The potential for diversion of prescribed opioids among orthopaedic patients: Results of an anonymous patient survey.

INTRODUCTION: Diversion of prescription opioid medication is a contributor to the opioid epidemic. Safe handling practices can reduce the risk of diversion. We aimed to understand: 1) if orthopaedic patients received instructions on how to safely handle opioids, 2) their typical storage/disposal practices, and 3) their willingness to participate in an opioid disposal program (ODP).
METHODS: Cross-sectional study of adult orthopaedic patients who completed an anonymous survey on current or past prescription opioid use, instruction on handling, storage and disposal practices, presence of children in the household, and willingness to participate in an ODP. Frequencies and percentages of responses were computed, both overall and stratified by possession of unused opioids.
RESULTS: 569 respondents who reported either current or past prescription opioid use were analyzed. 44% reported receiving storage instructions and 56% reported receiving disposal instructions from a health care provider. Many respondents indicated unsafe handling practices: possessing unused opioids (34%), using unsafe storage methods (90%), and using unsafe disposal methods (34%). Respondents with unused opioids were less likely to report receiving handling instructions or using safe handling methods, and 47% of this group reported having minors or young adults in the household. Respondents who received storage and disposal instructions were more likely to report safe storage and disposal methods. Seventy-four percent of respondents reported that they would participate in an ODP.
CONCLUSION: While many orthopaedic patients report inadequate education on safe opioid handling and using unsafe handling practices, findings suggest targeted education is associated with better behaviours. However, patients are willing to safely dispose of unused medication if provided a convenient option. These findings suggest a need to address patient knowledge and behavior regarding opioid handling to reduce the risk of opioid diversion.

Introduction

The opioid epidemic is a critical public health issue in Canada [1]. Opioid-related hospitalizations and rates of opioid poisoning emergency department (ED) visits continue to increase [2]. Rates of hospitalization for opioid poisoning are growing among youth (age 15 to 24) and younger adults (age 25 to 44), with respective increases of 53% and 62% from 2013 to 2017 [3]. In 2019, one in ten Ontario students in intermediate or secondary school reported using prescription opioids not prescribed to them, with the majority reporting that they obtained these drugs from their home [4]. However, opioid diversion in the household has received little attention from the medical community despite it being a significant source of opioid misuse in this vulnerable group.

Opioids are commonly prescribed for musculoskeletal pain and post-surgical pain [5-7]. Among physicians, orthopaedic surgeons are the third highest group of opioid prescribers [8,9]. Consequently, orthopaedic surgery patients may be important contributors to opioid diversion, as the majority of surgical patients use less than half of their prescribed opioid medication and often keep the surplus [8,9]. While current efforts to address over-prescription of opioids are a critical step towards reduction of opioid diversion [10,11], little is known about how opioid handling in the household may relate to diversion. The primary objectives of this study were to develop a better understanding of: 1) whether orthopaedic patients receive instruction on how to safely handle opioids, 2) their typical storage and disposal practices, and 3) their willingness to participate in a hypothetical hospital-based opioid disposal program. Secondarily, we examined how these factors varied among patients with and without unused opioids at home, and whether patient responses varied with the presence of children or young adults in the home.

Materials and methods

Study design

Cross-sectional study of consecutive patients who visited the outpatient orthopaedic clinic at Toronto Western Hospital from May to July 2017. Patients were invited to complete and return an anonymous paper survey to an unmanned box in the clinic. Respondents who reported current or former use of opioids were included in the analysis sample.

Data collection

The survey collected respondents’ sex, age group, history of being prescribed opioids, previous instruction regarding safe opioid handling practices, actual handling practices, and the presence of children and/or young adults in their household (see S1 Appendix). Survey items were generated based on review of existing studies and Canadian recommendations [12,13].

Survey measures

Opioid use

Respondents were asked if they had ever been prescribed opioid/narcotic pain medications (options: never; prescribed in the past but not currently using; currently using sometimes but not daily; currently using daily). This question was not limited to prescription by an orthopaedic surgeon.

Unused opioids at home

Respondents were asked if they had any opioids at home that were no longer being used or were expired (“Yes, prescribed to me”, “Yes, prescribed to someone else”, or “No”). Respondents reporting any unused opioids at home were collapsed into one group.

