R eview Effects of Nurse-M anaged Protocols in the Outpatient M anagem ent of Adults W ith Chronic Conditions A Systematic Review and Meta-analysis Ryan J. Sh aw , P h D , RN; J e n n ife r R. M c D u ffie , PhD; C ris tin a C. H e n d rix , D N S , NP; A lis o n Edie, D N P , FNP; Linda L in d s e y -D a vis , P hD , RN; A v is h e k N a g i, M S ; A n d rzej S. K osinski, PhD; and John W . W illia m s Jr., M D , M H S c

Background: C hanges in fe d eral health p o licy are p ro v id in g m ore

fo llo w in g a p ro to co l. In a m eta-analysis, h e m o g lo b in A 1c level d e ­

access to m edical care fo r persons w ith c h ro n ic disease. P ro vid in g

creased b y 0 .4 %

q u a lity care m a y require a te a m appro ach, w h ic h th e A m erican

diastolic blo o d pressure decreased b y 3 .6 8 m m H g (Cl, 1 .0 5 to

C olle ge o f Physicians calls th e "m e d ic a l h o m e ." O n e n e w m od el

6.31

m a y in vo lv e n u rse-m a nag ed protocols.

Purpose: T o d e te rm in e w h e th e r nu rse-m a nag ed pro to co ls are e f­ fe c tiv e fo r o u tp a tie n t m a n a g e m e n t o f adults w ith diabetes, h y p e r­ ten sion , and h y p erlipidem ia.

mm

respectively

(9 5 % Cl, 0 .1 % to 0 .7 % ) (n = 8 ); systolic and

H g) and

1 .5 6 m m

H g (C l, 0 .3 6 to 2 .7 6 m m

(n = 12); to ta l cholesterol level decreased

Hg),

b y 0 .2 4

m m o l/L (9 .3 7 m g /d L ) (Cl, 0 .5 4 -m m o l/L decrease to 0 .0 5 -m m o l/L increase [2 0 .7 7 -m g /d L decrease to 2 .0 2 -m g /d L increase]) (n = 9); and

lo w -d e n s ity -lip o p ro te in

cholesterol level decreased

b y 0.31

m m o l/L (1 2 .0 7 m g /d L ) (C l, 0 .7 3 -m m o l/L decrease to 0 .1 1 -m m o l/L

Data Sources: MEDLINE, C ochra ne C entral R egister o f C o n tro lle d Trials, EMBASE, and CINAHL fro m January 1 9 8 0 th ro u g h January 2014.

increase [2 8 .2 7 -m g /d L decrease to 4 .1 3 -m g /d L increase]) (n = 6 ).

Limitation: Studies had lim ite d descriptions o f th e in te rve n tio n s and p ro to co ls used.

Study Selection: T w o review ers used e lig ib ility criteria to assess all titles, abstracts, and fu ll texts and resolved disagreem ents by dis­ cussion o r b y c o n s u ltin g a th ird review er.

Data Extraction: O n e re v ie w e r did d a ta abstractions and q u a lity assessments, w h ic h w e re c o n firm e d b y a second review er.

Data Synthesis: From 2 9 5 4 studies, 18 w e re in cluded. A ll studies used a registered nurse o r e q u iv a le n t w h o titra te d m edica tions by

Conclusion: A te a m ap pro ach th a t uses nurse-m a nag ed pro to cols m a y have po sitive effects on th e o u tp a tie n t m a n a g e m e n t o f adults w ith ch ro n ic co n d itio n s, h yp erlipidem ia.

such

as

diabetes,

hyp erten sion ,

and

Primary Funding Source: U.S. D e p a rtm e n t o f V eterans A ffairs. Ann Intern Med. 2014;161:113-121. doi:10.7326/M 13-2567

www.annals.org

For author affiliations, see end o f text.

edical management of chronic illness consumes 75% havioral health specialists. An organizing principle for care of every health care dollar spent in the United States teams is to utilize personnel at the highest level of their skill (1). Thus, provision of economical and accessible— yetset, which is particularly relevant given the expected in­ high-quality—care is a major concern. Diabetes mellitus, crease in demand for primary care services resulting from hypertension, and hyperlipidemia are prime examples of the Patient Protection and Affordable Care Act. chronic diseases that cause substantial morbidity and mor­ W ith this increased demand, the largest health care tality (2, 3) and require long-term medical management. workforce, registered nurses (RNs), may be a valuable asset For each of these disorders, most care occurs in outpatient alongside other nonphysician clinicians, including physi­ settings where well-established clinical practice guidelines cian assistants, nurse practitioners, and clinical pharma­ are available (4—7). Despite the availability of these guide­ cists, to serve more persons and improve chronic disease lines, there are important gaps between the care recom­ care. Robust evidence supports the effectiveness of nurses mended and the care delivered (8-10). The shortage of in providing patient education about chronic disease and primary care clinicians has been identified as 1 barrier to secondary prevention strategies (14-19). W ith clearly de­ the provision of comprehensive care for chronic disease fined protocols and training, nurses may also be able to (11, 12) and is an impetus to develop strategies for expand­ order relevant diagnostic tests, adjust routine medications, ing the roles and responsibilities of other interdisciplinary and appropriately refer patients. team members to help meet this increasing need. Our purpose was to synthesize the current literature The patient-centered medical home concept was de­ describing the effects of nurse-managed protocols, includveloped in an effort to serve more persons and improve chronic disease care. It is a model of primary care transfor­ mation that builds on other efforts, such as the chronic S ee a ls o : care model (13), and includes the following elements: E d ito ria l c o m m e n t ..................................................................... 153 patient-centered orientation toward the whole person, team-based care coordinated across the health care system W e b -O n ly and community, enhanced access to care, and a systemsS u p p le m e n ts based approach to quality and safety. Care teams may in­ C M E q u iz clude nurses, primary care providers, pharmacists, and be-

M

www.annals.org

15 July 2014 Annals of Internal Medicine IVolume 161 • Number 2 [ 1 1 3

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Figure 1.

