Table 5: PICO questions, recommendations, definitions of interventions, supporting evidence and comments regarding recent onset lumbar radiculopathy

PICO 11. Should patients with recent onset lumbar radiculopathy be advised of physical activity compared to rest? Recommendation 11 and level of evidence

↑ Consider recommending normal physical activity rather than reduced activity in the form of bed rest to patients with recent onset lumbar nerve root compression
Definition: Physical activity was defined as any physical activity as tolerated by the patient, e.g., walking, working, participating in leisure time activities, or exercises, with the purpose of staying active

Included studies: We identified two RCTs [64, 65]. Advice to stay active was compared to one [64] or 2 [65] weeks of bed rest

Primary outcomes: We did not observe any differences in effects on short term leg pain intensity [64, 65], back pain intensity [65], or activity limitations [64, 65]

Comment: The level of evidence was downgraded due to lack of a clinically relevant effect, imprecise effect estimate; and only one study (back pain intensity) A recommendation in favour of the intervention was formulated based on the potential positive effects of physical activity and the potential negative effects of rest on the patients’ general health

PICO 12. Should patients with recent onset lumbar radiculopathy be offered supervised exercise therapy in addition to usual care?

↑ Consider offering supervised exercise therapy to patients with recent onset lumbar nerve root compression as an add-on to usual treatment
Definition: Supervised exercise therapy was defined as exercises or physical activities, which had a therapeutic focus, were tailored and adjusted to the individual patient, and delivered by a trained healthcare professional. These included directional exercises, motor control exercise, nerve mobilisation, or strength exercises

Included studies: In total, six RCTs were identified [29, 66–70]. The intervention consisted of motor control exercises [66, 70], directional exercises combined with advice [67] or neuromuscular control exercises [69], isometric exercises [68], or general exercises [29]. This was compared to advice [66, 67], advice and general exercises [70], sham exercises [69], rest [68], and usual GP care [29]

Primary outcomes: A clinically relevant effect in favour of the intervention was observed on short term leg pain intensity [29, 66–70], and a small, statistically significant effect on short term back pain intensity [29, 67, 70]. We did not observe differences in effects on short term activity limitations [29, 67, 69, 70] or neurological deficits [69, 70]

Comments: The level of evidence was downgraded due to lack of transferability (inconsistent comparisons) and imprecise effect estimate

PICO 13. Should patients with recent onset lumbar radiculopathy be offered directional exercise compared to motor control exercise?

↑ Consider offering directional exercise or motor control exercise to patients with recent onset lumbar nerve root compression. There is no documentation of a clinically relevant difference between the two types of treatment
Definitions: Directional exercise was defined as repeated movement in a specific direction that alleviate referred pain based on the concept of mechanical diagnosis and therapy (MTD) [71] Motor control exercise was defined as core stability training exercises focussing on the deep core musculature supporting the spine, and performed without pain provocation and typically with the spine in a neutral position

Included studies: Based on the literature search of PICO 12, four RCTs were included [66, 67, 69, 70]. None of the included studies did a head-to-head comparison, and consequently an indirect comparison was made

Primary outcomes: We did not observe a statistically significant difference between the two interventions on short term leg pain intensity [66, 67, 69, 70] back pain intensity [67, 70], activity limitations [67, 69, 70], or neurological deficits [69]

Comments: The level of evidence was downgraded due to indirect comparisons, lack of transferability (variation in populations, interventions, and comparisons)

PICO 14. Should patients with recent onset lumbar radiculopathy be offered directional exercise in combination with neuromuscular control training compared to directional exercise alone?

√ It is good practice to consider combining directional exercises with motor control exercises rather than directional exercises alone for patients with recent onset lumbar nerve root compression, since a synergistic effect of the two interventions cannot be ruled out
Definition: Combined exercise therapy was defined as treatment consisting of a combination of various exercises tailored to the individual patient and adjusted per his or her symptoms, and delivered by a healthcare professional. The focus of this question was specifically on directional exercises and motor control as defined in PICO 13

Included studies: None identified

Comments: In the recommendation, consideration was given to the potential positive effect of both direction-specific exercises and neuromuscular control training. The working group agree that it is likely that, in combination, the two interventions may have a greater effect than individually and they are probably often given together

PICO 15. Should patients with recent onset lumbar radiculopathy be offered spinal manual therapy in addition to usual care?

