The Impact of Preoperative Patient Education on Postoperative Pain, Opioid Use, and Psychological Outcomes: A Narrative Review

ABSTRACT Background Recent studies have shown that preoperative education can positively impact postoperative recovery, improving postoperative pain management and patient satisfaction. Gaps in preoperative education regarding postoperative pain and opioid use may lead to increased patient anxiety and persistent postoperative opioid use. Objectives The objective of this narrative review was to identify, examine, and summarize the available evidence on the use and effectiveness of preoperative educational interventions with respect to postoperative outcomes. Method The current narrative review focused on studies that assessed the impact of preoperative educational interventions on postoperative pain, opioid use, and psychological outcomes. The search strategy used concept blocks including “preoperative” AND “patient education” AND “elective surgery,” limited to the English language, humans, and adults, using the MEDLINE ALL database. Studies reporting on preoperative educational interventions that included postoperative outcomes were included. Studies reporting on enhanced recovery after surgery protocols were excluded. Results From a total of 761 retrieved articles, 721 were screened in full and 34 met criteria for inclusion. Of 12 studies that assessed the impact of preoperative educational interventions on postoperative pain, 5 reported a benefit for pain reduction. Eight studies examined postoperative opioid use, and all found a significant reduction in opioid consumption after preoperative education. Twenty-four studies reported on postoperative psychological outcomes, and 20 of these showed benefits of preoperative education, especially on postoperative anxiety. Conclusion Preoperative patient education interventions demonstrate promise for improving postoperative outcomes. Preoperative education programs should become a prerequisite and an available resource for all patients undergoing elective surgery.


Introduction
Acute pain after a surgical procedure is routinely treated with short-term opioid medication. 1 For many patients, however, acute pain after surgery can progress to become chronic. 2Referred to as chronic postsurgical pain, this condition has a median incidence of 20% to 30% during the 6 to 12 months after surgery. 3,4Chronic postsurgical pain can lead to reduced function and quality of life, 5,6 as well as persistent opioid use after surgery and an increased risk of opioid use disorder and overdose. 7,83][14] This narrative review provides an overview of the available evidence on the use and effectiveness of preoperative education to inform future interventions aimed at improving postoperative pain management and safe opioid use.

Prescription Opioid Use and the Opioid Epidemic
According to the Canadian Medical Protection Association, more than 1 million surgical procedures are performed annually in Canada. 15Opioids are a class of powerful analgesic medications that are routinely prescribed for postoperative pain management, and surgery remains the most common indication for opioid initiation. 1 However, the persistent use of prescription opioids after surgery can lead to opioid use disorder and has been considered as a contributing factor to the ongoing opioid crisis. 16,17According to the Centers for Disease Control and Prevention, having a history of a prescription for an opioid pain medication increases the risk of overdose and opioid use disorder. 18Similarly, excessive postoperative opioid use increases the risk of drug diversion and the development of persistent opioid use with the possibility of developing an opioid use disorder and overdose. 1,17ioid overdose continues to be a major cause of mortality in Canada.According to Health Canada, there were a total of 36,442 apparent opioid toxicity deaths between January 2016 and December 2022. 19Between 2016 and 2018, more than 9000 Canadians died from apparent opioid-related harms. 20Though most deaths have been due to illicit opioid use, prescription opioids continue to be a focus for public health reform 21 because chronic opioid treatment has been linked to increased likelihood of illicit drug use. 22,23For instance, in a sample of individuals in British Columbia who experienced an overdose between 2015 and 2016, around half of the sample had been prescribed opioids for pain in the previous 5 years, but most did not have an active opioid prescription at the time of overdose. 23Addressing persistent pain after surgery and related persistent opioid use is an important avenue to reducing later problematic opioid use.