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

S u m m a ry o f e v id e n c e se arch a n d s e le c tio n .

S e a rc h r e s u lts o f

E x c lu d e d a t t h e t i t l e / a b s t r a c t le v e l ( n = 2 6 1 5 )

re fe r e n c e s (n = 2 9 5 4 )

E x c lu d e d ( n = 3 1 9 ) N o t E n g lis h , w e s t e r n iz e d c o u n tr y , o r f u l l p u b li c a t io n : 5 5 R e tr ie v e d f o r

N o a d u l t s w i t h d is e a s e o f in t e r e s t

f u ll- t e x t re v ie w

o r c o n d u c t e d in a n o u t p a t i e n t

(n = 3 3 9 )

m e d ic a l s e t t i n g : 2 9 I n e l i g i b l e s t u d y d e s ig n o r c o m p a ra to r: 7 5 N o i n t e r v e n t io n o f in t e r e s t : 1 5 3 N o o u t c o m e o f in t e r e s t : 7

In c l u d e d ( n = 2 0 ) U n iq u e s tu d ie s : 1 8 C o m p a n io n a rtic le s : 2 *

* Methods or follow-up articles.

ing medication adjustment, for the outpatient manage­ ment of adults with common chronic conditions, namely diabetes, hypertension, and hyperlipidemia.

www.annals.org). Eligibility criteria included the involve­ ment of an RN or a licensed practical nurse (LPN) func­ tioning beyond the usual scope of practice, such as adjust­ ing medications and conducting interventions based on a written protocol. Potentially eligible articles were retrieved for further evaluation. Disagreements on inclusion or ex­ clusion were resolved by discussion or a third reviewer. Studies excluded at full-text review are listed in Supple­ ment 3 (available at www.annals.org). Abstraction and quality assessment were done by 1 reviewer and confirmed by a second. We piloted the abstraction forms, designed specifically for this review, on a sample of included articles. Key characteristics abstracted included patient descriptors, setting, features of the intervention and comparator, match between the sample and target populations, extent of the nurse interventionist’s training, outcomes, and quality ele­ ments. Supplements 4 and 5 (available at www.annals.org) summarize quality criteria and ratings, respectively. Because many studies were done outside the United States, we queried the authors of such studies about the education and scope of practice of the nurse intervention­ ists. Authors were e-mailed a table detailing the credentialing and scope of practice of various U.S. nurses and asked to classify their nurse interventionist. D a t a S y n t h e s is a n d A n a l y s i s

M

e th o d s

We followed a standard protocol for all steps of this review. A technical report that fully details our methods and presents results for all original research questions is available at www.hsrd.research.va.gov/publications/esp /reports.cfm. D a ta S o u rc e s a n d S e a rc h e s

In consultation with a master librarian, we searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, EMBASE, and CINAHL from 1 Janu­ ary 1980 through 31 January 2014 for English-language, peer-reviewed publications evaluating interventions that compared nurse-managed protocols with usual care in studies targeting adults with chronic conditions (Supple­ ment 1, available at www.annals.org). We selected exemplary articles and used a Medical Subject Heading analyzer to identify terms for “nurse pro­ tocols.” We added selected free-text terms and validated search terms for randomized, controlled trials (RCTs) and quasi-experimental studies, and we searched bibliographies of exemplary studies and applicable systematic reviews for missed publications (15, 17, 20-29). To assess for publi­ cation bias, we searched ClinicalTrials.gov to identify com­ pleted but unpublished studies meeting our eligibility criteria. S t u d y S e l e c t i o n , D a t a E x t r a c t io n , a n d Q u a l i t y Assessm ent

Two reviewers used prespecified eligibility criteria to assess all titles and abstracts (Supplement 2, available at 1 1 4 15 July 2014 Annals o f Internal Medicine Volume 161 • Number 2

The primary outcomes were the effects of nursemanaged protocols on biophysical markers (for example, glycosylated hemoglobin or hemoglobin Alc [HbAlc]), pa­ tient treatment adherence, nurse protocol adherence, adverse effects, and resource use. When quantitative syn­ thesis (that is, meta-analysis) was feasible, dichotomous outcomes were combined using odds ratios and continuous outcomes were combined using mean differences in random-effects models. For studies with unique but con­ ceptually similar outcomes, such as ordering a guidelineindicated laboratory test, we synthesized outcomes across conditions if intervention effects were sufficiently homoge­ neous. We used the Knapp and Hartung method (30, 31) to adjust the SEs of the estimated coefficients. For categories with several potential outcomes (for ex­ ample, biophysical markers) that may vary across chronic conditions, we selected outcomes for each chronic condi­ tion a priori: HbAlc level for diabetes, blood pressure (BP) for hypertension, and cholesterol level for hyperlipidemia. In 1 example (32), we imputed missing SDs using esti­ mates from similar studies. We computed summary estimates of effect and evalu­ ated statistical heterogeneity using the Cochran Q and I 2 statistics. We did subgroup analyses to examine potential sources of heterogeneity, including where the study was conducted and intervention content. Subgroup analyses in­ volved indirect comparisons and were subject to confound­ ing; thus, results were interpreted cautiously. Publication bias was assessed using a ClinicalTrials.gov search and funw w w .an n als.org

