Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 Complementary Therapies in Medicine (2014) xxx, xxx—xxx Available online at www.sciencedirect.com ScienceDirect j o u r n a l h o m e p a g e : w w w . e l s e v i e r h e a l t h . c o m / j o u r n a l s / c t i m Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials� Hiroharu Kamioka a,∗, Shinpei Okada b, Kiichiro Tsutani c, Hyuntae Park d, Hiroyasu Okuizumi e, Shuichi Handa e, Takuya Oshio f, Sang-Jun Park b, Jun Kitayuguchi g, Takafumi Abe g, Takuya Honda h, Yoshiteru Mutoh i a Faculty of Regional Environment Science, Tokyo University of Agriculture, Japan b Physical Education and Medicine Research Foundation, Japan c Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan d Department of Functioning Activation, National Center for Geriatrics and Gerontology, Japan e Mimaki Onsen (Spa) Clinic, Tomi City, Japan f Social Welfare Service Corporation CARE-PORT MIMAKI, Japan g Physical Education and Medicine Research Center Unnan, Japan h Japanese Society for the Promotion of Science, Japan i The Research Institute of Nippon Sport Science University, Japan KEYWORDS Animal-assisted therapy; Systematic review; Randomized controlled trials Summary The objectives of this review were to summarize the evidence from randomized controlled trials (RCTs) on the effects of animal-assisted therapy (AAT). Studies were eligible if they were RCTs. Studies included one treatment group in which AAT was applied. We searched the following databases from 1990 up to October 31, 2012: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi Web, GHL, WPRIM, and PsycINFO. We also searched all Cochrane Database up to October 31, 2012. Eleven RCTs were identified, and seven studies were about ‘‘Mental and Please cite this article in press as: Kamioka H, et al. Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials. Complement Ther Med (2014), http://dx.doi.org/10.1016/j.ctim.2013.12.016 behavioral disorders’’. Types of animal intervention were dog, cat, dolphin, bird, cow, rabbit, ferret, and guinea pig. The RCTs conducted have been of relatively low quality. We could not perform meta-analysis because of heterogeneity. In a study environment limited to the people who like animals, AAT may be an effective treat- ment for mental and behavioral disorders such as depression, schizophrenia, and alcohol/drug addictions, and is based on a holistic approach through interaction with animals in nature. � This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. ∗ Corresponding author at: Faculty of Regional Environment Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Tel.: +81 3 5477 2587; fax: +81 3 5477 2587. E-mail address: h1kamiok@nodai.ac.jp (H. Kamioka). 0965-2299/$ — see front matter © 2014 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ctim.2013.12.016 dx.doi.org/10.1016/j.ctim.2013.12.016 dx.doi.org/10.1016/j.ctim.2013.12.016 http://www.sciencedirect.com/science/journal/09652299 www.elsevierhealth.com/journals/ctim mailto:h1kamiok@nodai.ac.jp dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN+ModelYCTIM-1299; No. of Pages 20 2 To most effectively assess the pot to utilize and describe (1) RCT me (3) intervention dose, (4) adverse © 2014 The Authors. Published by C I A a t h h ontents Introduction ............................................................................................................... 00 Methods ................................................................................................................... 00 Criteria for considering studies included in this review ............................................................... 00 Types of studies................................................................................................ 00 Types of participants........................................................................................... 00 Types of intervention and language ............................................................................ 00 Types of outcome measures .................................................................................... 00 Search methods for identification of studies .......................................................................... 00 Bibliographic database......................................................................................... 00 Search strategies .............................................................................................. 00 Registry checking .............................................................................................. 00 Handsearching, reference checking, and other................................................................. 00 Review methods ...................................................................................................... 00 Selection of trials .............................................................................................. 00 Risk of bias (quality) assessment ............................................................................... 00 Summary of studies and data extraction ....................................................................... 00 Benefit, harm, and cost ........................................................................................ 00 Analysis ........................................................................................................ 00 Research protocol registration ................................................................................. 00 Results .................................................................................................................... 00 Study selection ....................................................................................................... 00 Study characteristics ................................................................................................. 00 Quality assessment ................................................................................................... 00 Meta-analysis ......................................................................................................... 00 Adverse events ....................................................................................................... 00 Costs of intervention ................................................................................................. 00 Discussion ................................................................................................................. 00 Tendency of target disease and outcome ............................................................................. 00 Validity of overall evidence based on quality assessment ............................................................. 00 Overall evidence and quality assessment....................................................................... 00 Overall evidence............................................................................................... 00 Future research agenda to build evidence ..................................................................... 00 Strength and limitations ....................................................................................... 00 Conclusion ................................................................................................................ 00 Contributors............................................................................................................... 00 Funding ................................................................................................................... 00 Conflict of interest statement ............................................................................................. 00 Ethical approval ........................................................................................................... 00 Data sharing............................................................................................................... 00 Acknowledgements ........................................................................................................ 00 Appendix. References to studies excluded in this review ................................................................ 00 References ................................................................................................................ 00 ntroduction nimals have been our companions since ancient times, animals as tools for improving physical, mental and social functions, and educational and welfare aspects of humans are called animal-assisted interventions (AAI). Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h nd we are well aware of the many ways that some of hem have aided us throughout history.1 Animals are used to elp humans in ways; for example, serving as working shire orses and guide dogs for the blind.2 The modalities that use s t A PRESS H. Kamioka et al. ential benefits for AAT, it will be important for further research thodology when appropriate, (2) reasons for non-participation, effects and withdrawals, and (5) cost. Elsevier Ltd. All rights reserved. To understand the different types of AAI and integrate eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 ome useful definitions, we accepted the classification of he American Veterinary Medical Association (AVMA).3 The VMA classifies AAI into three category: (i) animal-assisted dx.doi.org/10.1016/j.ctim.2013.12.016 IN+Model N C b O s i o S T t W ( u l r i R W f S i N 3 c u t C p a d H W j s R S I a T t u ( ( w p a p R I a ARTICLEYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy activities (AAA) that utilize companion animals, (ii) animal assisted-therapy (AAT) that utilizes therapy animals, and (iii) service animal programs (SAP) that utilize service animal. Especially, AAT is a goal-directed intervention in which an animal that meets specific criteria is an integral part of the treatment process. These programs are usually directed and delivered by human health or human services professionals with specialized expertise and within the scope of practice of their profession. A pioneer systematic review (SR) of AAT showed that overall it was associated with moderate effects in improv- ing outcomes in four areas: autism-spectrum symptoms, medical difficulties, behavioral problems, and emotional well-being.4 However, contrary to expectations, character- istics of the SR participants and studies did not produce differential outcomes. Some limitations of the SR were that it only included articles published prior to 2004, and it did not include randomized controlled trials (RCTs). It is well known in research design that evidence grading is highest for a SR with meta-analysis of RCTs. Although many studies have reported the effects of AAT,1,4,5 there is no SR of the evidence based on RCTs. Therefore, the objective of this review was to summarize the evidence from RCTs on the effects of AAT. Methods Criteria for considering studies included in this review Types of