Initiatives to Minimize Postoperative Opioid Consumption
The Canadian Institute for Health Information stated that in 2018 almost one in eight people in the study population were prescribed opioids. 21In Canada, consumption of prescription opioids increased 202.8% between 2001 to 2009, with a further 6.4% increase observed from 2010 to 2015. 21In light of this considerable increase, the Canadian physician community responded by reducing opioid prescribing.In subsequent years, from 2013 to 2018, the proportion of people prescribed opioids decreased from 14.3% to 12.3%, representing an overall 8% decrease in the number of persons taking opioids. 21ther initiatives have also been established to minimize postoperative opioid consumption and misuse, including evidence-based prescribing guidelines. 24The higher the opioid dose, the higher the risk for misuse and overdose 25 and the lower the likelihood that a patient is able to wean from their opioid medication postdischarge. 26These risks further increase in patients with an active or prior substance use disorder and concurrent psychological diagnoses. 26here is evidence to suggest that an overdose risk exists at doses as low as <20 mg morphine equivalents daily (MED). 27A significant increase in overdose risk occurs if patients consume greater than 50 mg MED. 28Current guidelines regarding safe opioid prescribing practices suggest that patients commencing opioid therapy be restricted to <50 MED, with the maximum prescribed dose to <90 MED. 27However, in the perioperative setting, patients are often discharged with doses exceeding these recommendations. 26In addition to prescribing guidelines, programs that can decrease the use of postoperative opioids by educating patients about the potential pitfalls could help reduce postdischarge morbidity and overdose risk related to opioid use.

Benefits of Patient Education for Postoperative Recovery
Multidisciplinary strategies that focus on opioid-sparing multimodal analgesic regimens, such as enhanced recovery after surgery programs, have been associated with decreased perioperative opioid consumption. 113][14] Preoperative educational interventions have been successfully implemented to help decrease postoperative pain, 29 opioid use, 30 and perioperative anxiety. 31The objective of this narrative review was to identify, examine, and summarize the available evidence on the use and effectiveness of preoperative educational interventions with respect to their impact on pain, opioid use, and psychological outcomes.The findings from this review will ultimately allow us to make more informed decisions regarding the most suitable types of preoperative educational tools and enable the creation of novel tools to improve patient recovery and functioning following surgery.

Methods
Team members ran a MEDLINE ALL (Ovid Platform) database search from its inception (1946-May 24, 2022).The search strategy concept blocks were assembled on the topics of "preoperative" AND "patient education" AND "elective surgery," limited to the English language, humans, and adults.Preliminary searches were performed and fulltext literature was examined for keywords, controlled vocabularies, text word terms, and synonyms.
In total, the search yielded 761 citations after duplicates were accounted for (Figure 1).Titles and abstracts of identified studies were screened by two reviewers (H.Y. and P. J.).The full texts of eligible studies were retrieved and screened independently.If agreement could not be reached on whether a study should be included or excluded, a third reviewer (H.C.) reviewed the manuscript and made the final decision to include or exclude the study.Studies reporting on the impact of preoperative educational interventions on pain, and/or opioid use, and/or psychological outcomes were included.Studies were excluded if they reported on enhanced recovery after surgery protocols.
An extraction table was used to collect relevant data from each included study.Each entry included the title, type of study, sample size, intervention, and relevant findings.The results were subdivided into categories relevant to postsurgical outcomes of interest.The methodological quality of each study was also assessed.The Cochrane Risk of Bias v2 tool 32 was used to assess randomized controlled trials and the Risk of Bias in Non-Randomized Studies of Interventions tool 33 was used to assess nonrandomized prospective studies.

Overview of Articles
Thirty-three of the included studies were randomized controlled trials and one was a prospective controlled trial.Twelve studies examined the impact of preoperative educational interventions on postoperative pain, 8 examined the impact of preoperative educational interventions on postoperative opioid use, and 24 studies evaluated postoperative psychological outcomes.Details of the included studies are summarized in Table 1.

Methodological Quality
9][60][61][62][63] The one nonrandomized prospective study had a moderate risk of bias. 64he most common area of concern in study design was due to bias arising from the randomization process.Potential for bias in selection of the reported result was also common because many studies did not report information regarding preregistration of the study protocol.