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

nel plots when at least 10 studies were included in the analysis. When quantitative synthesis was not feasible, we ana­ lyzed data qualitatively. We gave more weight to evidence from higher-quality studies with more precise estimates of effect. The qualitative syntheses identified and documented patterns in efficacy and safety of the intervention across conditions and outcome categories. We analyzed potential reasons for inconsistency in treatment effects across studies by evaluating variables, such as differences in study popu­ lation, intervention, comparator, and outcome definitions. We followed the approach recommended by the Agency for Healthcare Research and Quality (33) to eval­ uate the overall strength of the body of evidence. This approach assesses the following 4 domains: risk of bias, consistency, directness, and precision. These domains were considered qualitatively, and a summary rating of high, moderate, low, or insufficient evidence was assigned.

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Table. Study and Patient Characteristics of Included Diabetes, Hypertension, and Hyperlipidemia Studies

Characteristic

Cardiovascular Risk Studies, n ( % )

Total

Studies

18

Patients*

23 004

Design

RCT

16 (89)

Non-RCT

2 (1 1 )

Location

United States W estern Europe

7 (3 9 ) 11 (61)

Setting

General medical hospital Specialty hospital

12 (67) 3 (17)

Primary clinic and specialty hospital

2 (1 1 )

Telephone- and clinic-delivered care

1 (5.5)

R o le o f th e F u n d in g Source

The Veterans Affairs Quality Enhancement Research Initiative funded the research but did not participate in the conduct of the study or the decision to submit the manu­ script for publication.

Intervention

Target Glucose Blood pressure Lipids Delivery Clinic visits

R esults

Our electronic and manual searches identified 2954 unique citations (Figure 1). O f the 23 potentially eligible studies, 4 were excluded because we could not verify whether nurses had the authority to initiate or titrate med­ ications and the author did not respond to our query for clarification (34—37). We excluded a trial of older adults in which we could not differentiate the target illnesses (38). Approximately two thirds of the authors we contacted for missing data or clarification responded. We included 18 unique studies (23 004 patients) that focused on patients with elevated cardiovascular risk (Ta­ ble) (32, 39-55). O f these, 16 were RCTs and 2 were controlled before-and-after studies on diabetes (49, 53). The comparator was usual care in all but 1 study, in which a reverse-control design was used, and each intervention served as the control for the other. Eleven studies were done in Western Europe and 7 in the United States. Me­ dian age of participants was 58.3 years (range, 37.2 to 72.1 years) based on 16 studies. Approximately 47% of the par­ ticipants were female. Race was not reported in 84% of the studies. Supplement 5 gives detailed study characteristics. No outstanding studies were identified through ClinicalTrials.gov. Supplement 6 provides funnel plots that assess publication bias (available at www.annals.org). Overall, these studies displayed moderate risk of bias. Two studies were judged as having a high risk of bias because of inadequate randomization (44, 53), 12 were moderate risk (32, 3 9 -4 1 , 43, 47-52, 54), and 4 were low risk (42, 45, 46, 55). Other design issues affecting risk-ofbias ratings were possible contamination from a concurrent www.annals.org

Primarily telephone Duration 6 mo

15 (83) 11 (61) 9 (5 0 ) 15 (83) 3 (1 7 )

12 mo

2 (1 1 ) 8 (44.5)

>12 m ot

8 (44.5)

Nurse training

Specialist* Received study-specific training Case manager N ot described M ed ication initiation

3 (1 7 ) 10 (55) 1 (5.5) 4 (2 2 ) 11 (61)

Education or behavioral strategy

Education Specific behavioral stra te g y! Self-m anagem ent plan

1 6 (8 9 ) 3 (1 7 ) 9 (5 0 )

O utcom e

H em oglobin A 1c level Blood pressure Cholesterol level

12 (67) 14 (78)

Performance measure

1 5 (8 3 ) 13 (72)

Behavioral adherence Protocol adherence

4 (2 2 ) 1 (6)

Risk of b ias/q u ality

L ow /good M o de ra te /fair H ig h /p o or

4 (2 2 ) 12 (67) 2 (11)

RCT — randomized, controlled trial. * Number of patients represents the total mean of 22 839 and 23 170 because in 1 included study (30), hypertension and hyperlipidemia results were reported on 2 different but overlapping populations due to randomization, t Range, 14-36 mo. $ Clinical certification or diabetes nurse educator. § Motivational interviewing.

15 July 2014 Annals of Internal Medicine Volume 161 •Number 2 1 1 5

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F ig u r e 2 .

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

Effects of nurse-managed protocols on hemoglobin A1c level.