Minors and/or young adults in the home

Respondents were asked if children, teenagers, or young adults lived in or visited their home (“No”, “Yes, young children aged 0–6 years”, “Yes, older children aged 7–12 years”, “Yes, teenagers aged 13–17 years”, and/or “Yes, young adults aged 18–25 years”).

Instruction regarding safe opioid storage/disposal

Respondents who had been prescribed opioids were asked if they had ever received information on how to a) store and b) dispose of opioids (“Yes, from a pharmacist”, “Yes, from a healthcare provider”, “Yes, from another source”, “No, I have never received such information”, and/or “I don’t know”). Appropriate instruction was defined as receiving the information from a pharmacist or health care provider.

Opioid storage

Respondents were asked how they typically stored opioids in their home (“Cabinet/storage with a latch”, “Cabinet/storage with a lock”, “Cabinet/storage with no latch or lock”, or “Other”). Canadian guidelines state that opioids should be stored “out of sight and reach of children and pets” and “in a safe place to prevent theft, problematic use or accidental exposure” [12]. For this analysis, locked opioid storage locations were considered secure, in accordance with existing studies [14-17].

Opioid disposal

Respondents were asked how they typically disposed of opioids (“Flush down the toilet or sink”, “Throw away in garbage”, “Mix with undesirable material [e.g. kitty litter, coffee grounds] and throw in garbage”, “Return to a pharmacy or community take-back program”, “I would not dispose of it”, and/or “Other”). Safe opioid disposal was defined in accordance with Canadian guidelines13 as either a) returning unused opioids to a pharmacy or community take-back program, or b) mixing the medication with undesirable material and throwing it in the garbage.

Sharing opioid medication

Respondents were asked if they had ever shared opioids with another person (“Yes, I have shared opioid/narcotic medication prescribed to me”, “Yes, I have used opioid/narcotic medication prescribed to someone else”, and/or “No”).

Participation in a hospital-based take-back program

Respondents were asked if they would be willing to safely dispose of unused opioid medication (given that they had any) at their next hospital appointment (“Yes” or “No”). Respondents who were not willing to participate were asked to specify their reason(s), with options: “I am afraid my pain will come back and I’m not willing to be without it”, “If I need it again, I will not be able to get it from a doctor in a timely manner”, “I do not want to throw it away because I paid for it”, “My friends or family members may need it”, “I would prefer to dispose of it myself”, and/or “Other”.

Statistical analysis

Responses were summarized with frequencies and percentages, both in the full sample and stratified by presence of unused opioid medication in the home. Respondents who reported any unused opioids at home were compared to respondents with no unused opioids using chi-square independence tests. Confidence intervals for differences in proportions were also calculated using the Agresti and Coull method [18], with Bonferroni adjustment to control family-wise error when necessary [19]. A descriptive comparison of reported opioid storage method versus presence of children, teenagers, and/or young adults in the home versus was also performed. After confirming that all survey items had a completion rate of at least 90%, missing responses were removed using pairwise deletion.

Ethics approval

This study was approved by the University Health Network Research Ethics Board (approval number 19–5808) as a retrospective analysis of data collected anonymously for a clinical quality initiative. Since identifying information was not collected, the informed consent requirement was waived.

Results

Of 784 total respondents, 569 who indicated that they had been prescribed opioid medication in the past were included in the analysis sample. The remaining respondents either reported that they had never been prescribed opioids (n = 182) or did not indicate their use of opioids (n = 33). Sixty percent of the sample were women, and 58% were age 55 or older (Table 1). Seventy-two percent were former opioid users and 28% were current users. Forty-two percent reported at least one child, teenager, or young adult living in or visiting their home. Overall, 34% of respondents reported having unused opioids at home. Having unused opioids at home was not significantly related to age group, gender, or having minors/young adults at home, but was more common among former versus current opioid users (p<0.001).

Table 1

Characteristics of opioid-using respondents, overall and by presence of unused opioids at home.