studies Studies were eligible if they were RCTs. Types of participants There was no restriction on participants. Types of intervention and language Studies included at least one treatment group in which AAT was applied. The definition of AAT in this study was based on the classification of the AVMA.3 Type of animal was not a restriction but we excluded robotic animals (e.g., robotic dog). There was no restriction on the basis of language. Types of outcome measures We focused on all cure and rehabilitation effects using the International Classification of Diseases-10 (ICD-10). Search methods for identification of studies Bibliographic database We searched the following databases from 1990 up to October 31, 2012: MEDLINE via PubMed, CINAHL, Web of Sci- ence, Ichushi Web (in Japanese), the Global Health Library (GHL), the Western Pacific Region Index Medicus (WPRIM), and PsycINFO. We also searched the Cochrane Database of Systematic Reviews (Cochrane Reviews), the Database of Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h Abstracts of Reviews of Effects (DARE), the Cochrane Cen- tral Register of Controlled Trials (CENTRAL), the Cochrane Methodology Register (Methods Studies), the Health Tech- nology Assessment Database (Technology Assessments), the a i m c PRESS 3 HS Economic Evaluation Database (NHS EED), The Cochrane ollaboration databases (Cochrane Groups), and the Camp- ell Systematic Reviews (the Campbell Collaboration) up to ctober 31, 2012. All searches were performed by a specific earcher (hospital librarian) who was qualified in medical nformation handling, and who was sophisticated in searches f clinical trials. earch strategies he special search strategies contained the elements and erms for MEDLINE, CINAHL, Web of Science, Ichushi eb, GHL, WPRIM, PsycINFO, and All Cochrane databases Table 1). Only keywords relating to the intervention were sed for the searches. Titles and abstracts of identified pub- ished articles were reviewed in order to determine the elevance of the articles. References in relevant studies and dentified RCTs were screened. egistry checking e searched the International Clinical Trials Registry Plat- orm (ICTRP), the International Prospective Register of ystematic Review (PROSPERO), the Clinical Trials.gov reg- stry, and the University Hospital Medical Information etwork-Clinical Trials Registry (UMIN-CTR) up to October 1, 2012. ICTRP in the WHO Registry Network meets spe- ific criteria for content, quality and validity, accessibility, nique identification, technical capacity and administra- ion. Primary registries meet the requirements of the ICMJE. linical Trials.gov is a registry of federally and privately sup- orted clinical trials conducted in the United States (US) nd around the world. UMIN-CTR registers clinical trials con- ucted in Japan and around the world. andsearching, reference checking, and other e handsearched abstracts published in AAT and relevant ournals in Japan. We checked the references of included tudies for further relevant literature. eview methods election of trials n order to make the final selection of studies for the review, ll criteria were applied independently by four authors (e.g., H, JK, SP, and SO) to the full text of articles that had passed he first eligibility screening (Fig. 1). Disagreements and ncertainties were resolved by discussion with other author e.g., HK, KT, and YM). Studies were selected when (i) the design was a RCT and ii) one of the interventions was a form of AAT. Protocols ithout results were excluded, and we included only com- leted studies. Cure and rehabilitation effects were used as primary outcome measure. Trials that were excluded were resented with reasons for exclusion (Appendix). isk of bias (quality) assessment n order to ensure that variation was not caused by system- tic errors in the study design or execution, three review eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 uthors (HO, SP, and TH) independently assessed the qual- ty of articles. A full quality appraisal of these papers was ade using the Cochrane’s criteria list for the methodologi- al quality assessment.6 Disagreements and uncertainties dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 4 H. Kamioka et al. Table 1 The special search strategies. w S o s w d c b b g v c m S T H r B T b i j e i p t A P A c ( a ere resolved by discussion with other authors (e.g., HO, O, and HK). Each item was scored as ‘yes’ (y), ‘no’ (n), ‘do not know r unclear’ (?), or ‘not applicable’ (n/a). Depending on the tudy design, some items were not applicable. The ‘‘n/a’’ as excluded from calculation for quality assessment. We isplayed the percentage of present description on all 11- heck items for the quality assessment of articles. Then, ased on the percentage of risk of poor methodology and/or ias, each item was assigned to the following categories: ood description (80—100%), poor description (50—79%), or ery poor description (0—49%). Inter-rater reliability was alculated on a dichotomous scale using percentage agree- ent and Cohen’s kappa coefficient (k). Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h ummary of studies and data extraction en review authors (HP, HO, SH, TO, SP, TA, TH, JK, SO and K) described the summary from each article based on the ecommended structured abstracts.7,8 e a i i MEDLINE (n=141 ) CINAHL (n=154) Web of Science (n=123) Ichushi-Web (n=203 ) Global Healt h Librar y (n= 68 ) Western Pacifi c Regio n Index Medic us (n= 43 ) PsycINFO (n=193) Cochrane Datab ase of Syste matic Revi ews (n= 6) Data base of Abstract s of Re views of Effect s (n = 4) Cochrane Central Regist er of Controlle d Tria ls (n= 89 ) Coch rane Metho dology Re gister (n = 0 ) Health Technology Assessments Database (n= 1) NHS Econo mic Eval uati on Databas e (n= 1 ) Cochrane Coll aborati on data bases (n= 1 ) Campbel l Syste matic Revi ews (n= 14 ) Manuscripts based on databases Intern Unive Retrieved fo r detail evalua Articles meeting inclusion criteria ( Excluded (n=46) Figure 1 Flowchart enefit, harm, and cost he GRADE Working Group9 reported that the balance etween benefit and harm, quality of evidence, applicabil- ty, and certainty of the baseline risk were all considered in udgments about the strength of recommendations. Adverse vents (harm) and cost for intervention were especially mportant information for researchers and users of clinical ractice guidelines, and we presented this information with he description of each article. nalysis re-planned stratified analyses were: (a) trials comparing AT with no treatment or waiting list controls, (b) trials omparing different types of general rehabilitation methods e.g., physical therapy, occupational therapy), and (c) tri- ls comparing AAT with other different intervention(s). We eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 xpressed the results of each RCT, when possible, as rel- tive risk (RR) with corresponding 95 percent confidence ntervals (95%CI) for dichotomous data, and as standard- zed or weighted mean differences (SMD) with 95%CI for Clinical registries International Clinical Trial s Registry Platfor m (n= 7) ational Prospectiv e Regist er of Syste matic Revi ews (n=12 ) Cli nical Tria ls.go v (n=12 ) rsity Hospita l Medical Infor mation Networ k -Clinical Trials Registr y (n= 0 ) tion by articles (n=57) n=11) Appendix (references to studies excluded) Not rando mized con troll ed trial (n=20 ) Not curative effect (n=14) Not or iginal article (n= 3) Not detected (n= 2) Submit preparation a t presen t (n= 2 ) Not ani mal therapy (n= 2) Reduplication (n= 1 ) Not acceptable (n= 1) Not publishe d yet (n= 1) of trial process. dx.doi.org/10.1016/j.ctim.2013.12.016 IN+Model s c s s s t b f p t A t w f F v s t n s h f h m a w g p i e c t i d g f p a a s c r i a a p a t o e s o w ARTICLEYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy continuous data. Heterogeneous results of studies that pro- vided by inclusion criteria were not combined. Research protocol registration We submitted and registered our research protocol to the PROSPERO database (no. CRD42012003032),10 an interna- tional database of prospectively registered SRs in health and social care. Key features from the review protocol are recorded and maintained as a permanent record in PROSPERO. This provides a comprehensive listing of SRs reg- istered at inception, and enables comparison of reported review findings with what was planned in the protocol. PROS- PERO is managed by CRD and funded by the UK National Institute for Health Research (NIHR). Registration was rec- ommended because it encourages full publication of the review’s findings and transparency in changes to methods that could bias findings.11 Results Study selection The literature searches based on databases included poten- tially relevant articles (Fig. 1). Abstracts from those articles were assessed, and 57 papers were retrieved for further evaluation (checks for relevant literature). Forty-six pub- lications were excluded because they did not meet the eligibility criteria (see Appendix). Eleven studies12—22 met all inclusion criteria (Table 1). Study characteristics The language of all eligible publications was English. Target diseases and/or symptoms (Table 2) were schizophrenia,12,19,20 cancer,13 advanced heart failure,14 depression,15,21 ambulatory motor impairment,16 older adults admitted to skilled rehabilitation units,17 elderly persons with chronic psychiatric, medical, and neurologic conditions,18 and a mental illness diagnosis as well as a history of alcohol/drug abuse or other addictive behaviors.22 Based on ICD-10, we identified a disease targeted in each article (Table 3). Among 11 studies, seven studies were about ‘‘Mental and behavioral disorders (F10-19,22 F20,12,19,20 F30-33,15,21 and the unidentified due to includ- ing many geriatric disease18)’’. There was one study each in ‘‘Neoplasms (C00-D48; the unidentified due to many site of cancer)’’,13 ‘‘Diseases of the circulatory system (I50.1)’’,14 and ‘‘Injury, positioning and certain other consequences of external causes (T90-93)’’.16 Because there were a variety of target diseases, there was one article that we could not identify a single disease.17 Types of animal studied included dog,12—14,16,18,19 dog or cat, 20 dolphin,15 bird,17 cow,21 and dog, rabbit, ferret, and guinea pig.22 In a study for inpatients with schizophrenia,12 com- pared with the control group, the dog treatment group showed significant improvement on all measures expect Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h for social support and negative psychiatric symptoms. The results of the study showed that AAT can promote significant improvements in many clinical aspects among inpatients with schizophrenia. Similarly, in a study for inpatients with t c f PRESS 5 chizophrenia,19 the dog intervention group showed signifi- ant improvements in the living skill profile, social contact core, and in the positive and