Study, Year (Reference)

Nurse Protocols Mean

A u b e rte ta l, 19 98 (4 0 )

7.10

Total, n

Mean

(SD) (1.33)

Usual Care

Total, n

(SD)

W eighted Mean Difference (95% Cl), %

51

8.20

-1 .1 0 (-1.62 t o -0 .5 8 )

8.35

-0 .1 5 (-0.33 to 0.03)

8.20

(1.74)

868

Houw eling et al, 2009 (47)

-1 .5 0

(1.35)

46

Houw eling et al, 2011 (46)

-0 .0 9

(1.07)

102

0.03

-0 .1 2 (-0.43 to 0.19)

M acMahon et al, 2009 (48)

-0 .3 4

(0.97)

94

0.12

-0 .4 6 (-0.74 t o -0 .1 8 )

O'H are et al, 2004 (52)

-0 .2 3

(1.42)

182

-0 .2 0

-0 .0 3 (-0.34 to 0.28) -0 .7 9 (-1 .2 4 t o -0 .34)

Bellary et al, 2 0 0 8 (4 2 )

Taylor et al, 2003 (32) W allymahmed et al, 2011 (54)

-0 .6 0 (-1.15 t o -0 .0 5 )

-0 .9 0

-1 .1 4

(1.35)

61

-0 .3 5

9.30

(1.40)

40

9.70

-0 .4 0 (-0 .9 9 to 0.19) -0 .4 0 (-0 .7 0 t o -0 .10)

Summary (/2 = 69.8% )

intervention, unblinded outcome assessors, and incomplete outcomes data. Characteristics o f the Interventions

All 18 study interventions used a protocol and re­ quired the nurse to titrate medications; however, only 11 reported that the nurse was independently allowed to ini­ tiate new medications. All but 1 study (55) provided the actual algorithm or citation. An RN (not an advanced practice RN) was the interventionist in all U.S. studies; a nurse with an equal scope of practice was the intervention­ ist in the non-U.S. studies. No studies reported use of LPNs. In 14 studies, interventions were delivered in a nurse-led clinic (3 9-42, 44, 46-54). Supervisors were nearly always physicians. O f the studies reporting nurses’ training, 3 used specialists (for example, diabetes-certified), 10 used RNs with study-specific training, and 1 used nurse case managers with experience in coordinating long-term care. Nurse protocols included additional components, such as education or self-management, in 16 studies. Two stud­ ies (41, 47) did not report additional intervention. Baseline characteristics showed that patients with diabetes had an elevated HbAlc level of approximately 8.0% or greater. Most patients with hypertension had moderate hyperten­ sion, and patients with hyperlipidemia had borderline high lipid levels. Outcomes were assessed at 6 to 36 months, with most studies reporting outcomes at 12 months or longer. Diabetes O utcom es

O f the 15 studies done in patients with diabetes, 10 RCTs (2633 patients) targeted glucose control. Figure 2 shows the forest plot of the random-effects meta-analysis on HbAlc level. Compared with usual care, nurse-managed protocols decreased HbAlc levels by 0.4% (95% Cl, 0.1% to 0 .7 %) (n = 8) and effects varied substantially (Q = 23.19; I 2 = 70%). In the 2 non-RCTs (49, 53) not in­ cluded in Figure 2, effects of the protocols on HbAlc level 1 1 6 15 July 2014 Annals of Internal Medicine Volume 161 • Number 2

were larger and in the same direction but had higher vari­ ability. Thus, nurse-managed protocols were associated with a highly variable mean decrease in HbAlc level. Other diabetes-related performance measures were rarely reported (Supplement 6). In 1 controlled beforeand-after study (53), achieving target eye examination, uri­ nary microalbumin-creatinine ratio, and foot examination goals was reported to reach 80% to 100% using nursemanaged protocols. A second study (49) found a nonsig­ nificant increase in intervention patients achieving eye and foot examination goals compared with control participants. Reduction in the proportion of patients with an HbAlc level of 8 .5% or greater was achieved in 1 study (odds ratio, 1.69 [Cl, 1.25 to 2.29]) (49). BP O utcom es

Fourteen studies reported BP outcomes: 13 RCTs (10 362 patients) and 1 non-RCT (885 patients). Re­ stricted to the 12 RCTs specifically addressing BP (10 224 patients), the intervention decreased systolic BP by 3.68 mm Hg (Cl, 1.05 to —6.31 mm Hg) and diastolic BP by 1.56 mm Hg (Cl, 0.36 to 2.76 mm Hg), with high vari­ ability (72 > 70%) (Figures 3 and 4). Funnel plots sug­ gested possible publication bias with systolic but not dia­ stolic BP (Supplement 6). Overall, nurse-managed protocols were associated with a mean decrease in systolic and diastolic BP. Eleven of the 18 studies focused on achieving various target BPs: 10 RCTs (9707 patients) and 1 non-RCT (885 patients). When the analysis was restricted to RCTs, nursemanaged protocols were more likely to achieve target BP than control protocols (odds ratio, 1.41 [Cl, 0.98 to 2 .02]), but these results could have been due to chance, and treatment effects were highly variable (Q = 35 .20 ; / 2 = 74 %) (Supplement 7, available at www.annals.org). Using the summary odds ratio and median event rate from the control group of the trials that implemented nurse pro­ tocols, we estimated the absolute treatment effect as a risk w w w . a n n a ls .o r g

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

difference of 120 more patients achieving target total BP per 1000 patients (Cl, 6 fewer to 244 more). Funnel plots suggested some asymmetry but no clear publication bias.

