar. Therefore, the nontransformed results are reported. In addition, the correlations between predictor variables were examined for multicollinearity. On the basis of the conceptual model, hierarchical regression was used to examine the association of stroke survivor motor and mental function and family conflict with caregiver mental and physical health, with control used for caregiver characteristics and general family functioning. Data were missing on one or more variables for a few caregivers or stroke survivors. Therefore, regression analyses were performed for 128 caregivers. Subsequently, all possible pairs of interaction effects were explored, and significant interactions were retained in the model. Results At the time of the analysis, 183 stroke survivors were enrolled in the EXCITE trial. Of these stroke survivors, 16 reported not having a caregiver. After 13 caregivers were excluded, 154 caregivers eligible for participation remained, 19 of whom declined participation. Three caregivers were inaccessible at the time of study enrollment. Consequently, a total of 132 caregivers were enrolled in the study. The characteristics of the caregivers are presented in Table 1. They ranged in age from 25 to 85 years (mean, 56.68 ⫾ 13.71 years) and were primarily female, White, non-Hispanic, college-educated, employed spouses or significant others of the stroke survivors. The stroke survivors were 3 to 9 months poststroke and had a mean age of 62.21 ⫾ 12.59 years (range, 30 to 83 years). They were mostly male (64%), primarily White, non-Hispanic (74%), and well-educated (63% had more TABLE 1. Characteristics of Caregivers (N ⫽ 132) Variables Gender Female Male Race White, not Hispanic Black, not Hispanic Hispanic Asian/Multi-ethnic Relationship Spouse/significant other Nonspouse Marital status Married Not married Education High school or less More than high school Incomea ⱕ $30,000 ⱖ $31,000 Employment Full time/part time Retired, homemaker, or other Major health problems No Yes an n (%) 98 (74) 34 (26) 94 (71) 26 (20) 5 (4) 7 (5) 106 (80) 26 (20) 117 (89) 15 (11) 35 (27) 97 (73) 41 (35) 77 (65) 68 (52) 64 (48) 78 (59) 54 (41) ⫽ 118. than a high school education). Most of the stroke survivors had sustained an ischemic (88%) rather than a hemorrhagic stroke (12%). Whereas 57% of the stroke survivors had right hemisphere involvement, 43% had an infarct to the left hemisphere. On the average, caregivers reported healthy family functioning, and showed lower scores on the General Family Functioning scale. However, 32% had scores above the cutoff point (⬎2) for ineffective family functioning (Table 2). A score of 15 on the Family Caregiver Conflict Scale for Stroke indicates no family conflict surrounding recovery. Some level of family conflict (⬎15) was reported by 66% of the caregivers. The mean WMFT score for stroke survivors identified at entry into the study as low functioning (less hand and wrist movement) was 54.89 ⫾ 33.24, as compared with high functioning 15.98 ⫾ 17.06 (t ⫽ 6.70; p ⱕ .01). The average number of memory and behavior changes reported by the caregivers was 7.7 ⫾ 3.6. 410 Poststroke Influences on Caregivers’ Health Nursing Research November/December 2004 Vol 53, No 6 An additional significant interaction between stroke survivors’ memory and behavior changes and family conflict was obtained (Table 3 and Figure 3). Caregivers of stroke survivors with low memory and behavior changes in the presence of high family conflict levels reported mental health scores similar to the scores of those caring for stroke survivors with high memory and behavior problems regardless of the family conflict level. Associations with caregiver physical health (Table 4) differed from associations with caregiver mental health. The only variables associated with caregiver physical health were caregiver education and health problems. Caregivers with lower education and a major health problem reported lower physical health. TABLE 2. Description of Instruments Instruments Caregiver Physical Health Caregiver Mental Health General Family Functioning Family Caregiver Conflict Stroke Survivor Memory and Behavior Frequency Stroke Survivor Motor Function Possible Range ␣ 52.1 (8.8) 48.2 (10.7) 1.8 (0.5) 23.3 (16.7) 0–100 0–100 1–4 15–105 .94 .88 .88 .94 18.1 (10.4) 26.7 (28.5) 0–76 1–120 .73 — Mean (SD) Discussion The results of the regression analysis are shown in Table 3. Of the variables controlled in the first step, only General Family Functioning was significant in the final model, indicating that families with ineffective family functioning are associated with worse caregiver mental health. There was a significant interaction of stroke survivors’ motor function and changes in memory and behavior, indicating that low motor function alone is not associated with worse mental health, but that low motor function with high memory and behavior changes is associated with worse caregiver mental health. This interaction is illustrated in Figure 2. Low motor function with low memory and behavior changes