negative symptom dimen- ions. On the other hand, the control group also showed ignificant positive changes in positive and general symp- oms. No differences were found between the two groups efore and after the application of the intervention. As or elderly schizophrenic patients, a controlled 1-year study rovided subjects with their own dog or cat as the interven- ion animal, according to personal preference.20 The Social daptive Functioning Evaluation (SAFE) scores at termina- ion of the study showed significant improvement compared ith baseline scores, and were significantly more positive or the AAT group on both Total SAFE score and on the Social unctions subscale. A study tried to identify to what extent an AAT (i.e., isits with a dog) affects mood, self-perceived health, and ense of coherence among patients undergoing radiation herapy for cancer.13 Results showed no statistically sig- ificant differences within or between groups in mood, ense of coherence, or two facets of self-perceived ealth. An AAT was performed in patients hospitalized with heart ailure.14 The study tried to determine whether a 12-min ospital visit with a therapy dog improves hemodynamic easures, lowers neurohormone levels, and decreases state nxiety in patients with advanced heart failure. Compared ith controls, the volunteer-dog group had significantly reater decreases in systolic pulmonary artery pressure and ulmonary capillary wedge pressure during and after the ntervention. A study based on dolphins was performed to evaluate the ffectiveness of animal facilitated therapy with dolphins, ontrolling for the influence of the natural setting, in the reatment of mild to moderate depression.15 For the partic- pants who completed the study, the mean severity of the epressive symptoms was more reduced in the treatment roup than in the control group. A study reported the effectiveness of dog intervention or people with severe ambulatory disability.16 Significant ositive changes in all but two dependent measures were ssociated with the presence of a service dog both between nd within groups. Psychologically, all participants showed ubstantial improvements in self-esteem, internal locus of ontrol, and psychological well-being within six months after eceiving their dog. Socially, all participants showed similar mprovements in community integration. Demographically, ll participants showed increases in school attendance nd/or part-time employment. Economically, all partici- ants showed dramatic decreases in the number of both paid nd unpaid assistance hours. An avian interventional study was performed to examine he alleviation effect on depression, loneliness, and morale f older adults in skilled rehabilitation units.17 In the pres- nce of a companion bird, the experimental group showed a ignificant decrease in depression, but no decrease in morale r loneliness was observed in the control group that was ithout a bird. A dog interventional study was performed to evaluate eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 he effects on geriatric psychiatry inpatients.18 No signifi- ant differences in the Multidimensional Observation Scale or Elderly Subjects scores were found between or within dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 6 H . K am ioka e t al. Table 2 Brief summary of articles based on structured abstracts and additional elements. Reference no. 12 13 14 Author Chu CI, et al. Johnson RA. et al. Cole KM. et al. Citation J Psychosocial Nurs 2009;47:42—49 Oncology Nursing Forum 2008;35:225—232. Am J Crit Care 2007;16:575—585 Title The effect of animal-assisted activity on inpatients with schizophrenia Animal-assisted activity among patients with cancer: effects on mood, fatigue, self-perceived health, and sense of coherence Animal-assisted therapy in patients hospitalized with heart failure Aim/objective To evaluate the effects of animal-assisted activity on self-esteem, control over activities of daily living, and other psycho-physiological aspects among Taiwanese inpatients with schizophrenia To identify to what extent an animal-assisted activity (i.e., visits with a dog) affects the mood, self-perceived health, and sense of coherence among patients undergoing radiation therapy. To determine whether a 12-min hospital visit with a therapy dog improves hemodynamic measures, lowers neurohormone levels, and decreases state anxiety in patients with advanced heart failure Setting/place Psychiatric institution in Hualien Country, located in eastern Taiwan Outpatient radiation therapy units of two hospitals in a mid-sized, midwestern city, USA The cardiac care unit or the cardiac observation unit Participants 30 adult patients with schizophrenia 30 adult patients undergoing nonpalliative radiation therapy 76 adult patients with a diagnosis of advanced heart failure Intervention Weekly 50-min animal-assisted activity sessions were arranged for the patients of the treatment group over a period of 2 months. Patients in the control group received treatment as usual. The animal-assisted activity was held in the hospital’s garden but took place in the activity hall during inclement weather and during the first 2 weeks of the study so as not to distract the patients. The animals used in this study were two healthy, friendly, medium-sized, trained dogs of nonspecific breeds. They were provided by trainers, but during interactions with patients were accompanied only by the investigators Patients participated in 15-min sessions three times per week for four weeks. Dog visit group: Two visitor dogs used in the study were certified by the College of Veterinary Medicine at the University of Missouri Pet-assisted Love and support (PALS) program. Dogs were selected for quiet temperaments, friendliness with strangers, and length of visitation experience. During the sessions, participants combed, petted, played, and talked with the dog. The dog handlers introduced the dog to the participant during first session and were instructed to avoid conversation with the participants. Friendly human visit group: Participants met individually with the same adult. Friendly human visitors were volunteer nursing students, emeritus nursing faculty, hospital administrative staff from other departments, and community members. Reading group: Participants read silently researcher-provided magazines. Magazines were selected based on lack of content related to health and fitness, cancer and treatments, selfhelp, counseling, pets, AAA, and animal-assisted therapy Patients randomly assigned to the experimental group received a visit from a volunteer and a dog. The type of dog breed was not controlled for; 14 dogs of 10 various breeds were used. The 14 dogs included 1 extra-large dog, 6 large dogs, 5 medium dogs, and 2 small dogs. Each visit was conducted according to the guidelines taught during the volunteer and dog orientation: (1) volunteer introduces self and dog, (2) patient washes his or her hands before the visit, (3) dog lies on the bed with its head within 0.6 m (2 ft) of the patient’s head on a clean sheet used as a barrier to the patient’s bed, (4) patients may pet the dog and talk to the dog and volunteer and (5) patient washes his or her hands after the visit. No attempt was made to control the content of the conversation during the visit. The visit lasted for 12 min. After the visit, an instant self-developing photograph was taken of the patient with the dog and given to the patient. Patients randomly assigned to the volunteer-only group received a 12-min visit from a volunteer. The volunteer introduced himself or herself, sat in a chair approximately 1.2 m (4 ft) from the patient’s head, and let the patient know that the visit would last for 12 min if the patient was up to it. No attempt was made to control for the volunteer’s usual conversation during the visit. No patient requested to end any earlier than 12 min. Patients randomly assigned to the control group were asked to lie quietly without talking unless they had a specific need or request. For all groups, a sign was placed on the patient’s door or curtain asking everyone to please not interrupt the visit. Nurses assigned to patients to provide care were asked not to interrupt during the 12-min interaction and data collection, unless an emergency occurred. Volunteers participating in the volunteer-dog teams were used for the volunteer-only group as much as possible to minimize any influence of a volunteer’s personality on the results. For all groups, data were collected at baseline immediately before the visit, 8 min after the intervention started, and at 16 min, which was 4 min after the end of the visit Main and secondary outcomes Self-esteem, self-determination, extent of social support and increases and decreases in adverse psychiatric symptoms Mood:Profile of Mood States (POMS), Self-perceived health:Self-perceived health questionnaire, Sense of coherence:Orientation to Life Questionnaire(OTLQ), Exit questionnaire: Participants completed this five-item tool that was developed by the research team Heart rate, cardiac index, plasma levels of catecholamines, and anxiety Randomization No description Via a computer-generated random-numbering system Using a table of random numbers Blinding/masking No description No description Data collectors did not speak to the patients during the measurement of outcome variables and the intervention Numbers randomized Treatment group (n = 15) and control group (n = 15) The dog visit group (treatment group) (n = 10), friendly human visit group (n = 10), or quiet reading group (n = 10) Volunteer-dog team group (n = 26), volunteer only group (n = 25), and control group (n = 25) Recruitment The participants in this study were patients selected from a 600-bed psychiatric institution in Hualien County, located in eastern Taiwan 28 Caucasian and 2 African American adults with no known pet allergies who were beginning nonpalliative (first-line) radiation therapy for cancer for a period of at least four weeks following initial diagnosis 76 adults patients with a diagnosis of advanced heart failure admitted to the cardiac care unit or the cardiac observation unit Numbers analyzed Treatment group (n = 12) and control group (n = 15) The dog visit group (treatment group) (n = 10), friendly human visit group (n = 10), or quiet reading group (n = 10) Volunteer-dog team group (n = 26), volunteer only group (n = 25), and control group (n = 25) dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 Effe ctive n e ss of an im al-assiste d th e rap y 7 Outcome Compared with the control group, the treatment group showed significant improvement on all measures except for social support and negative psychiatric symptoms. The results of this study showed that animal-assisted activity can promote significant improvements in many clinical aspects among inpatients with schizophrenia No statistically significant differences were found within or between groups in mood, sense