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mmol/L (12.07 mg/dL) (Cl, 0.73-mmol/L decrease to 0.11-mmol/L increase [28.27-mg/dL decrease to 4.13mg/dL increase]) (n = 6), with marked variability in inter­ vention effects (72 > 89%) (Figure 4). Effects of nursemanaged protocols on total and low-density lipoprotein cholesterol levels from the 2 non-RCTs (49, 53) were in the same direction. Reductions in total cholesterol level were not statistically significant. Overall, nurse-managed protocols were associated with a mean decrease in total and low-density lipoprotein cholesterol levels. All 11 studies (9221 patients) targeting various total cholesterol levels were included in the quantitative analysis (Supplement 7). Nurse-managed protocols were statisti­ cally significantly more likely to achieve target total choles­ terol levels than control protocols (odds ratio, 1.54 [Cl,

H y p e r lip id e m ia O u t c o m e s

Fifteen studies reported hyperlipidemia outcomes: 13 RCTs (14 817 patients) and 2 non-RCTs (1114 patients). O f these, 9 RCTs (3494 patients) specifically addressed total cholesterol levels and 6 RCTs specifically addressed low-density lipoprotein levels (1095 patients). In analyses restricted to these trials, the intervention was associated with a decrease in total cholesterol level. Total cholesterol levels decreased by 0.24 mmol/L (9.37 mg/dL) (Cl, 0.54mmol/L decrease to 0.05-mmol/L increase [20.77-mg/dL decrease to 2.02-mg/dL increase]) [n = 9), and lowdensity lipoprotein cholesterol levels decreased by 0.31

Figure 3. Effects o f nurse-m an ag ed protocols on systolic (top) and d ia sto lic ( b o tto m ) blood pressure. Study, Year (Reference)

Nurse Protocols Mean

Total, n

(SD)

Usual Care Mean

Total, n

Weighted Mean Difference (95% Cl), mm Hg

(SD)

Bebb et al, 2007 (41)

143.30

(19.50)

743

143.10

(17.70)

677

0.20 (-1.73 to 2.13)

Bellary et al, 2008 (42)

134.30

(20.36)

868

134.60

(20.36)

618

-0.30 (-2.40 to 1.80)

Denver et al, 2003 (44)

-9.90 (-17.46 t o -2.34)

141.10

(19.30)

59

151.00

(21.90)

56

Houweling et al, 2009 (47)

-8.60

(20.54)

46

-4.00

(14.91)

38

-4.60 (-12.20 to 3.00)

Houweling et al, 2011 (46)

-7.40

(17.82)

102

-5.60

(16.45)

104

-1.80 (-6.49 to 2.89)

MacMahon et al, 2009 (48)

-10.50

(17.45)

94

1.70

(19.39)

94

-12.20 (-17.47 t o -6.93)

New et al, 2003 (51)

147.00

(20.23)

506

149.00

(20.23)

508

-2.00 (-4.49 to 0.49)

New et al, 2004 (50)

142.00

(24.00)

2474 142.17

(24.00)

2531

-0.17 (-1.50 to 1.16)

-6.69

(21.24)

182

-2.11

(17.47)

179

-4.58 (-8.59 to -0,57)

-14.20

(16.23)

69

-5.70

(18.59)

68

-8.50 (-14.35 t o -2.65)

4.40

(17.45)

61

8.60

(19.39)

66

-4.20 (-10.61 to 2.21)

115.00

(13.00)

40

124.00

(14.00)

41

-9.00 (-14.88 t o -3.12)

O'Hare et al, 2004 (52) Rudd et al, 2004 (55) Taylor et al, 2003 (32) Wallymahmed et al, 2011 (54) Summary (/2 = 75.1%)

-3.68 (-6.31 t o -1.05) -2 0

I

“1

-15

-1 0

-5

0

Weighted Mean Difference, mm Hg

Study, Year (Reference)

Nurse Protocols

Total, n

Usual Care

Mean

(SD)

Bebb et al, 2007 (41)

78.20

(10.20)

Bellary et al, 2008 (42)

78.40

(8.63)

Denver et al, 2003 (44)

79.90

(10.60)

59

82.20

Houweling et al, 2009 (47)

-1.40

(9.09)

46

-2.40

Houweling et al, 2011 (46)

-3.20

(10.18)

102

-1.00

(9.26)

MacMahon et al, 2009 (48)

-5.90

(8.72)

94

-0.51

New et al, 2003 (51)

74.00

(11.29)

506

74.79

New et al, 2004 (50)

78.20

(16.06)

2474

O'Hare et al, 2004 (52)

-3.14

(10.56)

Rudd et al, 2004 (55)

-6.50

Taylor et al, 2003 (32)

2.20

(9.00)

Wallymahmed et al, 2011 (54)

65.00

Total, n

Weighted Mean Difference (95% Cl), mm Hg

Mean

(SD)

743

77.90

(10.40)

677

0.30 (-0.77 to 1.37)

868

80.31

(8.63)

618

-1.91 (-2.80 t o -1.02)

(12.40)

56

-2.30 (-6.53 to 1.93)

(7.61)

38

1.00 (-2.57 to 4.57)

104

-2.20 (-4.86 to 0.46)

(9.69)

94

-5.39 (-8.03 to -2.75)

(11.29)

508

-0.79 (-2.18 to 0.60)

78.11

(16.06)

2531

0.09 (-0.80 to 0.98)

182

0.28

(10.00)

179

-3.42 (-5.54 t o -1.30)

(10.00)

69

-3.40

(7.90)

68

-3.10 (-6.12 t o -0.08)

(10.00)

61

1.90

(9.30)

66

0.30 (-3.07 to 3.67)

40

69.00

(9.00)

41

-4.00 (-7.92 to -0.08)

Summary (/2 = 75.1 %)

-1.56 (-2.76 t o -0.36)

I---------------- 1-----------------1 0

-5

0

Weighted Mean Difference, mm Hg

w w w .an n als.org

15 July 2014 Annals of Internal Medicine Volume 161 • Number 2 1 1 7

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Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

F igure 4. E ffe c ts o f n u r s e -m a n a g e d p ro to c o ls o n to ta l c h o le s te ro l ( t o p ) a n d lo w - d e n s it y lip o p r o te in c h o le s te ro l ( b o t t o m ) le v e ls .

