What is adolescent low back pain? Current definitions used to define the adolescent with low back pain

Abstract

Adolescent low back pain (ALBP) is a common form of adolescent morbidity which remains poorly understood. When attempting a meta-analysis of observational studies into ALBP, in an effort to better understand associated risk factors, it is important that the studies involved are homogenic, particularly in terms of the dependent and independent variables. Our preliminary reading highlighted the potential for lack of homogeneity in descriptors used for ALBP. This review identified 39 studies of ALBP prevalence which fulfilled the inclusion criteria, ie, English language, involving adolescents (aged 10 to 19 years), pain localized to lumbar region, and not involving specific subgroups such as athletes and dancers. Descriptions for ALBP used in the literature were categorized into three categories: general ALBP, chronic/recurrent ALBP, and severe/disabling ALBP. Whilst the comparison of period prevalence rates for each category suggest that the three represent different forms of ALBP, it remains unclear whether they represented different stages on a continuum, or represent separate entities. The optimal period prevalence for ALBP recollection depends on the category of ALBP. For general ALBP the optimal period prevalence appears to be up to 12 months, with average lifetime prevalence rates similar to 1-year prevalence rates, suggesting an influence of memory decay on pain recall.

Keywords:

• lumbar pain
• teenager
• adolescent

Introduction

Since the 1980s there has been an increasing appreciation of the extent of adolescent low back pain (ALBP) in the community.^1–3 This shift in awareness appears to have resulted from a series of international epidemiological studies which identified a significant prevalence of reported spinal pain in otherwise ‘healthy’ adolescents.^4–6

This increased awareness of the prevalence of ALBP is reflected in the increase in published research on ALBP over the past 30 years. For this paper, ALBP refers to low back pain present in adolescents, ie, between 10 and 19 years of age, of no known pathological cause. The published research related to ALBP can be characterized into two major streams. The first stream focuses on the prevalence of ALBP and the associated risk factors, whilst the second stream explores the clinical management of the adolescent presenting with low back pain. This paper focuses on the first of these streams, ie, observational studies which describe the prevalence of ALBP in specific population groups and the associated risk factors.

Despite an increasing number of observational studies into this common form of adolescent morbidity and associated factors, there remains little agreement on the risk factors.^7,8 When presented with a number of observational studies, focused on the one condition, meta-analysis has been promoted as the best approach for combining the datasets.⁹ However, valid meta-analysis depends on homogeneity of the included studies. When significant inter-study differences in methodologies exist, this hinders the ability to amalgamate datasets for analytical purposes.

Defining ALBP

Our preliminary reading highlighted the potential for a lack of homogeneity in the descriptors of ALBP. This paper reviews the definitions used in the literature related to ALBP prevalence. By describing the current situation in terms of the definitions of ALBP used, the foundation is set for further research in identifying a common classification system for use in ALBP. The terms used to present the details of research, in particular dependant variables such as ALBP, are important as they facilitate communication and common understanding.¹⁰ To further highlight the effect of definitional differences on ALBP prevalence, the studies identified in this review were categorized into three broad subgroups, according to their definitions, and the relative prevalence of ALBP between these groups was compared using period prevalence rates.

Significant progress has been made in international recognition and understanding of ALBP, but two issues remain. The first issue, common to adult research, is the difficulty in arriving at an agreed diagnosis for the LBP.¹¹ The complexity of the spine, both anatomically and functionally, makes effective diagnosis difficult. Current clinical, surgical, and radiographic investigatory techniques are hampered as the pain-sensitive structures are often not amenable to direct anatomical scrutiny.¹¹ Although there are well-reported descriptions of a range of clinical presentations, an understanding of pain itself, in terms of etiology and pain mechanisms, is less well developed.¹²

In the adult population, over 50% of LBP sufferers have an unclear diagnosis, despite extensive laboratory and radiographic investigations.¹³ In nine out of 10 cases, adult spinal pain has been described as transient, related to posture or strain, with recovery occurring in a short period of time.¹⁴ Amongst the adult population, 60% to 80% will suffer an episode of LBP in their lifetime with a subset of 2% to 7% reporting ongoing chronic, recurrent pain.¹⁵

The second issue, related to etiology, is the range of potentially interdependent and time-dependent factors that influence the reporting of ALBP. These factors, which may present as risk factors or prognostic factors, affect the development and progression of the condition. The wide variation in timing and tempo of the developmental processes within an adolescent population further compounds the difficulty in identifying and categorizing these factors. Epidemiological studies play an important role in providing information on the etiology, natural history, impact of health conditions such as ALBP, and the interrelationships between potential risk and prognostic factors.¹⁶

These two issues are intrinsically linked to progressing the understanding of ALBP. The ability to identify causes of ALBP is dependent on the ability to accurately define and classify ALBP. It is naïve to consider that all forms of self-reported ALBP are the same and, likewise, optimistic to consider that all types of ALBP are caused by the same factors.