of coherence, or two facets of self-perceived health. However, participants described each of the three activities as beneficial Compared with controls, the volunteer-dog group had significantly greater decreases in systolic pulmonary artery pressure during (−4.32 mm Hg) and after (−5.78 mm Hg) and in pulmonary capillary wedge pressure during (−2.74 mm Hg) and after (−4.31 mm HG) the intervention. Compared with the volunteer-only group, the volunteer-dog group had significantly greater deceases in epinephrine levels during (−15.86 pg/mL) and after (−17.54 pg/mL) and in norepinephrine levels during (−232.36 pg/mL) and after (−240.14 pg/mL) the intervention. After the intervention, the volunteer-dog group had the greatest decrease from baseline in state anxiety sum score compared with the volunteer-only (−6.65 units) and the control groups (−9.13 units) Harm Three patients who were afraid of dog did not participate in the animal-assisted activity No dog allergy No description Conclusion Animal-assisted activity should be integrated into the treatment of institutionalized patients with schizophrenia This study was one of few involving AAA (animal-assisted activity) among patients with cancer in a randomized design. One issue that may have affected the findings of present study is that disease progression during the time of the intervention was not measured. Side effects of radiation therapy were not assessed. Further research is needed with larger samples to identify whether the effects are statistically recognizable Animal-assisted therapy improves cardiopulmonary pressures, neurohormone levels, and anxiety in patients hospitalized with heart failure Trial registration No description No description No description Fund Nothing No description Grant 01061809 from the Pet Care Trust Foundation, Quilcene, Washington Cost of intervention No description Dog visits are no more costly than human visits because all organizations provide dog visits on a volunteer basis No description 15 16 17 Author Antonioli C, et al. Allen K, et al. Jessen J, et al. Citation BMJ 2005;331 JAMA 1996;275:1001—1006 Psychological Reports 1996;78:339—348 Title Randomised controlled trial of animal facilitated therapy with dolphins in the treatment of depression The value of service dogs for people with severe ambulatory disabilities Avian companionship in alleviation of depression, loneliness, and low morale of older adults in skilled rehabilitation units Aim/objective To evaluate the effectiveness of animal facilitated therapy with dolphins, controlling for the influence of the natural setting, in the treatment of mild to moderate depression and in the context of the biophilia hypothesis To assess the value of service dogs for people with ambulatory disabilities To examine the effect of a caged bird on depression, loneliness, and morale of older adults in skilled rehabilitation units Setting/place The study was carried out in Honduras, and recruitment took place in the United States and Honduras Environments of study participants Two skilled rehabilitation units in Nebraska Participants Outpatients, recruited through announcements on the internet, radio, newspapers, and hospitals Forty-eight individuals with severe and chronic ambulatory disabilities requiring use of wheelchairs who were recruited from advocacy and support groups for persons with muscular dystrophy, multiple sclerosis, traumatic brain injury, and spinal cord injury 40 older adults in a skilled rehabilitation unit, self-reported measures of depression, loneliness, and morale dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 8 H . K am ioka e t al. Table 2 (Continued) Intervention Participants were asked to play, swim, and take care of the animals. They had an introductory session, to explain about dolphin behavior and water safety. The first part of the trial, which took half an hour, was structured so the participants could familiarize themselves with the animals. Participants were standing in the water, close to the trainer. The dolphin, following the trainer’s signals, performed trained behaviors (such as a jump or a swim). Participants were able to touch the dolphins when close to the trainer. The second part of the trial, another half an hour, was unstructured, and free and spontaneous interactions occurred. Participants were snorkeling in the water with the dolphins. In the control group, participants were assigned to an outdoor nature program featuring the same water activities as the animal care program but in the absence of dolphins, to control for the influence of water and other, non-specific, environmental factors. In the outdoor nature program, participants had to swim and snorkel in the barrier coral reef for 1 h a day and had a similar degree of individualized human contact as in the animal care program. Participants were informed of the marine ecosystem, the barrier coral reef (the second largest in the world after the great barrier reef of Australia), and water safety. Both programs were run simultaneously and lasted for a period of two weeks for each group. The treatments were given daily, Monday to Friday, 1 h per day Individuals assigned to the experimental group received assistance dogs 1 month after the study began (in 1990), and subjects in the wait-list control group 12 months later (13 months after the study began). Dogs were made available to participants in this study through trainers dedicated to providing dogs to people with disabilities. All the dogs were initially raised in family environments to socialize them. The dogs then entered training designed to teach them how to provide general assistance. Following this, each dog was paired with a person with a disability and was given individualized special training to expand the dog’s commands to meet the unique needs of the person to whom it was assigned and to ensure that the person with a disability learned to handle the dog effectively A bird was placed in the room of each subject in the experimental group. Care for the birds was provided either at times the subject was not in the room or by having a staff member bring the bird and cage out of the room so that there was no intervention by the investigator through interaction with the subject. The control group had no intervention other than their routine care in the unit. At the end of 10 days, the three instruments were administered again to all subjects (post-test), and the bird was removed. Although a relatively short time period, 10 days was the maximum amount of time it could be predicted that a sufficiently large sample would still be in the institution Main and secondary outcomes Hamilton rating scale for depression, the Beck depression inventory, and the Zung self rating anxiety scale Self-reported assessments of psychological well-being, internal locus of control, community integration, school attendance, part-time work status, self-esteem, marital status, living arrangements, and number of biweekly paid and unpaid assistance hours Morale, depression, and loneliness Randomization Random number table to generate the block allocation sequence Individuals were matched on several characteristics, including age, sex, marital status, race, and the nature and severity of the disability, to create 24 pairs. Within each pair, individuals were randomly assigned to either the experimental or the wait-list control group No description Blinding/masking The allocation sequence was concealed until treatments were assigned. We kept the randomization sequence hidden from the investigators giving the treatments by using a set of opaque numbered sealed envelopes, each containing the allocation for one patient No description No description Numbers randomized Animal care program group (n = 15) and outdoor nature program group (n = 15) Experimental group (n = 24) and wait-list control group (n = 24) Experimental group (n = 20) and control group (n = 20) Recruitment Field research work took place at the Roatan Institute for Marine Sciences (Roatan, Bay Islands, Honduras) between July 2002 and December 2003. After participants had read the information, we asked them for a medical certificate from their treating therapist Qualifying individuals from New York, Pennsylvania, Massachusetts, and Connecticut were contacted through advocacy support groups (for example, the Muscular Dystrophy Association, the Multiple Sclerosis Association) A sample of older adults admitted to two midwestern, skilled rehabilitation units participated dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 Effe ctive n e ss of an im al-assiste d th e rap y 9 Numbers analyzed Animal care program group (n = 13) and outdoor nature program group (n = 12) Experimental group (n = 24) and wait-list control group (n = 24) Experimental group (n = 20) and control group (n = 20) Outcome Of the 30 patients randomly assigned to the two groups of treatment, two dropped out of the treatment group after the first week and three withdrew their consent in the control group after they had been randomly allocated. For the participants who completed the study, the mean severity of the depressive symptoms was more reduced in the treatment group than in the control group (Hamilton rating scale for depression and Beck depression inventory). For the sample analyzed by modified intention to treat and last observation carried forward, the mean differences for the Hamilton and Beck scores between the two groups was highly significant Significant positive changes in all but two dependent measures were associated with the presence of a service dog both between and within groups. Psychologically, all participants showed substantial improvements in self-esteem, internal locus of control, and psychological well-being within 6 months after receiving their service dog. Socially, all participants showed similar improvements in community integration. Demographically, all participants showed increases in school attendance and/or part-time employment. Economically, all participants showed dramatic decreases in the number of both paid and unpaid assistance hours With the presence of a companion bird, the experimental group (n = 20) showed a significant decrease in depression compared to no decrease in morale or loneliness from the control group (n = 20) who were without a bird Harm No description No description No description Conclusion The therapy was effective in alleviating symptoms of depression after two weeks of treatment. Animal facilitated therapy with dolphins is an effective treatment for mild to moderate depression, and is based on a holistic approach, through interaction with animals in nature Trained service dogs can be highly beneficial and potentially cost-effective components of independent living for people with physical disabilities Use of a companion bird may lessen negative effects of change of residence for older adults Trial registration No description No description No description Fund