Study, Year (Reference)

Nurse Protocols Total, n

Usual Care Mean

Mean (SD)

Total, n

Weighted Mean Difference (95% Cl), mg/dL

(SD)

Allison etal, 1999 (39)

-19.00

(35.00)

80

-16.00

(35.00)

72

Bellary et al, 2008 (42)

181.50

(26.08)

868

180.35

(26.08)

618

DeBusk etal, 1994 (43)

184.55

(32.05)

243

208.88

(40.54)

244

-3.00 (-14.14 to 8.14) 1.15 (-1.54 to 3.84) -24.33 (-30.82 to -17.84)

Houweling et al, 2009 (47)

-15.44

(26.00)

46

-34.74

(46.94)

38

Houweling et al, 2011 (46)

-3.86

(39.30)

102

-1.93

(29.77)

104

MacMahon et al, 2009 (48)

-26.64

(37.45)

94

-6.17

(37.45)

94

New etal, 2003 (51)

189.20

(41.20)

345

200.01

(41.20)

338

Taylor et al, 2003 (32)

-20.60

(26.00)

61

-11.50

(29.00)

66

Wallymahmed et al, 2011 (54)

166.00

(38.60)

40

200.80

(38.60)

41

19.30 (2.59 to 36.01) -1.93 (-11.47 to 7.61) -20.47 (-31.18 to -9.76) -10.81 (-16.99 to -4.63) -9.10 (-18.67 to 0.47) -34.80 (-51.61 to -17.99)

Summary U2 = 90.8%)

-9.37 (-20.77 to 2.02)

----- 1-----4 0

-2 0

0

20

Weighted Mean Difference, mg/dL

Study, Year (Reference)

Nurse Protocols Total, n Mean

(SD)

Usual Care Mean

Total, n

Allison et al, 1999 (39)

-21.00

(31.00)

80

-23.00

(30.00)

72

DeBusk etal, 1994 (43)

106.95

(26.64)

243

131.66

(34.75)

244

Houweling et al, 2009 (47)

-11.58

(26.03)

46

-23.17

(30.51)

38

MacMahon et al, 2009 (48)

-20.85

(37.45)

94

-0.39

(37.45)

94

Taylor etal, 2003 (32)

-19.40

(31.00)

61

-6.50

(30.00)

66

84.94

(30.89)

40

111.97

(30.89)

41

Wallymahmed et al, 2011 (54)

Weighted Mean Difference (95% Cl), mg/dL

(SD) I

■

2.00 (-7.70 to 11.70)

•

-24.71 (-30.21 to -19.21) 11.59 (-0.69 to 23.87)

I------------ ■-------- 1

-20.46 (-31.17 t o -9.75)

I--------■—

-12.90 (-23.53 to -2.27)

I- -------- ■---------- 1

-27.03 (-40.49 to -13.57)

Summary (I2 = 89.1%)

-12.07 (-28.27 to 4.13) -4 5

-2 5

0

25

Weighted Mean Difference, mg/dL

To convert mg/dL to mmol/L, multiply by 0.0259.

1.02 to 2.31]), with substantial variability in treatment effects (Q = 71.59; / 2 = 86%). Using the summary odds ratio and median event rate from the control group of the RCTs, we estimated the absolute treatment effect as a risk difference of 106 more patients achieving target total cho­ lesterol levels per 1000 patients (Cl, 5 to 196). Funnel plots did not suggest publication bias (Supplement 6). P a tie n t A d h e re n c e to T re a tm e n t

Behavioral adherence was reported in 4 studies (39, 43, 48, 49). In 1 study, the rate of daily medication adher­ ence (±SE) for the intervention group during the 6-month study was 80.5% ± 23.0% compared with 69.2% ± 31.1% for the usual care group (P = 0.03) (55). When reported, effects on lifestyle changes and medication adher­ ence showed an overall pattern of small positive effects associated with nurse-managed protocols. A d h e re n c e to P rotocols

Two studies (39, 52) reported data on nurses’ adher­ ence to treatment protocols. When compared with usual care, nurses instituted pharmacologic therapy for lipid management more often (39). O ’Hare and colleagues (52) found that hypoglycemic agents and antihypertensives, in1 1 8 15 July 2014 Annals of Internal Medicine Volume 161 • Number 2

eluding angiotensin-converting enzyme inhibitors, angio­ tensin II antagonists, and statins, were started or doses were increased by nurses following treatment protocols more of­ ten than in usual care groups. A dverse Effects

The included studies had few reports on adverse effects associated with nurse-managed protocols. Only 1 study on diabetes in a U.S. H M O (40) reported adverse effects. Severe low blood glucose events were identical (1.5%) at baseline and increased similarly— 2.9% in the control group compared with 3.1% in the intervention group (P = 0.158). Resource Use

Resource use was reported in only 3 studies (45, 47, 51). Houweling and colleagues (47) found total salary costs (±SE) to be significantly lower in the intervention group (€114.6 ± €50.4) than in the control group (€138.3 ± €48.3; P < 0.001). In this same study, total costs for med­ ication were reported to be lower in the intervention groups (€136.3 ± €91.9) than in the control group (€149.0 ± €94.4; P > 0.05) at study completion. www.annals.org

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

Inpatient costs were reported to be substantially lower in 2 other studies. One study (45) estimated total inpatient costs for the intervention group at $869 535 compared with $1 702 682 for the control group (P = 0.02). The second study (51) reported decreases in costs by sex, with the intervention groups achieving a decrease of $606 for men and $888 for women. Further, total outpatient costs were reported at $1 237 270 in the nurse-managed proto­ col group compared with $1 381 900 in the control group ( P = 0.47) (51). S u b g ro u p A n aly sis