			Unused opioid medication at home
Measure	Category	All opioid ever-users, % (count) N = 569	No unused opioids, % (count) N = 374	Any unused opioids, % (count) N = 195	Difference [95% CI]	P
Age groupa,b	18–24	3.9% (22)	3.5% (13)	4.6% (9)	1.1% [-3.5, 6.2]	0.316
	25–34	11.1% (63)	10.2% (38)	12.8% (25)	2.6% [-4.8, 10.4]
	35–44	10.7% (61)	11.8% (44)	8.7% (17)	-3.1% [-9.9, 4.1]
	45–54	16.7% (95)	16.9% (63)	16.4% (32)	-0.5% [-9.0, 8.4]
	55–64	27.8% (158)	29.5% (110)	24.6% (48)	-4.9% [-15.0, 5.5]
	65–74	21.1% (120)	18.8% (70)	25.6% (50)	6.9% [-2.9, 16.8]
	75+	8.6% (49)	9.4% (35)	7.2% (14)	-2.2% [-8.4, 4.4]
	Age group not reported	— (1)	— (1)	— (0)
Female sexa	—	59.6% (334)	58.9% (216)	61.1% (118)	2.3% [-6.3, 10.7]	0.665
	Sex not reported	— (9)	— (7)	— (2)
Prescription opioid medication useb	Former	71.5% (407)	65.2% (244)	83.6% (163)	18.3% [10.0, 26.2]	<0.001*
	Sometimes	11.8% (67)	14.4% (54)	6.7% (13)	-7.8% [-13.3, -1.7]
	Daily	16.7% (95)	20.3% (76)	9.7% (19)	-10.6% [-17.0, -3.6]
Do children, teenagers, or young adults live in your home or visit your home?c	Young children (age 0–6)	12.3% (70)	10.7% (40)	15.4% (30)	4.7% [-1.2, 10.8]	0.138
	Older children (age 7–12)	13.5% (77)	14.4% (54)	11.8% (23)	-2.6% [-8.2, 3.4]	0.456
	Teenagers (age 13–17)	12.0% (68)	9.9% (37)	15.9% (31)	6.0% [0.2, 12.1]	0.050
	Young adults (age 18–25)	20.7% (118)	19.8% (74)	22.6% (44)	2.8% [-4.2, 10.0]	0.505
	None of the above	58.3% (332)	61.2% (229)	52.8% (103)	-8.4% [-16.9, 0.2]	0.066

CI = confidence interval.

* P < 0.05 (chi-square test of independence: No unused opioids versus any unused opioids).

a Percentages calculated excluding missing responses.

b Confidence intervals adjusted using Bonferroni correction to control familywise error.

c Multiple selections were permitted; percentages may total more than 100%.

Fewer than half of respondents reported that they received appropriate instruction in opioid medication handling: 43% received storage instructions and 37% received disposal instructions from a pharmacist or other healthcare provider (HCP) (Table 2). Many respondents stated that they received no storage (37%) or disposal (43%) instructions. Compared to respondents who reported no unused opioids at home, those who did have unused opioids were significantly less likely to have received storage instructions (36% vs. 46%, p = 0.035) or disposal instructions (27% vs. 43%, p<0.001) from a pharmacist or other HCP.

Table 2

Opioid handling information sources and behaviours, overall and by presence of unused opioids at home.