Observational studies into the prevalence of ALBP have generally avoided identifying a pathoanatomical cause for the pain. The etiology for the ALBP reported in these studies remains unknown, with the range of potential causes outlined in Table 1.

Table 1 Potential causes for ALBP

Primary spinal disorders Mechanical Disc lesions or herniations Spondylolysis and spondylolisthesis Scheuermanns disease Overuse injuries Traumatic injuries Congenital disorders – scoliosis, spinal fusion, spinalstenosis Inflammatory/Infectious Diskitis Disc calcifications Inflammatory rheumatic disorders Infections of the bone/soft tissue Arachnoiditis Neoplasms Benign tumors – osteoid osteoma, osteochondroma, lipoma, giant cell tumor, Malignant tumors – Ewings sarcoma, osteogenic sarcoma, neuroblastoma, cord tumors Radiation Therapy sequalae Systemic or nonspinal diseases Hematolgic disorders – sickle cell, leukemia, Hodgkin’s, and non-Hodgkin’s lymphoma Aortic dissection Intra-abdominal diseases Fibrositis Marfans disease Psychological Nonspecific causes

Notes: Adapted from Balague and Nordin,¹⁷ and King.¹⁸

When attempting to understand the prevalence and the behavior of potential risk factors for a condition such as ALBP through observational studies, the first step is to classify the subjects who have the condition. In some conditions this classification process is self explanatory, often through the presence of a measurable biological marker, whilst in other conditions, such as ALBP, it is harder to define.

The measure most commonly collected is an adolescent’s self-report of pain. However, self-reported pain can be described in multidimensional terms, using measures such as chronicity, frequency, episode duration,¹⁹ intensity (ie, pain effects), severity (including effect on activities of daily living [ADL]),^16,20 and recall prevalence. These measures are not mutually exclusive, with each describing an aspect of the pain experience. However, of these measures, recall prevalence is the most stable across the studies as the comparative scale (ie, period of recall) is standardized.

Recall prevalence is described in terms of the period of recall required:

• – 1-week prevalence is the proportion of the population who experienced symptoms over the week preceding the questioning.

• – 1-month prevalence is the proportion of the population who experienced symptoms over the month preceding the questioning.

• – 1-year prevalence is the proportion of the population who experienced symptoms over the 12 months preceding the questioning.

• – Lifetime prevalence is the portion of the population who experienced symptoms at any stage of their life preceding the questioning.

Whilst point prevalence refers to pain at the time of the assessment, some authors have taken a broader view and include 1-week prevalence data within their definition of point prevalence.²¹

The ability of subjects to accurately report on their pain prevalence over any of these periods will depend on their ability to recall the pain.¹⁹ A number of factors may influence the optimal period over which to collect data in determining the prevalence of ALBP in a community.

Memory decay is a term used to describe the gradual memory loss that occurs over time when recalling significant events.²² Three factors determine the extent to which memory decay will affect the data collected on ALBP prevalence: (a) the longer the time period of recall the greater the potential influence of memory decay, (b) the more significant the incident the less likely that memory decay will occur, and (c) the innate ability of the individual to recall events will influence the rate of memory decay.

Forward telescoping describes the tendency for a subject to recollect events, such as LBP, as occurring more recently than they actually did.²² An example would be an adolescent who had an episode of LBP two years ago, but who includes it within 1-year prevalence data. This will tend to increase the reported prevalence of LBP when investigating period prevalence, particularly over shorter time periods.

The shortest period of recall is pain at the time of data collection, ie, point prevalence. However, too short a period of recall may limit the ability to collect data from sufficient subjects to develop an understanding of the risk factors associated with ALBP. This is counterbalanced by the notion that collection of data on ALBP reported at the time of questionnaire delivery will significantly reduce the potential for memory decay to affect the data validity.