in stroke survivors resulted in caregiver mental health scores similar to those resulting from high motor function and low changes in memory and behavior in stroke survivors. Both stroke survivor characteristics and family functioning were associated with worse mental health of the caregiver, but not with the caregiver’s physical health. The mean for the PCS was similar and that for the MCS slightly lower than reported general norms (50th percentile) (Ware et al., 1994). During the stroke recovery period, the stress associated with rehabilitation may exacerbate problems within families that already are functioning poorly. Even in cases involving few stroke survivor memory and behavior changes, family conflict is associated with decrements in the mental health of caregivers. Some clinicians noted that many stroke survivors participated in the EXCITE clinical trial at the urging of the caregiver. The caregivers’ emotional investment of wanting the stroke survivor to participate in a therapy that could improve upper extremity function may contribute to family conflict surrounding stroke recovery. A randomized study found that a combination of education and counseling is effective for increasing stroke knowledge and reducing the decline in family TABLE 3. Summary of Hierarchical Regression Analysis for Variables Predicting Caregiver Mental Health (n ⫽ 128) Variable Step 1 Caregiver age Caregiver education Caregiver gender Relationship to stroke survivor Caregiver health problems General family functioning Step 2 SS motor function (SSMF) Memory & behavior changes (MBC) Family caregiver conflict (FCC) SSMF ⫻ MBC FCC ⫻ MBC Note. R2 ⫽ .13 for Step 1; ⌬R2 ⫽ .17 for Step 2 (p ⬍ .001). B SE B ␤ p Value .10 .50 .71 2.68 ⫺.26 ⫺5.64 .08 .76 1.94 2.53 1.80 2.08 .12 .05 .03 .099 ⫺.01 ⫺.26 .199 .510 .714 .292 .887 .008 .11 ⫺.42 ⫺.45 ⫺.01 .02 .07 .18 .13 .00 .01 .30 ⫺.40 ⫺.70 ⫺.58 .80 .119 .020 .001 .010 .004 Poststroke Influences on Caregivers’ Health 411 Nursing Research November/December 2004 Vol 53, No 6 TABLE 4. Summary of Hierarchical Regression Analysis for Variables Predicting Caregiver Physical Health (n ⫽ 128) SE B ␤ p Value ⫺.03 1.95 .82 ⫺.41 ⫺8.62 ⫺1.55 .06 .58 1.52 1.88 1.41 1.35 ⫺.04 .25 .04 ⫺.02 ⫺.48 ⫺.09 .920 .001 .556 .845 .000 .190 ⫺.16 ⫺.17 .05 .05 .09 .05 ⫺.51 ⫺.19 .09 .133 .807 .262 Variable Step 1 Caregiver age Caregiver education Caregiver gender Relationship to stroke survivor Caregiver health problems General family functioning Step 2 Stroke survivor motor function Memory and behavior changes Family caregiver conflict B Note. R2 ⫽ .34, p ⬍ .001 for Step 1; ⌬R2 ⫽ .02 for Step 2; ⌬R2 ⫽ NS. functioning (Evans, Matlock, Bishop, Stranahan, & Pederson, 1988). It is possible that the counseling reduced family conflict and improved the family’s ability to address stroke survivor memory and behavior changes. Caregivers within more effectively functioning family systems are more likely to receive emotional and tangible support. The caregiver’s perception that his or her family can work together to deal with difficult situations, which has been conceptualized as family hardiness (Clark, 2002), may allow caregivers to share the responsibility of caring for the stroke survivor and reduce their stress as caregivers. The specific inclusion criteria for participation in the constraint-induced therapy clinical trial required stroke survivors to demonstrate at least 10° of extension at the wrist and digits, 20° of extension at the elbow, and 45° of flexion at the shoulder. However, the average motor function of stroke survivors in this subacute recovery period was substantially slower than that reported in an earlier study of chronic stroke survivors (Wolf et al., 2001). Also, the frequency of memory and behavior changes among stroke survivors was substantially less than the midpoint of the scale, reflecting the relatively high functioning of stroke survivors in EXCITE. Therefore, stroke survivors’ range of physical ability was limited, and in a sample with a more representative range of function, the results may have been more conclusive. In this study, caregiver characteristics such as gender and relationship with care recipients were not associated with caregiver mental health outcomes. No psychological or family variables predicted the physical health of care- FIGURE 2. Interaction of stroke survivor’s (SS) motor function and memory and behavior (MB) changes with caregivers’ mental health. ⽧, Low SS Function; 䡲, Medium SS Function; 䊱, High SS Function. FIGURE 3. Interaction of family conflict and stroke survivor (SS) memory and behavior (MB) changes with caregivers’ mental health.