			Unused opioid medication at home
Measure	Category	All opioid ever-users, % (count) N = 569	No unused opioids, % (count) N = 374	Any unused opioids, % (count) N = 195	Difference [95% CI]	P
Guidance on safe storage of opioids
Opioid storage information source(s)c	Pharmacist	35.5% (202)	37.7% (141)	31.3% (61)	-6.4% [-14.4, 1.8]	0.154
	Other healthcare provider	13.4% (76)	15.8% (59)	8.7% (17)	-7.1% [-12.3, -1.4]	0.026*
	Another source	3.2% (18)	4.0% (15)	1.5% (3)	-2.5% [-5.1, 0.6]	0.178
	I have never received this information	37.3% (212)	32.4% (121)	46.7% (91)	14.3% [5.8, 22.7]	0.001*
	I don’t recall	15.3% (87)	15.5% (58)	14.9% (29)	-0.6% [-6.7, 5.8]	0.938
Received storage information from a pharmacist or other healthcare provider	—	42.7% (243)	46.0% (172)	36.4% (71)	-9.6% [-17.9, -1.1]	0.035*
Guidance on safe disposal of opioids
Opioid disposal information source(s)c	Pharmacist	33.2% (189)	38.2% (143)	23.6% (46)	-14.6% [-22.2, -6.7]	<0.001*
	Other healthcare provider	8.4% (48)	9.6% (36)	6.2% (12)	-3.5% [-7.8, 1.4]	0.209
	Another source	7.6% (43)	8.6% (32)	5.6% (11)	-2.9% [-7.1, 1.7]	0.279
	I have never received this information	42.9% (244)	34.8% (130)	58.5% (114)	23.7% [15.1, 31.9]	<0.001*
	I don’t recall	11.4% (65)	12.3% (46)	9.7% (19)	-2.6% [-7.7, 3.0]	0.441
Received disposal information from a pharmacist or other healthcare provider	—	37.4% (213)	42.8% (160)	27.2% (53)	-15.6% [-23.4, -7.4]	<0.001*
Opioid handling behaviors
Do you have any opioid medication in your household that is no longer being used or is expired?c	Yes, medication prescribed to me	30.6% (174)	—	89.2% (174)	—	—
	Yes, medication prescribed to someone else	5.8% (33)	—	16.9% (33)	—
How do you store opioid/narcotic medication in your household?a	Locked storage	9.8% (52)	13.4% (45)	3.7% (7)	-9.7% [-14.0, -4.8]	<0.001*
	Unlocked storage	90.2% (476)	86.6% (292)	96.3% (184)	9.7% [4.8, 14.0]
How do you dispose of your unused opioid medication?c	Flush down the sink or toilet	7.9% (45)	8.8% (33)	6.2% (12)	-2.7% [-7.0, 2.1]	0.339
	Throw away in garbage	15.5% (88)	11.8% (44)	22.6% (44)	10.8% [4.2, 17.6]	0.001*
	Mix with undesirable material (e.g. kitty litter, coffee grounds) and throw in garbage	1.8% (10)	2.1% (8)	1.0% (2)	-1.1% [-3.2, 1.4]	0.533
	Return it to the pharmacy or a community take-back program	54.1% (308)	56.7% (212)	49.2% (96)	-7.5% [-16.0, 1.2]	0.109
	I would not dispose of it	13.5% (77)	9.9% (37)	20.5% (40)	10.6% [4.3, 17.1]	<0.001*
	Other method	5.4% (31)	4.8% (18)	6.7% (13)	1.9% [-2.2, 6.3]	0.465
Respondent reported a safe disposal method	—	55.5% (316)	58.3% (218)	50.3% (98)	-8.0% [-16.6, 0.6]	0.082
Have you ever shared prescription opioid/narcotic medication with another person?b	Yes, I have shared medication prescribed to me	4.6% (26)	3.2% (12)	7.2% (14)	4.0% [-0.9, 9.2]	<0.001*
	Yes, I have used medication prescribed to someone else	2.1% (12)	1.1% (4)	4.1% (8)	3.0% [-0.6, 7.1]
	Yes, I have both shared medication prescribed to me and used medication prescribed to someone else	1.1% (6)	0.3% (1)	2.6% (5)	2.3% [-0.6, 5.6]
	No	92.3% (525)	95.5% (357)	86.2% (168)	-9.3% [-15.9, -2.9]
If you had unused opioid/narcotic medication, would you be willing to bring it to your next appointment at the hospital for disposal?a	Yes (versus no)	71.7% (377)	75.1% (251)	65.6% (126)	-9.5% [-17.7, -1.4]	0.026*

CI = confidence interval.

* P < 0.05 (chi-square test of independence: No unused opioids versus any unused opioids).

a Percentages calculated excluding missing responses.

b Confidence intervals adjusted using Bonferroni correction to control familywise error.

c Multiple selections were permitted; percentages may total more than 100%.