The longest period of recall is lifetime prevalence, where the subject is asked if they have had any episode of LBP. The use of lifetime prevalence will negate the influence of forward telescoping, however memory decay presents a significant influence.

It remains unclear what is the most valid or reliable period prevalence to use for the collection of ALBP prevalence rates, however, due to the stable nature of recall prevalence definition across the literature, this measure will be used in this review to compare the potential effect of differing ALBP definitions on prevalence rates.

Material and methods

Literature search

The electronic databases of MEDLINE, EMBASE, and CINAHL were searched using the Medical Subject Headings: Adolescent, Low Back, Pain, and the keywords: adolescent, children, low back pain, spinal pain, lumbar pain. Bibliographies of relevant articles were manually searched. No age restrictions were applied to the search strategy.

Inclusion criteria

No attempt was made to exclude studies based on study quality. Articles were included if they were in English language and available in full text. Studies were excluded if they did not specifically describe the low back area, did not focus on adolescents (aged between 10 and 19 years), were focused on specific causes of ALBP (ie, related to backpack carriage), or related to specific adolescent subpopulations (ie, athletes).

Analysis

All articles were reviewed for the description of ALBP used. This definition was either stated directly in the paper or was extrapolated from the questions used to collect ALBP data. The definitions were then collated and characterized into three groups, based on their defining characteristics:

1. General ALBP: any ALBP, ie, there were no restrictions placed on the reported ALBP.

2. Chronic/recurrent ALBP: low back pain that was characterized by a measure of chronicity or recurrence.

3. Severe/disabling ALBP: low back pain that was characterized by a measure of severity, ie, effect on activity.

ALBP prevalencedata from each study by recall prevalence was recorded in an Excel^© (Microsoft Corporation, Redmond, WA) spreadsheet for further analysis.

Results

Article selection

The initial literature search yielded 89 citations. These articles were screened for relevance and content. Of those, 42 did not meet eligibility criteria, leaving 47 articles which underwent detailed review. The main reasons for failing to meet eligibility criteria was a failure to define the area of the low back, a focus on specific subgroups of adolescents (athletes, dancers), and failure to specifically present prevalence rates for subjects between the ages 10 to 19 years of age. Of the 47 articles selected three involved re-analysis of data presented in a previous study, and were therefore not included in the prevalence review. Table 2 and Figure 1 present the characteristics of the included studies.

Figure 1 Number of studies on adolescent low back pain prevalence published by decade.

Figure 2 Relationship between average period prevalence rates for general adolescent low back pain.

Table 2 Characteristics of the studies presenting ALBP prevalence data used in this review

		Studies		Subjects
		n	%	n	%
Origin of study sample	European	34	77	267,976	96.3
	Middle East	2	4.6	5,400	1.9
	Australasia	3	6.8	2,124	0.8
	Americas	3	6.8	1,879	0.7
	Africa	2	4.6	826	0.3
Data collection methodology	School	40	91	60,083	21.6
	National Survey	4	9	218,122	78.4
Period recall (% add up to greater than 100 as some studies use multiple recall periods)	PP	14	31.8	21,737	7.8
	1M	15	34.1	15,503	5.6
	3M	3	6.8	4,871	1.8
	6M	6	13.6	206,988	74.4
	1Y	12	27.3	36,935	13.3
	LT	20	45.5	38,247	13.7

Abbreviations: ALBP, adolescent low back pain; PP, point prevalence; 1W, 1-week; 1M, 1-month; 3M, 3-month; 6M, 6-month; 1Y, 1-year; LT, lifetime.

Due to the small number of subjects that presented ALBP prevalence data once broken down by gender and chronological age, the data for average prevalence for both male and female over the recall periods were used in this review.

Table 3 presents the definitions for ALBP used in the studies identified in this review, and the subsequent groupings of the ALBP type based on the definition used.