Preoperative Interventions
Multimedia resources were the most common format for delivering preoperative education among the included studies.Informational videos were most frequently used, with ten studies that used videos only, 31,34,38,42,43,46,54,58,59,64 three that combined videos and paper resources, 30,36,45 two that combined video with in-person education, 35,57 and one that used video, paper, and in-person education. 47Four studies 40,44,51,60 delivered educational interventions using interactive web applications, three of which included videos 44,51,60 and one that featured a social media interface for interactions with health care providers. 60Two studies used audio-based resources. 48,63ix studies implemented in-person education only - 37,39,41,52,61,62 and another five added paper resources to in-person education, 29,49,50,53,56 including brochures, booklets, and information cards, with one of these studies also including follow-up phone calls. 29Only one study relied solely on a paper resource. 55In-person education was typically delivered by a healthcare provider, including nursing staff, 29,35,41,47,52,53,61 physicians (e.g., anesthesiologists, surgeons), 35,39,49,50,56 a physiotherapist, 37 and a music therapist. 63Two studies used a patient-centered technique, - 49,52 providing patients with the information necessary to participate in medical decision making.In one study the interventional group had a tour of the operating theater prior to surgery. 39Two studies used comfort therapy as an intervention, including one that used meditation 62 and another that used music therapy. 63One study used hypnosis in the form of guided imagery, 48 one used psychosocial therapy/counseling, 50 and another used goal attainment and physiotherapy 37

Postoperative Pain
7][58]60 Five of these studies 29,47,50,52,55,56 found a significant reduction in postoperative pain after preoperative education, and all involved in-person interaction with a health care provider.Sawhney et al. 29 evaluated the effectiveness of an individualized hernia repair education intervention for patients undergoing inguinal hernia repair.The hernia repair education intervention included written and verbal information delivered by a nurse regarding managing pain as well as two telephone support calls.At day 2, the intervention group reported significantly lower scores across pain intensity outcomes, including worst 24-h pain on movement and at rest, and pain now on movement and at rest, in comparison to the control group.Pereira et al. 52 also examined the benefits of nurse-led empathic patient-centered education in patients undergoing ambulatory surgery.They found that the intervention group had lower pain levels on the second postoperative day compared to the control group.
In a study by Sugai et al., 56 a surgeon delivered inperson education and reviewed a written handout with patients 2 weeks before outpatient surgery.The topic of education consisted of information about how the body responds to pain and how endorphins cause natural analgesia.The intervention group had significantly lower average pain scores than the control group and a shorter duration of pain. Lee et al. 47 employed an educational intervention in patients undergoing spinal surgery involving an in-depth booklet and videos on topics related to the disease, surgery, and postoperative care.A surgeon also reviewed the content in person with patients.The study found that pain levels were significantly lower for the interventional arm of the study compared to standard care.
Schmidt et al. 55 also delivered preoperative education using a patient empowerment information booklet with in-depth information regarding surgery, anesthesia, pain management, and rehabilitation.Patients were aged 65 and older and undergoing elective surgery for gastrointestinal, genitourinary, and thoracic cancer.In addition to receiving the booklet, patients were also asked to keep a diary and repeatedly encouraged to consult with the health care team regarding medication and rehabilitation.Patients in the intervention group reported significantly less postoperative pain than the control group that received standard care.
Four studies found no effect of preoperative education on postoperative pain, 43,50,57,58 and one study reported mixed results. 40Three of the studies that found no effect used videos as the educational intervention. 43,57,58incent et al. 43 employed a 5-min video to deliver information about safe opioid use and nonopioid pain management to patients undergoing upper extremity surgery.They found no differences in pain scores between the education and the control groups.Similarly, Ilyas et al. 58 used a brief video to deliver education on the same topics to patients undergoing outpatient orthopedic surgery.They also found no significant effects on the experience of pain between the intervention and control groups.Campagna et al. 57 also employed a video of unspecified length to deliver information regarding the perioperative experience.In addition, they gave patients an opportunity to ask questions about any doubts they had regarding the content of the video.They reported that postoperative pain was well controlled among female surgical patients presenting for colorectal surgery secondary to gastrointestinal cancer and that there were no differences found in postoperative pain in the education group compared to the control group.
A study by Alter and Ilyas 50 did not use a video but instead examined the benefits of surgeon-delivered education alongside a paper handout on the topic of opioid use and pain management in patients undergoing carpal tunnel release surgery.They found no significant differences in pain levels between the intervention and control groups.Strøm et al. 40 employed an interactive web platform to deliver education and found no improvement in pain at 3 months and 6 months after lumbar spine fusion surgery, but they did observe improved pain at 2 days after surgery.
Importantly, three of the above studies that found no effect on pain also examined opioid use following the educational intervention, and all found a decrease in postoperative opioid consumption (see below in Postoperative Opioid Use). 43,50,58These findings demonstrate that pain levels were not affected despite patients using less opioid medication postoperatively.
Two studies found an increase in reported postoperative pain following preoperative educational interventions.Peng et al. 60 found that preoperative education using an anesthesia service platform was effective in preventing anxiety in female patients before laparoscopic cholecystectomy, including improving patients' general well-being and shortening their length of stay, but patients undergoing the intervention reported higher postoperative pain levels.Klaiber et al. 41 found mixed results following a 1-h nurse-led seminar on preventing postoperative complications and coping strategies for pain.In a cluster-randomized trial, patients undergoing major visceral surgery who received education had comparable pain scores to control patients on postoperative days 2 and 7, except patients in the education group reported higher scores with respect to pain intensity on day 7.The above studies highlight that some negative effects with respect to the experience of postoperative pain following educational interventions can occur.