Many respondents reported unsafe opioid handling practices. Only 10% of respondents reported using a secure (locked) storage location; 90% reported an unlocked storage location. While 56% said they typically used a Health Canada-recommended disposal method [12] (i.e., return to the pharmacy or a take-back program), 44% reported neither of the recommended methods, with 14% reporting that they would not dispose of unused opioid medication. Eight percent reported sharing opioid medication (i.e., letting others use opioids prescribed to them and/or using opioids prescribed to someone else). Compared to respondents with no unused opioids, those with unused opioids at home were more likely to report unsafe handling practices, including storing opioids in an unsecured location (96% vs. 87% using unlocked storage, p = 0.001); disposing of opioids by throwing them in the garbage (23% vs. 12%, p = 0.001); stating that they would not dispose of opioids at all (21% vs 10%, p<0.001); and sharing prescription opioids (14% vs. 5%, p<0.001). Respondents in our sample who received storage and disposal instructions from a pharmacist or health care provider did report safer handling behaviors: they were less likely to have unused opioids at home (p = 0.005), more likely to keep opioids in a locked location (p<0.001), and more likely to dispose of opioids at a pharmacy or take-back program (p<0.001) (see S1A–S1C Table for comparative analysis of those who reported receiving instruction versus those who did not).

Seventy-two percent of respondents indicated they would be willing to return unused opioids in a potential hospital-based take-back program. Respondents with unused opioids were less willing to participate (66% vs. 75%, p = 0.026) (Table 2). Among the 28% of respondents who would not participate in the hypothetical program, the most common reasons given were preferring to dispose of the medication on their own (40%), concern about obtaining opioids again in a timely manner (29%), and fear that their pain would return (24%) (Table 3). Compared to respondents with no unused opioids, those with unused opioids at home were more likely to report fear that their pain would return (33% vs. 16%, p = 0.020); other factors were not significantly different between the two groups.

Table 3

Reasons for not wanting to participate in an opioid take-back program, overall and by presence of unused opioids at home.

		Unused opioid medication at home
Responsea	All respondents unwilling to participate, % (count) N = 149	No unused opioids, % (count) N = 83	Any unused opioids, % (count) N = 66	Difference [95% CI]	P
I am afraid my pain will come back and I’m not willing to be without it	23.5% (35)	15.7% (13)	33.3% (22)	17.7% [3.6, 31.1]	0.020*
If I need it again, I will not be able to get it from a doctor in a timely manner	28.9% (43)	26.5% (22)	31.8% (21)	5.3% [-9.3, 19.9]	0.597
I do not want to throw it away because I paid for it	10.1% (15)	6.0% (5)	15.2% (10)	9.1% [-1.2, 19.4]	0.118
My friends or family members may need it	3.4% (5)	3.6% (3)	3.0% (2)	-0.6% [-6.9, 6.3]	1.000
I would prefer to dispose of it myself	38.9% (58)	39.8% (33)	37.9% (25)	-1.9% [-17.3, 13.8]	0.948
Other reason	17.4% (26)	21.7% (18)	12.1% (8)	-9.6% [-21.1, 2.9]	0.190

CI = confidence interval.

* P < 0.05 (chi-square test of independence: No unused opioids versus any unused opioids).

a Multiple selections were permitted; percentages may total more than 100%.

The presence of minors or young adults in the household was not associated with using a secure opioid storage location (Table 4). Compared to respondents who used a locking opioid storage method, respondents who used non-locking storage methods reported similar rates of minors and young adults in the home. Of the 476 respondents who reported storing opioids in an unlocked location, 21% had at least one child (age 0 to 12) and 29% had at least one teenager or young adult (age 13 to 25) in the home.

Table 4

Presence of children, teenagers and/or young adults in the household versus opioid storage method, among current and former opioid users.

		Opioid storage type a
	Age group	Locked (N = 52)	Not locked (N = 476)	P
Do children, teenagers, or young adults live in your home or visit your home? b
	No children/teenagers/young adults reported	57.7% (30)	56.5% (269)	0.988
	Young children (age 0–6)	11.5% (6)	13.0% (62)	0.932
	Older children (age 7–12)	17.3% (9)	14.1% (67)	0.673
	Teenagers (age 13–17)	19.2% (10)	12.0% (57)	0.203
	Young adults (age 18–25)	19.2% (10)	21.8% (104)	0.796
Combined age groups:
	Derived: Any children (age 0–12)	23.1% (12)	20.6% (98)	0.811
	Derived: Any teenagers or young adults (age 13–25)	32.7% (17)	28.8% (137)	0.668

a 41 respondents who did not report their storage method were excluded.

b Multiple selections were permitted; percentages may total more than 100%.