Table 3 Characteristics of the studies presenting ALBP prevalence data used in this review

Study	Definition	ALBP grouping
Grimmer and Williams,^Citation32 Cakmak et al,^Citation27 Legg et al,^Citation8 Mogensen et al,^Citation44 Wedderkop et al,^Citation60 Balague et al,^Citation25,Citation4,Citation21 Prista et al,^Citation49 Harreby et al,^Citation33 Shehab et al^Citation51	Any pain in the low back.	General
Watson et al,^Citation58 Murphy et al,^Citation45,Citation46 Jones et al^Citation35,Citation38	Low back pain lasting for one day or longer.	General
Auvinen et al^Citation23	Any pain or aching in the low back area.	General
Olsen et al^Citation47	Pain or other trouble with the lower part of the back.	General
Sjolie^Citation53	Pain, ache, or discomfort in the lower back, not related to trauma or menstrual pain.	General
Ebrall,^Citation19 Skoffer and Foldspang^Citation54	Any pain or discomfort in the low back.	General
Mierau et al^Citation43	Pain, soreness, or hurt over the low back.	General
Kristensen et al^Citation40	Any ache, pain, or discomfort in the lower back.	General
Jones et al^Citation37	Any low back pain or pain occurring regularly.	General, Chronic/recurrent
Vikat et al^Citation57	Pain in the low back at least weekly.	Chronic/recurrent
El-Metwally et al,^Citation29 Mikkelson et al^Citation61	Any pain or ache in the low back – paper reported on monthly or weekly recurrence only.	Chronic/recurrent
Feldman et al^Citation30,Citation31	Low back pain with a frequency of at least once per week.	Chronic/recurrent
Hakala et al^Citation34	Back pain at least weekly over the past half a year.	Chronic/recurrent
Diepenmaat et al^Citation28	Pain lasting a day or longer with >4 days per month.	Chronic/recurrent
Taimela et al,^Citation2 Kujala et al^Citation41	Low back pain that interfered with school, work, or leisure activities.	Severe/disabling
Masiero et al^Citation42	Any nonoccasional pain that in some way limited the student in daily activities.	Severe/disabling
Burton et al^Citation26	Quite bad pain, other than occasional twinges.	Severe/disabling
Prendeville and Dockrell^Citation48	An episode of low back pain and/or discomfort that interrupted normal daily activities and/or required treatment. Low back pain due to any structural abnormalities or menstrual pain is excluded.	Severe/disabling

Table 4 presents the prevalence rates reported in the studies, by period prevalence and ALBP category. These prevalence rates are summarized in Table 5.

Table 4 Period prevalence rates for each category of ALBP

Study		Prevalence (%)
		PP-1W	1M	3M	6M	1Y	LT
General low back pain	Auvinen et al^Citation23				39
	Balague et al^Citation4	13					40
	Balague et al^Citation21	9.4					32.5
	Balague et al^Citation24						20
	Balague et al^Citation25						51
	Bejia et al^Citation36	13					28.4
	Cakmak et al^Citation27						32
	Ebrall^Citation19	16.7					57
	Grimmer and Williams^Citation32	25.4
	Harreby et al^Citation33	13.9	30.6			50.8	58.9
	Jones et al^Citation35		18.6
	Jones et al^Citation37	15.5					40.2
	Jones et al^Citation38		25.4
	Kjaer et al^Citation39		22
	Kovacs et al^Citation50	25					61
	Kristensen et al^Citation40						63
	Legg et al^Citation8						48
	Mierau et al^Citation43				33
	Mogensen et al^Citation44		40
	Mohseni-Bandpei et al^Citation62	15	14		15.6	17.4
	Murphy et al^Citation45	20	36
	Murphy et al^Citation46		22				55
	Olsen et al^Citation47					22	30.4
	Prista et al^Citation49						58
	Shehab et al^Citation51	35					57.8
	Sjolie^Citation52,Citation53					57
	Skoffer and Foldspang^Citation54			51.3		60.3	64.8
	Staes et al^Citation55		38
	Troussier et al^Citation56	23
	Van Gent et al^Citation63		46.5
Recurrent	Watson et al^Citation58,Citation59		23.9
	Wedderkopp et al^Citation60		14.8
	Diepenmaat et al^Citation28		7.5
	El-Metwally et al^Citation29			22.4
	Feldman et al^Citation30,Citation31				24.9
	Balague et al^Citation25						48
	Jones et al^Citation37					13.1
	Prista et al^Citation49		12			13.5	28
	Shehab et al^Citation51						36
	Staes et al^Citation55		3
	Sjolie^Citation53					32
	Vikat et al^Citation57				27
	Hakala et al^Citation34				11.7
Disabling	Kristensen et al^Citation40					22
	Skoffer and Foldspang^Citation54			24.2
	Kujala et al^Citation41					10.7
	Masiero et al^Citation42					20.5
	Prendeville and Dockrell^Citation48	17				28	41.5
	Taimela et al^Citation2					14.2
	Kjaer et al^Citation39		8
	Balague et al^Citation25		24.3
	Burton et al^Citation26	7					30