Postoperative Opioid Use
A total of eight studies reported on postoperative opioid consumption. 30,36,43,45,50,56,58,59All of these found that perioperative patient education significantly reduced postoperative opioid use.Six studies employed videos about safe opioid use as the educational intervention. 30,36,43,45,58,59In a study by Vincent et al. 43 of patients undergoing outpatient upper extremity surgery, patients who received preoperative opioid counseling in the form of a 5-min video consumed significantly fewer opioids postoperatively, 93.7 morphine equivalent units compared to 143.4 morphine equivalent units in the control group.There was no difference in pain at any point between groups.In a study by Stepan et al., 36 all patients scheduled to undergo ambulatory hand surgery received a webinar video with instructions for study participation, and the education group received an additional 10 min of instruction on postoperative pain management plus a postoperative pain management reference card.Patients in the education group were more likely to take no opioid medication (42% versus 25%) and took significantly fewer opioid pills than those in the control group.Zohar-Bondar et al. 30 randomized patients scheduled to undergo elective outpatient surgery, comprising soft tissue procedures distal to the wrist, to either receive pain management education or standard of care.As in Stepan et al., 36 all patients viewed a webinar video before surgery, with the education group having an additional 10 min of education and receiving a pain management reference card for review after surgery.Patients in the education group took significantly fewer opioid pills (median = 0, range 0-13) than those in the standard group (median = 0.5, range 0-40), although opioid consumption was low in both groups likely due to the minor nature of the surgical procedure.
In a study by Paskey et al., 59 preoperative opioid counseling was delivered via a 5-min video.Patients undergoing elective outpatient lower extremity orthopedic surgery who received the preoperative opioid counseling consumed on average 6.5 opioid pills in comparison to the control group, which consumed on average 12.4 pills.In a study by Ilyas et al., 58 patients undergoing outpatient orthopedic surgeries who also received preoperative opioid education in the form of a brief video consumed significantly fewer opioids (6 pills) when compared with the group not receiving education (12 pills).This finding was consistent across both upper and lower extremity surgery.
A study by Cheesman et al. 45 examined the long-term effects of preoperative opioid education delivered in the form of a 2-min video and a paper outline of the key points in the video.They examined postoperative opioid consumption after arthroscopic rotator cuff repair at 2-year follow-up.They found that preoperative opioid education had significant benefits for patients in the education cohort compared to the control cohort, including a lower rate of opioid dependence, fewer filled prescriptions for opioids, and lower consumption of opioids.
In two studies, preoperative opioid education was delivered in person by a surgeon. 50,56A study by Alter and Ilyas provided in-person counseling and a one-page information form regarding opioid use and nonopioid therapy options. 35They found that patients in the counseling group consumed significantly fewer opioid pills and fewer total pain pills compared to control patients, with no significant difference in reported pain levels.Similarly, in a study by Sugai et al., 56 participants in the experimental group received in-person and written forms of patient education 2 weeks before outpatient surgery consisting of information about how the body responds to pain and how endorphins cause natural analgesia.Ninety percent of subjects in the experimental group declined a prescription for hydrocodone, whereas 100% of participants in the control group filled their hydrocodone prescriptions.However, the study did not specify whether the control group was given the option to decline the hydrocodone prescription in the same way that the experimental group was.Importantly, the study also did not provide information on how much hydrocodone was consumed by control participants, and only 20% requested a refill of hydrocodone.There was also little information provided regarding the types of surgeries performed and how they were distributed between the two groups.The control group was also younger than the experimental group, which may have confounded the results because younger age is a known risk factor for opioid use after surgery. 65
Fahimi et al. 34 observed a reduction in postoperative delirium following a preoperative educational intervention to help patients undergoing coronary artery bypass surgery familiarize themselves with the surgical and intensive care unit (ICU) environment and procedures.The authors postulated that increased familiarity with the ICU resulting from the preoperative intervention contributed to a lower incidence of delirium on days 2 to 4 after surgery.Billquist et al. 48found improved patient preparedness after preoperative education.
In three studies, 40,42,57 no differences were found in postoperative psychological outcomes after preoperative education.Strøm et al. 40 examined the effect of a webbased Spine Platform featuring Interaction and Information by Animation on symptoms of anxiety, depression, pain, disability, and health-related quality of life.They found no statistically significant difference between the web-based Spine Platform featuring Interaction and Information by Animation group and the control group regarding Hospital Anxiety and Depression Scale scores at 3-month follow-up.Similarly, Eley et al. 42 and Campagna et al. 57 found no effect of education on postoperative anxiety.Eley et al. also saw no improvement in satisfaction following preoperative education for women undergoing elective cesarean section and observed that satisfaction was already high in this study population.
Klaiber et al. 41 found mixed effects for psychological outcomes.Anxiety levels on day 7 and day 30 after surgery did not differ in patients undergoing major visceral surgery, whether they were provided with preoperative education or not.However, they did observe lower depression scores on day 30 in the group that received education compared to standard care.