* P < 0.05 (chi-square test of independence: Locked storage versus non-locked storage).

Discussion

This study reveals that many opioid-using orthopaedic patients have unsafe opioid handling practices, and report not receiving instruction on safely managing their prescription opioids from their pharmacist or HCP. In particular, patients with unused opioids in the home reported lower instruction rates, and almost half of this group had minors or young adults in the household. Most orthopaedic patients are willing to participate in a hospital-based opioid disposal program.

We found that orthopaedic patients frequently stored and disposed of opioids incorrectly, consistent with findings from U.S. studies [20]. Only 10% of respondents stored opioids securely, and only 41% of respondents disposed of unused opioids appropriately. A recent systematic review with 810 surgical patients concluded that 77% of patients insecurely stored their opioids and only 9% of patients followed the FDA-recommended disposal methods [21]. Improper storage and retention of unused opioids both increase the risk of opioid misuse, diversion, and accidental poisoning [22,23]. Suboptimal disposal may also contaminate environmental reservoirs [24,25]. Medication take-back programs and coordinated initiatives, such as National Prescription Drug Drop-Off Day in Canada, have been established to promote safe storage and disposal practices and to reduce the number of unused tablets readily available within the community [26]. While promising, these programs tend to have poor uptake and remain in their rudimentary stages of implementation [27,28]. Furthermore, to the best of our knowledge, these programs are seldom promoted in the hospital setting.

While the orthopaedic patients in our study did not explicitly report the reason for their opioid use, it is likely that many of their prescriptions were related to orthopaedic conditions. Short-term opioid use remains essential in the management of postoperative pain or acute orthopaedic injuries [29-34]. Therefore, in order to minimize opioid diversion opportunities, it is imperative that patients receive adequate education regarding safe storage and disposal of opioids. Only a third of patients in our sample recalled receiving instructions on safe opioid handling practices from their pharmacist, and only 10% from other healthcare providers. Other studies in both surgery and emergency departments have found similar low rates of instruction [35-38]. These results suggest a need for both hospital- and community-based HCPs to address not only prescribing practices [10,11,39], but also patients’ opioid handling knowledge (and ultimately, behaviour).

Consistent with other studies, one third of surveyed patients reported having opioids at home that were no longer being used [20,40-42]. We found that these patients were less willing to participate in a hospital-based take-back program compared to those with no unused opioids, citing fear that their pain would return, concerns about untimely access to more opioids, and that they did not want to dispose of medication they paid for. Furthermore, these patients were less likely to report receiving opioid handling education and using safe handling methods, and almost half of the group reported having minors or young adults in the household. This combination of factors may signify a high risk of opioid diversion in this group.

In our study, 8% of current or former opioid users reported sharing their medications with others, and of the 90% who stored their opioids in an unsecured location, 44% reported children, teenagers, or young adults in their household. Previous research indicates that drug misuse is directly linked to the presence of leftover medications in unsecured household cabinets and through sharing unused medications [22,37,43-45]. In fact, 70%-75% of abusers obtained opioids through methods of diversion and only 5% from drug dealers or strangers [46-51]. Consistent with our findings, recent studies have demonstrated that prior instruction in safe opioid handling practices was highly associated with returning medications to a pharmacy, and was the factor most strongly associated with returning medications to a clinician [52-57]. Consequently, it is essential that orthopaedic surgeons, as well as other hospital and community HCPs allocate sufficient time toward educating patients on safe opioid handling practices and the potential danger of opioid diversion. Our subsequent work will aim to determine whether a hospital-based education program is effective for promoting safer opioid handling among patients.