Abbreviations: ALBP, adolescent low back pain; PP, point prevalence; 1W, 1-week; 1M, 1-month; 3M, 3-month; 6M, 6-month; 1Y, 1-year; LT, lifetime

Table 5 Summary of period prevalence rates for each category of adolescent low back pain

		Prevalence rates (%)
		General	Severe/disabling	Recurrent/chronic
0–1 week	Average (50th %ile)	16.1	12	N/A
	Range (%min–%max)	9.4–35	7–17	N/A
	No of Studies	12	2	N/A
1-month	Average (50th %ile)	24.65	16.15	7.5
	Range (%min–%max)	14–46.5	8–24.3	3–12
	No of Studies	12	2	3
3-month	Average (50th %ile)	51.3	24.2	22.4
	Range (%min–%max)	51.3	24.2	22.4
	No of Studies	1	1	1
6-month	Average (50th %ile)	33	N/A	24.9
	Range (%min–%max)	15.6–39	N/A	11.7–27
	No of Studies	3	N/A	3
12-month	Average (50th %ile)	50.8	20.5	13.5
	Range (%min–%max)	17.4–60.3	10.7–28	13.1–32
	No of Studies	5	5	3
Lifetime	Average (50th %ile)	51	35.75	36
	Range (%min–%max)	20–64.8	30–41.5	28–48
	No of Studies	17	2	3

General ALBP was the most common definition of ALBP from the literature reviewed, and therefore presented the most data for each period prevalence. The 1-week, 1-month, and 1-year prevalence rates for this category of ALBP were graphed against a 12-month timeline, and a logarithmic trend line applied to these points. As the relationship between period prevalence rates was not expected to be linear, ie, a ‘ceiling effect’ was expected over an extended period, a logarithmic trend line was used to describe the relationship between period prevalence rates over the 12-month period.

The logarithmic trend line for general ALBP over the 12-month period and the corresponding correlation coefficient is presented below (where y = prevalence rate (%), and x = weeks). $\text{General}\hspace{0.17em}\text{ALBP}:\text{y}=7.2149\text{ln}(\text{x})+17.978\hspace{0.17em}{\text{R}}^2=0.87$

Discussion

This review identified that within the literature related to the prevalence of low back pain amongst adolescents, there were a range of definitions used. When these definitions were classified into three broad categories they represented different prevalence rates.

The particular concern identified by this study was that most papers reported their adolescent subjects as suffering low back pain, without consideration of the definitional parameters. This constrains the ability to synthesize the literature to identify risk factors, as studies with different pain definitions (in terms of severity, chronicity, and intensity) lack homogeneity, as they are describing different pain situations.¹⁶ Within each of the three broad classifications used in this review, there were significant differences in the period prevalence rates across studies, suggesting a wide variation in ALBP prevalence rates.

The logarithmic trend line calculated in this paper represents the behavior of the average ALBP prevalence rate for each period recall from the literature available. As more studies are published, which present prevalence data for each category of ALBP, the robustness of this formula should improve. This trend line can be seen to represent the ‘natural’ history of ALBP within a normal adolescent population. As the robustness of this formula improves, it presents a unique measure to review the success of any intervention aiming to reduce the prevalence of ALBP.

Whilst all of these studies reported on the prevalence of ALBP, the differing definitions used mean that they may be referring to different forms of ALBP. When attempting to identify risk factors it seems prudent to ensure that the form of ALBP is the same across the population studied. When collating and analyzing evidence from the literature, it is important to compare “apples with apples, and oranges with oranges.” In the situation described in this paper, it is not certain that this is currently the case with ALBP.

It remains unclear whether the different definitions refer to different forms of ALBP, or to different points along a continuum of one form of ALBP. Whilst general ALBP reflects any low back pain, chronic/recurrent ALBP and severe/disabling ALBP represents pain of a specific form.