We did subgroup analyses comparing studies that were conducted in the United States compared with other coun­ tries, had targeted HbAlc alone compared with multiple conditions, and incorporated self-management plans com­ pared with those that did not. These analyses showed greater effects on decreasing HbAlc level only for studies done on diabetes management in the United States (—0.92 vs. —0.23; P — 0.01). Treatment variability was reduced in these subgroups. Therefore, some variability in diabetes care may be explained by country or specificity of the in­ tervention. For BP and cholesterol, subgroup analysis found no statistically significant differences in treatment effects. We planned to conduct subgroup analyses examin­ ing the intervention primarily by clinic visits compared with telephone calls, but variability in the results was insufficient. D

is c u s s io n

Nurse-managed protocols in the studies we examined had a consistently positive effect on chronically ill patients. Hemoglobin A lc levels decreased by approximately 0.4% (moderate strength of evidence [SOE]). Systolic and dia­ stolic BP decreased by 4 mm Hg and 2 mm Hg, respec­ tively (moderate SOE). Total cholesterol levels decreased by 0.24 mmol/L (9.37 mg/dL), and low-density lipopro­ tein cholesterol levels decreased by 0.31 mmol/L (12.07 mg/dL) (low SOE). Important differences were found in treatment effects across studies for most outcomes. Sub­ group analyses explained little of this variability and showed differences only for effects on HbAlc level between non—U.S.-based and U.S.-based studies. Effects of nursemanaged protocols on lifestyle changes and medication ad­ herence were reported infrequently, but when reported, they showed an overall pattern of small positive effects (low SOE). The SOE was insufficient to estimate a treatment ef­ fect for all other outcomes: protocol adherence, adverse effects, and resource use. Indirect evidence (for example, proportion of patients prescribed the indicated medication) suggests reasonable adherence to the protocol by nurses. Although these studies showed protocol adherence by nurses in intervention groups compared with control par­ ticipants, the SOE on nurse adherence was judged to be insufficient. Further, only 1 of the 18 studies reported adw w w . a n n a ls .o r g

R

e v ie w

verse effects (40); therefore, the SOE was judged to be insufficient to determine the effect of nurse-managed pro­ tocols on adverse effects in treatment studies about chronic disease. Finally, resource use was reported in only 3 studies (45, 47, 51), so the evidence is insufficient to determine any effect. Our study has many strengths, including a protocoldriven review, a comprehensive search, careful quality as­ sessment, and rigorous quantitative synthesis methods. However, our report and the literature also have limita­ tions. Because inclusion criteria required medication titra­ tion, we may have missed studies in which nurses had autonomy to practice in other capacities beyond their scope of practice. We did not include studies of inpatient settings in which nurses might often use protocols. The literature lacked detailed descriptions of the interventions and protocols used. Studies had limited descriptions of in­ tervention intensity; treatment adherence; nurses’ educa­ tion levels, training, or supervision; protocol adherence; adverse effects; and resource use. Eleven of the 18 studies were done in countries outside the United States, which may limit applicability to U.S practices. Other perfor­ mance measures were rarely reported. Studies were limited to the use of RNs; there was no report of using LPNs. Finally, the reported outcomes varied across studies and contributed to unexplained variability. With changes in federal health policy, new models are needed to provide more accessible and effective chronic disease care. The implementation of a patient-centered medical home model will play a critical role in reconfigur­ ing team-based care and will expand the responsibilities of team members. Our review shows that team approaches using nurse-managed protocols help improve health out­ comes among patients with moderately severe diabetes, hy­ pertension, and hyperlipidemia. In addition, RNs can suc­ cessfully titrate medications according to protocols for these conditions. Similar results were found on the effects of quality improvement strategies on glycemic control in type 2 diabetes where case managers did not have to wait for physician approval to adjust medications (56). Further research is needed to understand the effects of nursemanaged protocols in caring for complex or unstable pa­ tients. Supplement 8 (available at www.annals.org) pres­ ents a detailed table of identified evidence gaps and a framework for future research. As the largest health care workforce group, nurses are in an ideal position to collaborate with other team mem­ bers in the delivery of more accessible and effective chronic disease care. Team members, such as clinical pharmacists, may also be able to serve in similar capacities and in areas with limited health care resources (57). Thus, health care systems will need to balance the benefits and costs associ­ ated with each team member and determine who is best suited to take on these expanded roles. Results from our review suggest that nurse-managed protocols have positive 15 July 2014 Annals of Internal Medicine Volume 161 • Number 2 1 1 9

Review

Nurse-Managed Protocols in Managing Outpatients With Chronic Conditions

effects on outpatient care of adults with chronic conditions. F rom D u rh am Veterans Affairs C enter for H ealth Services Research in Prim ary Care; G eriatric Research, E ducation, and Clinical C enter, D u r­ h am Veterans Affairs M edical C enter; and D uke U niversity, D urham , N o rth Carolina. D isclaim er: T h e co n ten t is solely the responsibility o f the authors and

does n o t necessarily represent the official views o f U.S. D epartm ent o f Veterans Affairs or D uke U niversity. Ail w ork herein is original. All authors m eet the criteria for authorship, including acceptance o f respon­ sibility for the scientific content o f the m anuscript. A c k n o w le d g m e n t: T h e authors thank C onnie Schardt, MLS, for help

w ith the literature search and retrieval and Liz W ing, M A, for editorial assistance. Financial Support: T his report is based on research conducted by the