Discussion
Overall, this narrative review found that preoperative education interventions are beneficial in reducing postsurgical opioid consumption and improving psychological outcomes, especially anxiety.There is also evidence of benefits for postoperative pain, but studies are more mixed in this regard.Preoperative educational interventions are effective strategies that can be used to enhance patient safety and overall psychological well-being.
Five of 12 studies that examined effects on pain reported a reduction in postoperative pain after integrating perioperative education, 29,47,50,52,55,56 while four studies found no effect on pain, 43,50,57,58 one study found mixed effects, 40 and two studies found evidence for a negative effect. 41,60Studies that showed a benefit of educational interventions for postoperative pain relied primarily on in-person delivery of education, as opposed to video-based interventions or web applications primarily used in the other studies.Controlled studies that more carefully examine how the format of preoperative education influences postoperative pain are therefore warranted to find the best protocol for improving this outcome.
All studies that evaluated postoperative opioid consumption found that perioperative education significantly reduced postoperative opioid use without adverse effects on postoperative pain. 30,36,43,45,50,56,58,59ll of these studies focused the topic of education on safe postoperative opioid use and nonopioid approaches to pain management, and most relied on brief videos to deliver the educational intervention.These findings demonstrate that preoperative opioid education is feasible and effective in reducing subsequent opioid use, providing a promising avenue toward minimizing postoperative opioid consumption.
Psychological outcomes were by far the most common outcome reported (i.e., 24 articles), with significant improvements noted with respect to anxiety 31,35,38,39,44,46,[52][53][54][60][61][62][63][64] and patient satisfaction - 35,37,39,49,51,52,54 across many of the studies. Therewas no one approach to the format and topic of education that stood out at as superior in this domain, suggesting that there is flexibility in selecting the appropriate educational approach to implement preoperatively based on the available resources and constraints of the surgical service.
Most of the studies included in this review relied on short educational interventions that were practical to implement as part of the process of preparing patients for surgery.There was some evidence that in-person interventions delivered by a health care provider were more effective for improving postoperative pain, whereas using a brief educational video was sufficient to have a positive impact on reducing postoperative opioid consumption.Out of 34 studies, only 2 showed no effect of the education intervention in any domain.These findings suggest that implementing a preoperative educational intervention as part of routine preoperative care is feasible and has a high probability of success.