The Tursiops Society Onlus and the advice and support given by Andrew Weil and Brian Becker of the University of Arisona, USA; Stephen Kellert of Yale University, USA; and Costantino Balestra of the Universite Libre de Bruxelles, Belgium. We thank Yvonne Hartgers, Arnoldo Javier Montoya Stone, Aida Lagos, Hector Murcia Pinto for medical, phycological diagnosis and assistance; the research participants, the Psychiatric Hospital of Tegucigalpa and Roatan Hospital No description No description Cost of intervention No description Total calculated costs of initial canine training at $10,000, lost investment income on initial training costs at 5% per annum compounded quarterly; $1000 per year in animal maintenance; an expected canine service period of 8 years; and $8, $10, and $12 per hour for paid human assistance No description Reference no. 18 19 20 Author Zisselman MH, et al. Villalta-Gil V, et al. Barak Y, et al. Citation The American Journal of Occupational Therapy 1996;50:47—51 Anthrozoos 2009;22:149—159 Am J Geriatr psychiatry 2001;9:439—442 Title A pet therapy intervention with geriatric psychiatry inpatients Dog-assisted therapy in the treatment of chronic schizophrenia inpatients Animal-assisted therapy for elderly schizophrenic patients Aim/objective To evaluate the effects of pet therapy on geriatric psychiatry inpatients To assess the effectiveness of including a trained therapy dog in an intervention program applied to institutionalized patients with chronic schizophrenia To evaluate the effects of AAT on long-stay geriatric schizophrenic patients in a controlled 1-year study Setting/place The 26-bed Wills Eye Hospital Geriatric Psychiatric Unit in Philadelphia Saint John of God-Mental Health Services Hospital The word of Kibbutz Givat Haim Ichud, Israel Participants Elderly persons with chronic age-related psychiatric, medical, and neurologic conditions such as depression, dementia, Parkinson’s disease, stroke, and accompanying medical disorders No description 20 adult patients with schizophrenia dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 10 H . K am ioka e t al. Table 2 (Continued) Intervention Intervention was provided for 5 consecutive days for each group. The intervention for the experimental group consisted of a 1-h visit with dogs. The subjects had contact with and fed the visiting dogs, were encouraged to reminisce about their own experiences with pets and other animals, and heard a brief talk about the dogs. The control group exercised for 1 h a day while the experimental group was visiting with the dogs. Adherence to both treatments of the subject’s daily schedule remained the same. Additionally, all subjects continued receiving their psychotropic medications and individual and group psychotherapy sessions The intervention program was applied by a trained psychologist. It consisted of 25 sessions of 45 min each; two sessions were given per week. The intervention group with therapy dog (LG + D) was directed by the psychologist, who was assisted by a two-year-old, female Labrador, certified as a therapy dog. The dog was accompanied by her handler. The group without a dog (lG) was directed by the same psychologist. The intervention was based on Integrated Psychological Treatment (lPT) designed by Brenner et al. (1994). This treatment for patients with schizophrenia has been developed to work as much on cognitive functioning as on social functioning. It is a group intervention structured program with five subprograms: cognitive differentiation, social perception, verbal communication, social skills training, and interpersonal problem solving. They are hierarchically ordered, so the first interventions are directed to basic cognitive skills, the next interventions transform the cognitive skills into social and verbal behaviors, and the last ones train the patients in the solution of more complex interpersonal problems. Sessions for the Lg + D group were designed so that the handler interacted with the dog and the therapist, the therapist interacted with the patient and the handler, and patients interacted with the dog and therapist. This design was used in order to minimize interactions between handler and patients, as the handler was not present in the lG group AAT was undertaken once weekly on the same day. The therapists and assisting animals came to the ward at 10:30 am, and the group session lasted 3 h. Three AAT counselors from the PET (Pet Enrichment Therapy) program at Kibbutz Givat Haim Ichud, Israel, were regularly accompanied by a psychiatric nurse, providing a ratio of 1:2.5 caretakers to patients. Each patient was provided with his own dog or cat, according to personal preference. Sessions included ‘‘ADL modeling activities’’ such as petting, feeding, grooming, bathing, and teaching the animals to walk on a lead for greater mobility. Control-group patients were assembled for reading and discussion of current news for a similar duration on the same days that AAT was undertaken. These sessions were conducted by three certified nurses so as to keep the ratio of staff to patients equal to that of the AAT group Main and secondary outcomes Self-care functioning, disoriented behavior, depressed or anxious mood, irritable behavior, and withdrawn behavior Symptoms, social competence, and subjective perception of quality of life. A schedule assessing adverse reactions to animals, the Wechsler Adult Intelligence Scale, and the Mini Mental State Examination were used as screening instruments, in order to confirm inclusion of patients into the sample. Social-Adaptive Functioning Evaluation (SAFE) Randomization No description 24 patients with chronic schizophrenia were randomly selected from a computerized register No description Blinding/masking The nursing staff member was also blind to group assignments All patients were evaluated by a trained psychologist blind to the patient’s intervention group at baseline and after the intervention program (patients were asked not to mention details about the therapy sessions and the psychologist was also not supposed to gather information about their intervention group) Assessor (clinical psychologist) Numbers randomized Per therapy intervention (n = 33) or an exercise intervention (n = 25) Intervention group with therapy dog (n = 12) and control group without a dog (n = 12) Animal assisted treatment group (n = 10) and control group (n = 10) Recruitment Elderly persons with chronic age-related psychiatric, medical, and neurologic conditions such as depression, dementia, Parkinson’s disease, stroke, and accompanying medical disorders Only those patients staying at Long Term Care facilities were included; these patients cannot live in the community, due to their social and clinical characteristics. A long course of the disorder and cognitive or social deficits characterizes patients staying in these facilities Subjects in the study were 20 chronic schizophrenic patients, who were long-stay residents at the Abarbanel Mental Health Center, Bat Yam, Israel dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 Effe ctive n e ss of an im al-assiste d th e rap y 11 Numbers analyzed Per therapy intervention (n = 33) or an exercise intervention (n = 25) Intervention group with therapy dog (n = 12) and control group without a dog (n = 9) Animal assisted treatment group (n = 10) and control group (n = 10) Outcome No significant differences in the Multidimensional Observation Scale for Elderly Subjects (MOSES) scores were found between or within groups before and after the interventions. There was a nonsignificant tendency for subjects who received the pet intervention to have less irritable behavior after treatment. However, women with dementia who received either pet therapy or exercise intervention had improved irritable behavior scores after treatment Patients in the lG + D group showed significant improvements in the LSP social contact score, in the positive and negative symptom dimension and total score of the PANSS, and in quality of life related with social relationships. Patients in the lG group showed significant positive changes in positive and general symptoms and total PANSS score. No differences were found between the two groups before and after the application of the intervention The Social Adaptive Functioning Evaluation scores at termination showed significant improvement compared with baseline scores and were significantly more positive for the AAT group on both Total SAFE score and on the Social Functions subscale Harm No description Nothing No description Conclusion This pilot study demonstrates the need for further research on animal-assisted interventions with hospitalized elderly persons. Differential improvement in women with dementia also requires further investigation Introducing a dog into the psychosocial intervention for patients with schizophrenia produced some positive outcomes. However, the results of the study are not conclusive and must be interpreted cautiously AAT proved a successful tool for enhancing socialization, ADLs, and general well-being Trial registration No description No description No description Fund A grant from Sandoz/Jeffs Companion Animal Center The financial help of the La Caixa Foundation and was supported by the Spanish Ministry of Health, Instituto de Salud Carlos lll, CIBERSAM. The authors declare that no competing interests exist No description Cost of intervention No description No description No description Reference no. 21 22 Author Pedersen I, et al. Carolyn AM, et al. Citation Anthrozoos 2012;25:149—160 Anthrozoos 2000;13:43—47 Title Farm animal-assisted intervention for people with clinical depression: a randomized controlled trial Animal-assisted therapy in psychiatric rehabilitation Aim/objective To examine potential changes in mental health in people with clinical depression, while working with farm animals as the only task on the farm To evaluate whether patients in the animal-assisted therapy group would show a greater increase in observed appropriate social behaviors than the control group patients who did not receive animal-assisted therapy Setting/place Eleven dairy farms from six different counties in Norway Terrell State Hospital, Terrell, Texas Participants 28 adult patients with clinical depression 69 inpatient participants at a large state psychiatric facility Intervention The intervention consisted of work and interaction with farm animals twice a week for 12 weeks. The time for each session spent on the farm per day varied from 1.5 to 3.0 h due to differences in farm size, degree of mechanization, and the amount of work. A first introductory visit was used by the participants to get familiar with the farm and farmer. On the following visit, the participants worked together with the farmer in the cowshed. The participants were allowed to choose work such as grooming, mucking, feeding, taking care of the calves, and milking. They could also choose to spend their time