⽧, Low SS MB; 䡲, High SS MB. 412 Poststroke Influences on Caregivers’ Health givers. Only education and a major health problem were associated with caregiver physical health. This may reflect the difference in measurement among studies. The PCS used in this study specifically reflects an individual’s ability to accomplish physical activities rather than a general selfrating of physical health. A limitation of this study is that the results cannot be generalized beyond White, well-educated female caregivers, caregivers of cognitively impaired stroke survivors (screened out if their Mini-Mental State Examination score is less than 24), and caregivers undergoing treatment for depression. Future studies should address these groups. Another limitation of the study is its cross-sectional design. It is difficult to separate current family functioning in response to a crisis from the historical functioning of the family. Although the findings indicate the importance of the family dynamics in the context of stroke recovery, these data cannot show whether this involves prestroke or poststroke functioning. The interaction of stroke survivors’ memory and behavior changes in motor function with caregivers’ mental health indicates that stroke survivors’ memory and behavior changes are the most salient for caregivers’ mental health because the combination of poor motor function and high memory and behavior changes has a significant negative effect. This illustrates the powerful nature of stroke survivors’ memory and behavior changes in their effect on caregivers’ mental health and the need for healthcare providers always to evaluate these as well as stroke survivor physical function. Addressing these changes will benefit stroke survivors as well. ▼ Accepted for publication July 4, 2004. This study was supported in part by the following grants: Family Function, Stroke Recovery, and Caregiver Outcomes (National Institute of Nursing Research, RO1 NR07612-01, to P.C.C.) and Extremity Constraint-Induced Therapy Evaluation (EXCITE) (National Center for Medical Rehabilitation Research [NICHHD] and NINDS, RO1 HD 37606, to S.L.W.). Participating EXCITE sites included Emory University, University of Southern California, University of North Carolina at Chapel Hill, Wake Forest University, Ohio State University, University of Florida-Gainesville, and Washington University School of Medicine—St. Louis, Missouri. Corresponding author: Patricia C. Clark, PhD, RN, FAHA, 1520 Clifton Road, Room 306, Emory University, Atlanta, GA 30322 (e-mail: pcclark@emory.edu). References Anderson, C. S., Linto, J., & Stewart-Wynne, E. G. (1995). A population-based assessment of the impact and burden of caregiving for long-term stroke survivors. Stroke, 26, 843-849. Bishop, D. S., & Evans, R. L. 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STATEMENT OF OWNERSHIP, MANAGEMENT, AND CIRCULATION (Act of August 12, 1970; Section 3685; Title 39 United States Code) Date of Filing—October 1, 2004. Title of Publication Nursing Research; Frequency of Issue— Bimonthly; Annual Subscription Price—$69.00; Location of Known Office of Publication—Lippincott Williams & Wilkins, Inc., 16522 Hunters Green Parkway, Hagerstown, MD 21740-2116; Location of the Headquarters or General Business Offices of the Publisher—Lippincott Williams & Wilkins, Inc., 530 Walnut Street, Philadelphia, PA 19106; Publisher—Lippincott Williams & Wilkins, Inc., 530 Walnut Street, Philadelphia, PA 19106; Editor—Molly C. Dougherty, PhD, RN, FAAN, School of Nursing, CB #7460, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7460. Managing Editor—Cynthia Wells, Lippincott Williams & Wilkins, 530 Walnut Street, Philadelphia, PA 19106; Owner—Lippincott Williams & Wilkins, Inc., 530 Walnut Street, Philadelphia, PA 19106, 351 West Camden Street, Baltimore, MD 21201; Wolters Kluwer, US, 333 Seventh Avenue, New York, NY 10001; Wolters Kluwer nv (owns 100% of stock), Stadouderskade 1, 1054 FS Amsterdam, The Netherlands; Known Bond Holders, Mortgagees, and other security holders owning or holding 1 percent or more of the total amount of bonds, mortgages, or other securities—None. A. Total no. of copies printed (net press run), average 6,475, actual 6,100. B. Paid and/or requested circulation 1. Paid/requested outside-county mail subscriptions stated on form 3541, average 3,754, actual 3,817; 2. Paid in-county subscriptions, none; 3. Sales through dealers and carriers, street vendors, counter sales, and other non-USPS paid distribution, average 1,220, actual 1,309; 4. Other classes mailed through the USPS, none. C. Total paid and/or requested circulation [sum of B (1), (2), (3), and (4)], average 4,974, actual 5,126. D. Free distribution by mail (samples, complimentary, and other free). Outside-county as stated on form 3541, average 153, actual 317; 2. In-county as stated on form 3541, none; 3. Other classes mailed through the USPS, none. E. Free distribution outside the mail (carriers or other means), average 20, actual 123. F. Total free distribution (sum of D and E), average 173, actual 440. G. Total distribution (sum of C and F), average 5,147, actual 5,566. H. Copies not distributed, average 1,328, actual 534. I. Total (sum of G and H), average 6,475, actual 6,100. Percent paid and/or requested circulation, average 96.64%, actual 92.09%. I certify that the statements made by me above are correct and complete. Jeffrey Brown, Manager, Periodicals Operations.