Limitations

This study had several limitations. Media attention and stigma surrounding opioids may have contributed to a social desirability bias, leading participants to underreport opioid use, retention of unused opioids, and unsafe handling practices. An anonymous survey and survey return mechanism were used to minimize this effect. Recall bias may also lead participants to misreport prior education on opioid handling. Second, the voluntary nature of the questionnaire creates a risk of selection bias. The representativeness of the sample cannot be confirmed, as the number of patients who declined to participate was not tracked. Although the sample’s age and gender distribution is similar to that of the general orthopaedic population [58], the study was conducted in a single large, urban, tertiary care centre which may limit the generalizability of the findings. Lastly, the study data was collected at a single time point; patients’ opioid handling practices may have changed with increased awareness of the opioid epidemic.

Conclusion

Patients attending an ambulatory Orthopedic clinic who have been prescribed opioids commonly report possession of unused opioids and unsafe opioid handling practices. As well, relatively few patients prescribed opioids report receiving education on safe opioid handling practices from their pharmacist, and even fewer from other healthcare providers. Our findings reveal a significant opportunity for hospital-driven opioid stewardship. While overprescribing of opioids remains a critical issue, our study suggests a concurrent need to address patient knowledge and behavior regarding opioid handling in order to reduce the risk of opioid diversion in the households of opioid-using patients.

Comparative analysis of opioid-using respondents by receipt of opioid storage and disposal instruction.

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Public safety survey.

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21 Jun 2021

PONE-D-21-17272

The potential for diversion of prescribed opioids among orthopaedic patients: results of an anonymous patient survey

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1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

3. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

5. Thank you for stating the following in the Competing Interests section:

'I have read the journal's policy and the authors of this manuscript have the following

competing interests: Y. Raja Rampersaud has received royalties from Medtronic and

holds investments in Arthur Health Corporation.

All other co-authors have no competing interests to report.'

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear authors,

I think this analysis in your article is an important finding, considering the opioid epidemic in Canada and the numbers you raised for hospitalization.

The abstract clearly summarizes the study and is adequate.

The introduction is adequate.

For the method part, you write that existing studies defined safe storage location as protected by a lock. So why did you consider both latch and lock as safe for your study? A Latch for me is not really safe, as beginning with small children or anyone else getting to that room will be able to open it. Does your data change when you only consider a lock as a safe storage location?

What would be interesting is establishing a education program e.g. in your clinic and to the measurement again, to see if your hypothesis that education in safe storage and so on has any effect on return rates or safe storage. In the same way it might be interesting to investigate, as you say, if patient handling with opioids has changed by the awareness of the opiod epidemic und media attention.

You state that patients with unused opioids at home have significantly less likely received storage information or disposal instructions. The questions that raises to me is on the other hand is if patients who have received storage information and disposal instructions are more likely to use a safe storage location, have higher rates in returning opioids, have less unused opioids at home and so on. This is the questions to answer if one wants to see if education on opiod use has any effect. This is somehow the conclusion of your study, that more education is needed, but is there any proof that education changes the rates of safe opiod handling? Can you answer that out of your data?

Reviewer #2: - Abstract/ Results: consider adding a denomination, e.g. '(past) prescription opioid use' to better describe the study population in summary.

- Table 2 is an extensive table, leading to reduced legibility. Please provide some separation between parts of the table, either within this table, or by creating multiple tables.

- Discussion, second paragraph: limitations were described in profound detail. However, it could be of interest to add some background information on chronic opioid use in relation to the study population. E.g.: J Pain. 2017 November ; 18(11): 1374–1383

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: FGAM van Haren

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

5 Aug 2021

Please see attached Response to Reviewers document.

Submitted filename: opioid survey_response to reviewers.docx

Click here for additional data file.

16 Aug 2021

The potential for diversion of prescribed opioids among orthopaedic patients: results of an anonymous patient survey

PONE-D-21-17272R1

Dear Dr. Rampersaud,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Kingston Rajiah

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All points that have been raised after the first submission have been answered and corrected in the new submission, good work.

Reviewer #2: Already of good quality, comment have been adequately addressed. Already of good quality, comment have been adequately addressed.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

18 Aug 2021

PONE-D-21-17272R1

The potential for diversion of prescribed opioids among orthopaedic patients: results of an anonymous patient survey

Dear Dr. Rampersaud:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Kingston Rajiah

Academic Editor

PLOS ONE