Five examples of question wording are provided below:

1. Any ache, pain, or discomfort in the lower back

2. Any pain in the low back

3. Low back pain lasting for one day or longer

4. Pain in the low back at least weekly

5. Low back pain that that interfered with school, work, or leisure activities.

These five different definitions would seem to refer to different types of ALBP.

Whilst some studies have attempted to define ALBP in terms of chronicity, severity, frequency, or episode duration, they have often failed to provide a well defined set of parameters for each measure. For example, chronicity is widely used in both the adult and adolescent LBP research literature, however it remains a poorly defined term that lacks consensus.²⁰ Chronicity can be viewed on a continuum, from an always present condition at one end through to a condition that recurs regularly at the other. Diepenmaat et al²⁸ defined ALBP as greater than four days per month of pain, and ignored any report of ALBP less than three days ALBP per month. In the Mikkelson et al⁶¹ definition, for a person to be considered to have ALBP they must have had it for at least once a week over the previous three months. Failure to report weekly pain over a three month period classified the subject as having no pain.

Feldman et al³¹ used a definition of ALBP as low back pain reported by adolescents which occurred at least once a week for six months. Anything less than this was deemed to be ‘transient, inconsequential’ pain. Alternatively, Hakala et al³⁴ included those subjects reporting monthly low back pain in the previous six months in the group without ALBP. Statements such as, “It is probable that a single attack of mild LBP once a year has no particular significance for one’s health status,”³³ remain unsubstantiated.

None of the studies, which classified ALBP according to chronicity, severity, or frequency, provided any justification for these classifications. Whilst all of the studies reviewed described their adolescent subjects as having low back pain, it would facilitate discussions if the description included consideration of the category of ALBP. Table 5 indicates that over the period prevalence rates the reported rate of chronic/recurrent or severe/disabling ALBP (ie, where a definition involved a criterion of recurrences or effects on activities of daily living) were lower than that for the general ALBP.

The period over which the subjects have been asked to recall any episodes of ALBP also varied significantly between studies.

In this review, there was little difference between the average lifetime prevalence (53%) and the 1-year prevalence (53.9%) of general ALBP. The longer the duration of recall the greater the potential for forgetfulness with extensive periods potentially providing unreliable data.¹⁶ It is more likely in lifetime prevalence data that the results are more reflective of significant episodes, rather than less limiting or less severe episodes.

Burton et al²⁶ found a high level of forgetfulness of previous LBP (1-year prevalence) in a group of 216 schoolchildren studied over the five years of their secondary schooling. Almost 60% of the students who reported LBP forgot at least one previous episode of spinal pain during annual questioning. This study suggested that with the use of a 1-year recall period, the influence of memory decay may significantly affect the accuracy of the prevalence data.

The effect of memory decay on the lifetime prevalence rate appears less significant for chronic/recurrent or severe/disabling ALBP. This difference between general ALBP and the other two categories may reflect the influence of a ‘saliency rule’, where more significant episodes are remembered more than less significant events.

Conclusion

This review of the ALBP prevalence literature identified a range of definitions used to define low back pain in adolescents.

The review of the ALBP prevalence data identified that the prevalence rates differed between three categories of ALBP definitions, ie, general ALBP, chronic/recurrent ALBP, and severe/disabling ALBP. It remains unclear how the three categories are related. Each category of ALBP may have different risk factors, which require further investigation.

For all types of ALBP, there appears to be a steady increase in average prevalence rates with the passing of time. For general ALBP this represented a relationship over 12 months represented by the equation y = 7.274 ln(x) + 17.68 R² = 0.792 (where y = prevalence rate (%), and x = weeks).

There did not appear to be significant difference between lifetime prevalence and 12-month prevalence in general ALBP, however for severe/disabling and chronic/recurrent ALBP a greater variation between the two prevalence rates was identified, potentially reflecting the effect of a saliency rule.

Differences in prevalence rates between the three categories of ALBP used in this review suggests that definitions of ALBP need to be standardized across studies, particularly in the search for risk factors. This will promote better homogeneity of studies into ALBP, allowing a stronger meta-analysis of the observational studies, and a better understanding of this condition.

Consideration of a classification system for ALBP will facilitate communication between the epidemiological and the clinical streams of ALBP research.

The most consistent reporting of ALBP appears to be for general ALBP, reported in period prevalence rates of 12 months or less.

Disclosures

The authors report no conflicts of interest in this work.