Limitations
Although MEDLINE ALL is a very robust database, we may not have identified all articles available on the topic by searching only this database.This narrative review was limited to studies that met the current inclusion criteria.
Among the included studies, the length of follow-up was variable, and there were limited data regarding longterm benefit.Only four studies measured outcomes beyond the first 3 months after surgery, 37,40,45,55 with two studies finding that preoperative educational interventions had long-term benefits at 12 months 37 and up to 2 years 45 and the other two finding no differences in outcomes at 6 months 40 and 12 months. 55Orthopedics was the most common surgical specialty represented among the included studies, which may limit the overall applicability of the results.In some studies, clinical details, such as patient demographic characteristics, history of chronic pain, and type of opioid prescribed were not available.
There were also concerns regarding the methodological quality of two-thirds of the included studies.Many studies provided limited details regarding the randomization and concealment process or used approaches that did not reflect assignment at random (e.g., assignment by year of birth).Proper blinding of participants and health care providers was also a notable challenge with study design across many of the include studies.Participants and health care providers were often aware of the participants' assigned condition by virtue of implementing the educational intervention.Only a few studies took care to design an intervention that appeared similar in both the experimental and control groups.For instance, Stepan et al. 36 and Zohar-Bondar et al. 30 used a video intervention where both groups watched a video about study participation but the intervention group also received education as part of the video content.This approach allowed for more careful assessment of the influence of educational content itself and proper blinding.
Overall, more rigorous methodological approaches are required in future research in this area.

Future Directions
Opioids have played an integral role in treating acute postoperative pain, and surgery remains one of the most common indications for the initiation of opioids. 1 Prescribing habits vary worldwide, with North American surgeons out-prescribing other parts of the world, 66 and Canada ranking second in the number of opioids prescriptions per capita. 21Thus, opioid prescribing has remained a prominent public health concern and a contributing factor to the ongoing opioid epidemic.Perioperatively, physicians have responded to this crisis by creating new opioid prescribing guidelines. 24Organizations, including the Centers for Disease Control and Prevention, have continued to support health care systems with data, tools, and guidance for evidence-based decision making with aims to improve opioid prescribing and patient safety.A part of this initiative includes increasing public awareness about prescription opioids to encourage safe choices regarding opioid consumption. 67The preoperative period is a pivotal time point to initiate patient education and promote greater awareness of opioid safety.
As we continue to perform millions of major surgical interventions annually, it behooves perioperative health care practitioners to create perioperative education resources.The cost to society for poor surgical outcomes is estimated to be billions of dollars per year. 68Every attempt should be made to create low-cost solutions to such a major health care challenge.There is currently considerable interest in building transitional pain services that are focused on identifying and treating patients at risk of developing chronic postsurgical pain and persistent opioid use. 9The results of this review suggest that presurgical educational tools could be a useful addition to these types of services and provide value for patients set to undergo a surgical intervention.
A strategy that provides essential information to patients about their surgical journey, including postoperative pain and safe opioid use, and helps to allay patients' anxiety and fears prior to surgery would pay dividends going forward.Ultimately, a nationally available preoperative educational resource would have a beneficial impact on reducing pain-related disability and persistent opioid use in surgical patients across Canada.
The multistakeholder national initiative, Pain Canada, supported by Pain BC, aims to develop preoperative education modules that can be accessible to all Canadians scheduled to have surgery.We hope that these online modules will help to prepare patients psychologically and provide them with information about what to expect during the preoperative and postoperative periods.Delivering this type of educational content will aim to foster clearer expectations regarding the postsurgical recovery process and safe medication use.

Conclusion
It is imperative that strategies continue to be implemented to reduce persistent opioid use following surgery, which could evolve into an opioid use disorder for some patients.Preoperative educational programs continue to show promise as an effective strategy aimed at protecting patients and improving healthcare in Canada.Though there are no concrete protocols that can be outlined from this narrative review, it is apparent that preoperative education can be consistently successful in helping to reduce opioid use and improve psychological outcomes, as well as having potential for improving postoperative pain.Future research is needed, aligned with novel educational content delivered in a timely manner in the preoperative setting.Based on this review, we would anticipate that these educational interventions will improve outcomes, positively impact patient psychological outcomes, reduce health care costs, and ultimately save lives.

Disclosure Statement
HC is funded via a Merit Award from the Department of Anesthesiology and Pain Medicine at the University of Toronto and is the president-elect of the Canadian Pain Society.BR was funded by a CIHR Banting Postdoctoral Fellowship.All other authors have no conflict of interest to report.

Figure 1 .
Figure 1.Flow diagram of included articles.

Table 1 .
Summary of relevant details of each included study.
RCT: randomized control trial; OR: operating room; ICU: intensive care unit; POD: post-operative day

Table 2 .
Risk of bias assessment using the Cochrane Risk of Bias v2 tool for randomized trials.

Table 3 .
Risk of bias assessment using the Risk of Bias in Non-randomized Studies of Interventions tool.