in physical contact with the animals. The participants did not take part in any other work at the farm The experimental AAT group had animals visit the class each day. The animals included dogs, rabbits, ferrets, and guinea pigs. The animals remained for the entire class period and were moved from patient to patient. Patients in the group were allowed to observe the animals or interact with the animals — hold them, pet them, and/or play with them as long as they did not disrupt the group. Patients were not required to participate directly with any animals; such participation was voluntary and the patients determined the level of individual involvement. However, there was only one female patient out of all of the AAT subjects that elected to not interact directly with the animals dx.doi.org/10.1016/j.ctim.2013.12.016 P le ase cite th is article in p re ss as: K am ioka H , e t al. Effe ctive n e ss of an im al-assiste d th e rap y: A syste m atic re vie w of ran d om ize d con trolle d trials. C om p lem en t T h er M ed (2014), h ttp ://d x.d oi.org/10.1016/j.ctim .2013.12.016 A R T IC L E IN P R E S S +M odel Y C T IM -1299; N o. of Page s 20 12 H . K am ioka e t al. Table 2 (Continued) Main and secondary outcomes Depression anxiety, and self-efficacy Social Behavior Scale Randomization The randomization was conducted by a researcher blinded to farm and participants No description Blinding/masking No description It was not possible to keep the rater blind to condition since the behavior observations were made daily while the group was being conducted. However, neither those conducting the class nor the rater was privy to the design or intent of the study, and hence they remained essentially ‘‘blind’’. Data entry was by an individual who was also blind to the treatment conditions Numbers randomized The intervention group (n = 16) and the control group (n = 13) Animal-assisted therapy group (n = 18) and control group (n = 19) Recruitment Thirty-five participants were recruited through advertisements, invitation letters from the Norwegian Labour and Welfare Service, and contact with health personnel. Potential participants received a letter describing the intervention, and the possibility to be allocated to either a control or an intervention group was stated There were 69 inpatient participants (70% male and 30% female) at a large state psychiatric facility Numbers analyzed The intervention group (n = 16) and the control group (n = 13) Animal-assisted therapy group (n = 18) and control group (n = 19) Outcome A significant decline in depression and a significant increase in self-efficacy were seen in the intervention group between recruitment and of intervention. In the control group, no significant changes were found. No significant differences were found when comparing change in mental health measures in the intervention and control groups. However, more subjects in the intervention group (6) than in the control group (1) had clinically significant change, indicating that animal-assisted intervention in Green care could be beneficial for subgroups of clients and act as a useful supplement within mental health care Animal-assisted therapy patients interacted more with other patients. Similarly, there was a main effect for weeks, with improvement in scores over time but no interaction between weeks and groups. There was a similar finding for the AAT group; patients smiled and showed pleasure significantly more often than the control group patients and thus improved over the four weeks with no interaction between weeks and groups Harm No description No description Conclusion Those who participated in animal-assisted therapy experienced statistically significant changes in depression and generalized self-efficacy. Although the changes were not significantly different from those in the control group, more participants in the intervention could be beneficial for subgroups of clients and act as a useful supplement within mental health care These data suggest that AAT plays an important role in enhancing the benefits of conventional therapy and demonstrates the benefit of including a non-AAT group for comparison. The study also demonstrates the importance of using longitudinal, repeated measure designs. Previous studies may have failed to find significant effects because they were restricted to shorter intervals for measuring outcomes Trial registration No description No description Fund A grant from the Research Council of Norway, and Agricultural Agreement No description Cost of intervention No description No description dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy 13 Table 3 International classification of target diseases in each article. Chapter ICD code Classification Reference no. (detail ICD code) 1 A00-B99 Certain infectious and parasitic diseases 2 C00-D48 Neoplasms 13 (the unidentified due to many site of cancer) 3 D50-D89 Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism 4 E00-E90 Endocrine, nutritional and metabolic diseases 5 F00-F99 Mental and behavioral disorders 12,19—20 (F20), 15,21 (F30-33), 18 (the unidentified due to including many geriatric diseases), 22 (F10-19) 6 G00-G99 Diseases of the nervous system 7 H00-H59 Diseases of the eye and adnexa 8 H60-H95 Diseases of the ear and mastoid process 9 I00-I99 Diseases of the circulatory system 14 (I50.1) 10 J00-J99 Diseases of the respiratory system 11 K00-K93 Diseases of the digestive system 12 L00-L99 Diseases of the skin and subcutaneous tissue 13 M00-M99 Diseases of the musculoskeletal system and connective tissue 14 N00-N99 Diseases of the genitourinary system 15 O00-O99 Pregnancy, childbirth and the puerperium 16 P00-P96 Certain conditions originating in the perinatal period 17 Q00-Q99 Congenital malformations, deformations and chromosomal abnormalities 18 R00-R99 Symptoms, signs and abnormal clinical and laboratory finding not elsewhere classified 19 S00-T98 Injury, positioning and certain other consequences of external causes 16 (T90-93) 20 V00-Y98 External causes of morbidity and mortality 21 Z00-Z99 Factors influencing health status and contact with health services 22 U00-U99 Code for special purpose — Unidentified Because many illnesses were mixed, we could not identify it. 17 a g S w b t c o g Q W m q 1 groups before and after the interventions. There was a non-significant tendency for subjects who received the dog intervention to have less irritable behavior after treat- ment. However, women with dementia who received either pet therapy or exercise intervention had improved irritable behavior scores after treatment. A unique study was performed to examine potential changes in mental health in people with clinical depression who were working with farm animals as the only task on a farm.21 The intervention consisted of work and interac- tion with farm animals twice a week for 12 weeks. Those who participated in animal-assisted therapy experienced statistically significant changes in depression and gener- alized self-efficacy. Additionally, more participants in the intervention could have been beneficial for the subgroups of clients and served as a useful supplement within mental health care, although these changes were not significantly different from those in the control group. Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h A study evaluated whether patients such as those with a mental illness diagnosis as well as a history of alcohol/drug abuse or other addictive behaviors in the AAT group would show a greater increase in observed fi I d t ppropriate social behaviors than patients in the control roup.22 AAT patients interacted more with other patients. imilarly, there was a main effect that lasted for weeks, ith improvement in scores over time but no interaction etween weeks and groups. There was a similar finding for he AAT group; patients smiled and showed pleasure signifi- antly more often than the control group and thus improved ver four weeks, with no interaction between weeks and roups. uality assessment e evaluated 11 items from the Cochrane’s criteria list in ore detail (Table 4). Inter-rater reliability metrics for the uality assessment indicated substantial agreement for all 21 items (percentage agreement 97% and k = 0.939). This assessment evaluated the quality of how the main eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 ndings of the study were summarized in the written report. n general, there was a remarkable lack of execution and/or escription in the concealment, blinding, and intention-to- reatment (ITT) analysis. The items for which the description dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 14 H. Kamioka et al. Table 4 Evaluation of the quality of methodology for each article. No Criteria list Reference no. Present description 12 13 14 15 16 17 18 19 20 21 22 No/11 Rate (%) 1 Was the method of randomization adequate? ? y y y y y ? y n y ? 7 64% 2 Was the treatment allocation concealed? ? n ? y y y y y ? n ? 5 45% 3 Were the groups similar at baseline regarding the most important prognostic indicators? y y y y y y y y y y y 11 100% 4 Was the patient blinded to the intervention? ? n ? y y y n n n n y 4 40% 5 Was the care provider blinded to the intervention? ? n n y ? ? y n n n y 3 27% 6 Was the outcome assessor blinded to the intervention? ? ? ? n ? n ? y y n y 3 27% 7 Were cointerventions avoided or similar? y n y y y y y ? ? y y 8 73% 8 Was the compliance acceptable in all groups? y y y y y y y y ? y y 10 91% 9 Was the drop-out rate described and acceptable? y y y y n n y y y n y 8 73% 10 Was the timing of the outcome assessment in all groups similar? y y y y y y y y y y y 11 100% 11 Did the analysis include an intention-to-treat analysis? n n y y y n n ? n y y 5 45% Present description no/11 5 5 7 10 8 7 7 7 4 6 9 — — Rate (%) 45% 45% 64% 91% 73% 64% 64% 64% 36% 55% 82% — — w f c v i t a M T d o a c A T d p a ( C T i w n e c i t c t D T o e s r p y, yes; n, no; ?, do not know or unclear; n/a, not applicable. as lacking (very poor; <50%) in many studies were as ollows (present ratio; %): ‘‘Was the treatment allocation oncealed?’’ (45%); ‘‘Was the patient blinded to the inter- ention?’’ (40%); ‘‘Was the care provider blinded to the ntervention?’’ (27%); ‘‘Was the outcome assessor blinded o the intervention?’’ (27%); and ‘‘Did the analysis include n ITT analysis?’’ (36%). eta-analysis here were three RCTs on schizophrenia and two RCTs on epression. We could not perform a meta-analysis because f heterogeneity by difference of outcome measurement nd intervention method (e.g., in dog, and in dog or at). dverse events wo studies reported no adverse events,13,19 and one study Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h escribed three patients who were afraid of dogs and did not articipate in the intervention.12 There were no descriptions bout adverse events in the other eight studies14—18,20—22 Table 2). f a e osts of intervention wo studies13,16 described information about the cost of ntervention (Table 2). Johnson et al. showed that dog visits ere no more costly than human visits because all orga- izations provide dog visits on a volunteer basis.13 Allen t al. showed that the total calculated costs of initial anine training was $10,000, lost investment income on nitial training costs was 5% per annum compounded quar- erly, animal maintenance was $1000 per year, the expected anine service period was 8 years, and paid human assis- ance ranged from $8 to $12 per hour. iscussion his is the first SR of the cure effectiveness of ATT based n RCTs. Our study is unique because it summarized the vidence for each target disease according to ICD-10 clas- ification. We assume that this study will be helpful to esearchers who want to understand the effect of ATT com- rehensively, and it could provide indispensable information eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 or the organization that is going to make the guidelines ccording to each disease. Among the 11 RCTs that were identified, target dis- ases and/or symptoms included schizophrenia, depression, dx.doi.org/10.1016/j.ctim.2013.12.016 IN+Model p w m c O M n o t p o v d w w a i i t m m a t A e i t d o v F T c a w s d d p p t a ‘ s a ‘ t v w ARTICLEYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy cancer, advanced heart failure, severe ambulatory disabil- ity, older adults admitted to skilled rehabilitation units, elderly persons with chronic psychiatric, medical, and neu- rologic conditions, and a mental illness diagnosis, as well as a history of alcohol/drug abuse or other addictive behaviors, and intervention methods included various approaches such as dog, dolphin, bird, cat, cow, rabbit, ferret, and guinea pig. Tendency of target disease and outcome The most commonly reported target diseases were ‘‘Mental and behavioral disorders (F10-20, 30—33, and unclear)’’,12,15,17—22 and the effect of AAT on these diseases was improved mental health (e.g., anxiety and mood), QoL, and social behavior. The main reason given in these arti- cles for improved mental health was that the feeling and memory of an animal allowed the patient to be comfort- able, pleasant, and happy. For example, Le Roux and Kemp23 reported the following narrative comments by participants: ‘‘we talked to each other about the dog’’, ‘‘visits from the dog made me think about my own dog when I was young’’, and ‘‘at night I think about Pietie (the dog) and I smile’’. In studies about the effects of AAT on anxiety, discomfort, fear, and pain, AAT has been variably applied as an accessory treatment for persons with addictions such as alcohol/drug abuses22 and as evasion of direct discomfort for undergoing medical treatment for cancer.13 The other reported target diseases were ‘‘Diseases of the circulatory system (I50.1)’’14 and ‘‘Injury, positioning, and certain other consequences of external causes (T90- 93)’’.16 The former evaluated hemodynamic parameters, cardiac index, and neurohormone levels as primary out- comes. The latter assessed psychological variables such as well-being, internal locus of control, and community inte- gration. Improvements seen in these studies were mainly due to effects of buffering a person’s reactivity to mental stressor24,25 and providing a sense of comfort and safety, and diverting attention away from the immediate stressors to a more pleasurable and calming interaction.26 Validity of overall evidence based on quality assessment Overall evidence and quality assessment The Cochrane’s list is the most important tool related to the internal validity of trials. In this SR, there were seri- ous problems with the conduct and reporting of the target studies. Our review especially detected omissions of the fol- lowing descriptions: method used to generate concealment, blinding, and ITT analysis. Descriptions of these items were lacking (very poor; <50%) in many studies. In the Cochrane Review,27 the eligibility criteria for a meta-analysis are strict, and for each article, heterogene- ity and low quality of reporting must first be excluded. We could not perform a meta-analysis. Due to poor methodo- Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h logical and reporting quality and heterogeneity, there was insufficient evidence in the studies of AAT, and we are there- fore unable to offer clearly any conclusions about the effects of AAT based on RCTs. n n d c PRESS 15 Moreover, the CONSORT 201028 and the CONSORT for non- harmacological trials checklists29 are relatively new, but it as shown that the study protocol description and imple- entation for AAT studies should be subjected to these hecklists. verall evidence ost importantly, a specific adverse effect or harmful phe- omenon such as allergy or fear for animals was not clearly bserved overall, although we should consider the limita- ions and biases of these findings in the context of AAT atients/participants who are likely to enjoy animals. In ther words, a person who dislikes animals will refuse inter- ention from the beginning. The results of this study suggested that the RCTs con- ucted have been of relatively low quality. Only two RCTs ere evaluated as ‘‘good description (80—100%)’’.15,22 AAT ith dolphins is an effective treatment for mild to moder- te depression, and is based on a holistic approach through nteraction with animals in nature.15 AAT also plays an mportant role in enhancing the benefits of conventional herapy in psychiatric rehabilitation.22 Furthermore, AAT ay have positive effects on schizophrenia and/or serious ental disorders. We assume that the direct effects of AAT re generally improvement of mental health, elimination of he sense of isolation, and an improvement in QoL. Although further accumulation of RCT data is necessary, AT may be effective treatment for the following dis- ases and symptoms: cancer and/or advanced life-limiting llnesses that affect mental state and QoL, impaired circula- ory function with mechanical assistance, autistic spectrum isorders involving communicative skills, and self-reported utcomes for hospitalized patients and other patients with arious clinical conditions. uture research agenda to build evidence able 5 shows the future research agenda for studies of the ure effect by AAT. Researchers should use the appropri- te checklists for research design and intervention methods, hich would lead to improvement in the quality of the tudy, and would contribute to the accumulation of evi- ence. Researchers should also present not only efficacy ata, but also a description of any adverse events or harmful henomena and the reasons for withdrawals and non- articipation. Many studies in this review did not describe hese factors. As a gradual increase of intervention is necessary in cure nd rehabilitation programs, it is easy to assign settings like ‘Stage’’ for the intervention, such as first stage and second tage. Therefore, we also expect to understand the results nd detailed descriptions of ‘‘pragmatic trials’’30 as well as ‘explanatory trials’’ for the treatment effect by AAT. Bowen et al.31 suggested that public health is moving oward the goal of implementing evidence based inter- ention. But the feasibility of possible interventions, and hether comprehensive and multilevel evaluations are eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 eeded to justify them, must be determined. It is at least ecessary to show the cost of such interventions. Intro- uction of an interventional method must be based on its ost—benefit, cost—effectiveness, and cost—utility. dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 16 H. Kamioka et al. Table 5 Overall evidence and future research agenda to build evidence. Overall evidence in the present Research agenda After having premised study environment limited to the people who liked animals very much, AAT may be an effective treatment for mental and behavioral disorders such as depression, schizophrenia, and alcohol/drug addictions, and is based on a holistic approach, through interaction with animals in nature. 1. Satisfactory description and methodology including the CONSORT 2010 and the CONSORT for nonpharmacological trials 2. Description of the reason of participants refused (non-participation) 3. Description of adverse effects (e.g., allergy, infection, bit, and fear) and withdrawals 4. Description of intervention dose (if pragmatic intervention) 5. Description of cost 6. Development of the original check-list for AAT c r t a b a S T i ( p a i a T t m a i d l r w r s p a C I m b a t w ( n a C T a a S i f F T R H M C N E N D N Acknowledgements In addition, AAT as an intervention is unique and ompletely different than pharmacological or traditional ehabilitation methods. Therefore, it may be necessary o add some original items like herbal intervention,32 cupancture,33 traditional Chinese medicine34 and alneotherapy35 to the CONSORT 2010 checklist as lternative and/or complementary medicines. trength and limitations his review had several strengths: (1) the methods and mplementation registered high on the PROSPERO database; 2) it was a comprehensive search strategy across multi- le databases with no data restrictions; (3) there were high greement levels for quality assessment of articles; and (4) t involved detailed data extraction to allow for collecting all rticles’ content into a recommended structured abstract. he conduct and reporting of this review also aligned with he PRISMA statement36 for transparent reporting of SRs and eta-analyses. This review had several limitations that should be cknowledged. Selection criteria were common across stud- es, as described above; however, bias remained due to ifferences in eligibility for participation in each study. Pub- ication bias was a factor. Although there was no linguistic estriction in the eligibility criteria, we searched studies ith only English and Japanese key words. In addition, this eview reported on a relatively small and heterogeneous ample of studies. Moreover, we could not follow standard rocedures for estimating the effects of moderating vari- bles. onclusion n a study environment limited to the people who like ani- als, AAT may be an effective treatment for mental and ehavioral disorders such as depression, schizophrenia, and lcohol/drug addictions, and is based on a holistic approach Please cite this article in press as: Kamioka H, et al. Effectiv randomized controlled trials. Complement Ther Med (2014), h hrough interaction with animals in nature. To most effectively assess the potential benefits of AAT, it ill be important for further research to utilize and describe 1) RCT methodology when appropriate, (2) the reasons for W H S s on-participation, (3) intervention dose, (4) adverse effects nd withdrawals. ontributors H, JK, SP, SO, HO, SH, HP, TO, and TA conceived the study nd take responsibility for the summary of included studies nd data extraction. KT and YM are the guarantors. HK and O designed the study. HO, SP, TH and HK assessed the qual- ty of articles. All authors critically described the manuscript or important intellectual content. unding his study was supported by the Health and Labour Sciences esearch Grants (Research on Health Security Control: ID No. 24-021; representative; Dr. Tsutani K) from the Japanese inistry of Health, Labour and Welfare of Japan in 2012. onflict of interest statement one declared. thical approval ot required. ata sharing o additional data available. eness of animal-assisted therapy: A systematic review of ttp://dx.doi.org/10.1016/j.ctim.2013.12.016 e would like to express our appreciation to Ms. Rie igashino and Ms. Rinako Kai (paperwork), and Ms. Satoko ayama (all searches of studies) for their assistance in this tudy. dx.doi.org/10.1016/j.ctim.2013.12.016 Please cite this article in press as: Kamioka H, et al. Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials. Complement Ther Med (2014), http://dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy 17 Appendix. References to studies excluded in this review Exclusion no. Author. Journal (year) Title Reason of exclusion 1 Nothing A study of animal-assisted therapy and weekday placement of a social therapy Not acceptable 2 Livingston G, et al. (nothing) The effectiveness and cost-effectiveness of sensory, psychological and behavioral interventions for managing agitation in older adults with dementia Ongoing 3 Herrero P, et al. Clinical Rehabilitation (2013) Study of the therapeutic effects of a hippotherapy simulator in children with cerebral palsy: a stratified single-blind randomized controlled trial Not animal-assisted therapy 4 Cano A. (2013) Randomized control trial of an animal-assisted intervention with adjudicated youth Not detected 5 Iammateo N, et al. (2013) Animal therapy in a pediatric setting Not detected 6 Beck CE, et al. The Army Medical Department Journal (2012) The effects of animal-assisted therapy on wounded warriors in an occupational therapy life skills program Not randomized controlled trial 7 Rhodes RE, et al. Preventive Medicine (2012) Pilot study of a dog walking randomized intervention: Effects of a focus on canine exercise Not curative effect 8 Berget B, et al. Ann Ist Sanita (2011) Animal-assisted therapy with farm animals for persons with psychiatric disorders Not randomized controlled trial 9 Moretti F, et al. Psychpgeriatrics (2011) Pet therapy in elderly patients with mental illness Not randomized controlled trial 10 SilvaBorges, et al. Arq Neuropsiquiatr (2011) Therapeutic effects of a horse riding simulator in children with cerebral palsy Not animal therapy 11 Kumasaka T, et al. Journal of the Japanese Association of Rural Medicine (2010) Study of effectiveness of animal-assisted therapy for patients with mental illness in nursing support (in Japanese) Not curative effect 12 Tsai CC, et al. Anthrozoos (2010) The effect of animal-assisted therapy on stress responses in hospitalized children Not curative effect 13 Coakley AB, et al. Complementary Therapies in Clinical Practice (2009) Creating a therapeutic and healing environment with a pet therapy program Not randomized controlled trial 14 Martin C, et al. Anthrozoos (2009) Animal-assisted therapy in the treatment of substance dependence Not randomized controlled trial 15 Braun C, et al. Complementary Therapies in Clinical Practice (2009) Animal-assisted therapy as a pain relief intervention for children Not randomized controlled trial 16 LeRoux MC, et al. Jornal compilation (2009) Effect of a companion dog on depression and anxiety levels of elderly residents in a long-term care facility Not curative effect 17 Berger AM, et al. (2009) Effects of pet therapy on pain in cancer patients Not published yet 18 Toukhsati S, et al. (2009) The use of alternative therapies to treat geriatric depression Submit preparation at present dx.doi.org/10.1016/j.ctim.2013.12.016 Please cite this article in press as: Kamioka H, et al. Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials. Complement Ther Med (2014), http://dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 18 H. Kamioka et al. Appendix (Continued ) Exclusion no. Author. Journal (year) Title Reason of exclusion 19 Parish-Plass N. Clin Child Psychology and Psychiatry (2008) Animal-assisted therapy with children suffering from insecure attachment due to abuse and neglect: a method to lower the risk of intergenerational transmission of abuse? Not randomized controlled trial 20 Banks MR, et al. J Am Med Dir Assoc (2008) Animal-assisted therapy and loneliness in nursing homes: use of robotic versus living dogs Not curative effect 21 Cole KM, et al. American Journal of Critical Care (2007) Animal-assisted therapy in patients hospitalized with heart failure Reduplication 22 Prothmann A, et al. Anthrozoos (2006) Dogs in child psychotherapy: effects on state of mind Not randomized controlled trial 23 Motooka M, et al. MJA (2006) Effect of dog-walking on autonomic nervous activity in senior citizens Not curative effect 24 Colombo G, et al. Archives of Gerontology and Geriatrics (2006) Pet therapy and institutionalized elderly: A study on 144 cognitively unimpaired subjects Not curative effect 25 Anonymous (memo). Harvard Men’s Health Watch (2006) Dolphins for the doldrums? Not original article 26 Nathans-Barel I, et al. Psychother Psychosom (2005) Animal-assisted therapy ameliorates anhedonia in schizophrenia patients Not randomized controlled trial 27 Cole KM. Circulation (2005) Innovative interventions to improve management and outcomes in heart disease Not curative effect 28 Stasi MF, et al. Arch. Gerontol. Geriatr. Suppl. (2004) Pet-therapy: a trial for institutionalized frail elderly patients Not randomized controlled trial 29 Kovacs Z, et al. Clinical Rehabilitation (2004) Animal-assisted therapy for middle-aged schizophrenic patients living in a social institution. A pilot study Not randomized controlled trial 30 Bouchard F, et al. (2004) A magical dream: a pilot project in animal-assisted therapy in pediatric oncology Not original article 31 Richeson NE. American Journal of Alzheimer’s Disease and Other Domentias (2003) Effects of animal-assisted therapy on agitated behaviors and social interactions of older adults with dementia Not randomized controlled trial 32 Barker SB, et al. The Journal of ECT (2003) Effects of animal-assisted therapy on patients’ anxiety, fear, and depression before ECT Not randomized controlled trial 33 Johnson RA, et al. American Behavioral Scientist (2003) Human-animal interaction: A complementary/Alterative medical (CAM) intervention for cancer patients Not curative effect 34 Martin F, et al. Western Journal of Nursing Research (2002) Animal-assisted therapy for children with pervasive developmental disorders Not randomized controlled trial 35 Banks MR, et al. Medical sciences (2002) The effects of animal-assisted therapy on loneliness in an elderly population in long-term care facilities Not curative effect dx.doi.org/10.1016/j.ctim.2013.12.016 ARTICLE IN PRESS+ModelYCTIM-1299; No. of Pages 20 Effectiveness of animal-assisted therapy 19 Appendix (Continued ) Exclusion no. Author. Journal (year) Title Reason of exclusion 36 Kaminski M, et al. Children’s Health Care (2002) Play and pets: The physical and emotional impact of child-life and pet therapy on hospitalized children Not curative effect 37 Kanamori M, et al. American Journal of Alzheimer’s Disease and Other Domentias (2001) A day care program and evaluation of animal-assisted therapy (ATT) for the elderly with senile dementia Not randomized controlled trial 38 Kingwell BA, et al. Clinical Autonomic Research (2001) Presence of a pet dog and human cardiovascular responses to mild mental stress Not curative effect 39 Hall PL, et al. British Journal of Nursing (2000) Pets as therapy: effects on social interaction in long-stay psychiatry Not randomized controlled trial 40 Bernstein PL, et al. Anthrozoos (2000) Animal-assisted therapy enhances resident social interaction and initiation in long-term care facilities Not curative effect 41 Panzer-Koplow S, et al. Bell and Howell Information and Learning (2000) Effects of animal-assisted therapy on depression and morale among nursing home residents Not curative effect 42 Churchill M, et al. Journal of Psychosocial Nursing (1999) Using a therapy dog to alleviate the agitation and desocialization of people with Alzheimer’s disease Not randomized controlled trial 43 Hansen KM, et al. Anthrozoos (1999) Companion animals alleviating distress in children Not randomized controlled trial 44 Counsell CM. Sc. In Nursing (1997) Animal assisted therapy and the individual with spinal cord injury Not randomized controlled trial 45 Banman JK, et al. The Journal of Pastoral Care (1995) Animal-assisted therapy with adolescents in a psychiatric facility Not original article 46 Folse EB, et al. Anthrozoos (1994) Animal-assisted therapy and depression in adult college ents Not randomized controlled trial 1 1 1 1 stud References 1. Munoz Lasa S, Ferriero G, Brigatti E, Valero R, Franchignoni F. Animal-assisted interventions in internal and rehabilitation medicine: a review of the recent literature. Panminerva Med 2011;53(June (2)):129—36. 2. Hall PL, Malpus Z. Pets as therapy: effects on social interaction in long-stay psychiatry. Brit J Nurs 2000;9:2220—5. 3. American Veterinary Medical Association. Wellness guide- lines for animals in animal-assisted activity, animal-assisted therapy and resident animal programs; 2011. Available from: http://www.avma.org/KB/Policies/Pages/Wellness-Guidelines- for-Animals-in-Animal-Assisted-Activity-Animal-Assisted- Therapy-and-Resident-Animal-Programs.aspx [cited 03.08.13]. 4. Nimer J, Lundahl B. 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http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 http://refhub.elsevier.com/S0965-2299(13)00214-8/sbref0180 Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials Introduction Methods Criteria for considering studies included in this review Types of studies Types of participants Types of intervention and language Types of outcome measures Search methods for identification of studies Bibliographic database Search strategies Registry checking Handsearching, reference checking, and other Review methods Selection of trials Risk of bias (quality) assessment Summary of studies and data extraction Benefit, harm, and cost Analysis Research protocol registration Results Study selection Study characteristics Quality assessment Meta-analysis Adverse events Costs of intervention Discussion Tendency of target disease and outcome Validity of overall evidence based on quality assessment Overall evidence and quality assessment Overall evidence Future research agenda to build evidence Strength and limitations Conclusion Contributors Funding Conflict of interest statement Ethical approval Data sharing Acknowledgements Appendix References to studies excluded in this review References