Evidence-based Synthesis Program (ESP) C enter located at the D urham Veterans Affairs M edical C enter, D urham , N o rth C arolina, w hich is funded by the D ep artm en t o f Veterans Affairs, Veterans H ealth A dm in­ istration, Office o f Research and D evelopm ent, H ealth Services Research and D evelopm ent (VA-ESP Project 09-010; 2013). T h e first author, Dr. Ryan Shaw, was supported by a D epartm ent o f Veterans Affairs H ealth Services Research and D evelopm ent Office o f A cademic Affiliations nursing postdoctoral research award (T P P -21-021). Disclosures: D r. W illiam s reports grants from Veterans Affairs H ealth

Services Research and D evelopm ent during the conduct o f the study. A uthors n o t nam ed here have disclosed no conflicts o f interest. Disclosures can be viewed at w w w .acponline.org/authors/icm je/C onflict O fln terestF o tm s.d o ?m sN u m = M 13-2567. Requests fo r S ingle Reprints: Ryan J. Shaw, P hD , R N , H ealth Services

Research and D evelopm ent (152), 411 W est C hapel H ill Street, Suite 600, D u rh am , N C 27701; e-mail, ryan.shaw@ duke.edu. C u rren t au th o r addresses and author contributions are available at ww w .annals.org.

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w w w .a n n a ls .o rg

R eview

44. Denver EA, Barnard M, Woolfson RG, Earle KA, Management of uncon­ trolled hypertension in a nurse-led clinic compared with conventional care for patients with type 2 diabetes. Diabetes Care. 2003;26:2256-60. [PMID: 12882845] 45. Fischer H H , Eisert SL, Everhart RM, Durfee MJ, Moore SL, Soria S, et al. Nurse-run, telephone-based outreach to improve lipids in people with diabetes. Am J Manag Care. 2012;18:77-84. [PMID: 22435835] 46. Houweling ST, Kleefstra N, van Hateren IQ, Groenier KH, Meyboom-de Jong B, Bilo HJ. Can diabetes management be safely transferred to practice nurses in a primary care setting? A randomised controlled trial. J Clin Nurs. 2011;20:1264-72. [PMID: 21401764] 47. Houweling ST, Kleefstra N, van Hateren KJ, Kooy A, Groenier KH, Ten Vergert E, et al; Langerhans Medical Research Group. Diabetes specialist nurse as main care provider for patients with type 2 diabetes. Neth J Med. 2009;67: 279-84. [PMID: 19687522] 48. MacMahon Tone J, Agha A, Sherlock M, Finucane F, Tormey W , Thom p­ son CJ. An intensive nurse-led, multi-interventional clinic is more successful in achieving vascular risk reduction targets than standard diabetes care. Ir J Med Sci. 2009;178:179-86. [PMID: 19367427] 49. Meulepas MA, Braspenning JC, de Grauw WJ, Lucas AE, Wijkel D, Grol RP. Patient-oriented intervention in addition to centrally organised checkups improves diabetic patient outcome in primary care. Qual Saf Health Care. 2008; 17:324-8. [PMID: 18842969] 50. New JP, Mason JM , Freemantle N, Teasdale S, W ong L, Bruce NJ, et al. Educational outreach in diabetes to encourage practice nurses to use primary care hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled trial. D iabetM ed. 2004;21:599-603. [PMID: 15154946] 51. N ew JP, Mason JM , Freemantle N, Teasdale S, W ongL M , Bruce NJ, et al. Specialist nurse-led intervention to treat and control hypertension and hyperlip­ idemia in diabetes (SPLINT): a randomized controlled trial. Diabetes Care. 2003;26:2250-5. [PMID: 12882844] 52. O ’Hare JP, Raymond N T , Mughal S, Dodd L, H anif W , Ahmad Y, et al; UKADS Study Group. Evaluation of delivery of enhanced diabetes care to pa­ tients of South Asian ethnicity: the United Kingdom Asian Diabetes Study (UKADS). Diabet Med. 2004;21:1357-65. [PMID: 15569141] 53. Philis-Tsimikas A, Walker C, Rivard L, Talavera G, Reimann JO, Salmon M, et al; Project D uke. Improvement in diabetes care of underinsured patients enrolled in project dulce: a community-based, culturally appropriate, nurse case management and peer education diabetes care model. Diabetes Care. 2004;27: 110-5. [PMID: 14693975] 54. Wallymahmed ME, Morgan C, Gill GV, Macfarlane LA. Nurse-led cardio­ vascular risk factor intervention leads to improvements in cardiovascular risk tar­ gets and glycaemic control in people with Type 1 diabetes when compared with routine diabetes clinic attendance. Diabet Med. 2011;28:373-9. [PMID: 21204963] 55. Rudd P, Miller N H , Kaufman J, Kraemer HC, Bandura A, Greenwald G, et al. Nurse management for hypertension. A systems approach. Am J Hypertens. 2004;17:921-7. [PMID: 15485755] 56. Shojania KG, Ranji SR, McDonald KM, Grimshaw JM, Sundaram V, RushakoffRJ, et al. Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis. JAMA. 2006;296:427-40. [PMID: 16868301] 57. Martinez AS, Saef J, Paszczuk A, Bhatt-Chugani H. Implementation of a pharmacist-managed heart failure medication titration clinic. Am J Health Syst Pharm. 2013;70:1070-6. [PMID: 23719886]

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