↑ Consider offering spinal manual therapy to patients with recent onset lumbar nerve root compression as an add-on to the usual treatment
Definition: Manual therapy is defined in PICO 5

Included studies: We did not identify any studies that matched the patient population. Instead, three RCTs [67, 72, 73] identified from the literature search were included as indirect evidence; the first included patients with disc protrusion but intact annulus verified by MRI [72], the second study included patients with radiating leg pain of mixed duration (mean 24 months) with or without neurological symptoms [73], and one RCT included patients with and without radiating leg pain of mixed duration [67]. The interventions consisted of manipulation [72, 73] or manipulation, mobilisation and muscle stretching techniques [67]. Usual care was defined as advice alone [67], advice and sham manipulation [72], and home exercise [73]

Primary outcomes: We observed a small, statistically significant effect in favour of the intervention on short term leg pain intensity [67, 72, 73], back pain intensity [67, 72, 73] and activity limitations [67, 73]. No difference was observed on neurological deficits [67, 73]

Comments: The level of evidence was downgraded due to lack of transferability (downgraded twice due to mixed populations) and imprecise effect estimate

PICO 16. Should patients with recent onset lumbar radiculopathy be offered one of supervised exercise therapy or spinal manual therapy over the other?

↑ Consider recommending supervised exercise therapy or manual therapy to patients with recent onset lumbar nerve root compression. There is no documentation of a clinically relevant difference between the two interventions
Definition: Supervised exercise therapy is defined in PICO 12 and spinal manual therapy in PICO 5

Included studies: We did not identify any studies that did a head-to-head comparison of the interventions in the target population. Instead, indirect evidence was considered. We identified two RCTs that made a head-to-head comparison of directional exercises and manual therapy in patients with LBP[3 months with and without radiating leg pain and/or neurological symptoms [67, 74]. We further included indirect evidence from PICO 12 [29, 66–70] and PICO 15 [67, 72, 73] and based the recommendation on a comparison via usual care.

Primary outcomes: In patients with LBP[3 months, we did not observe differences in effects on short term leg pain intensity [67], back pain intensity [67, 74] or activity limitations [67, 74]. Same results were found in the indirect comparisons (short term leg pain intensity [29, 66–70, 72, 73], back pain intensity [29, 67, 70], activity limitations [29, 67, 69, 73], neurological deficits [69, 70])

Comments: The level of evidence was downgraded due to indirect comparisons, lack of transferability (population, symptom duration, and presence of leg pain), imprecise effect estimates and lack of reporting of the primary outcome neurological deficits

PICO 17. Should patients with recent onset lumbar radiculopathy be offered acupuncture in addition to usual care compared to usual care?

Recommendation 17 and level of evidence

√ It is not good practice to offer acupuncture on a routine basis to patients with recent onset lumbar nerve root compression
Definitions: Acupuncture is defined in PICO 7

Included studies: None identified.

Comments: The recommendation was formulated based on clinical experience and indirect evidence from two systematic reviews dealing with acupuncture for non-specific LBP [75] and complementary and alternative treatment [76]

PICO 18. Should patients with recent onset lumbar radiculopathy be offered MRI in addition to usual treatment compared to usual care?

↓ MRI should only be offered to patients with recent onset lumbar nerve root compression upon due consideration, since the beneficial effect is uncertain
Definition: Lumbar MRI within 1–12 weeks after start of symptoms, and relevant information to the patient regarding imagining findings

Included studies: We identified one RCT [46], in which patients were offered a clinical examination, MRI and usual care, and following randomised to either receive information regarding MRI findings or not. Usual care consisted of advice, medication, exercises and physiotherapy. Further, one cohort study [77] was included as indirect evidence

Primary outcomes: We did not observe any differences in effect on short term activity limitations, and short- and long term fear-avoidance [46] Comments: The level of evidence was downgraded due to lack of transferability (mixed population), only one study, and lack of reporting of primary outcomes (short term leg pain intensity, short term back pain intensity, and lumbar surgery)

The working group emphasised that information regarding imaging findings does not appear to improve clinical outcomes. Further, the potential harm (i.e., negative iatrogenic effects, increased surgical rates and overtreatment) outweigh the potential positive effects [77], which led to a recommendation against the intervention

PICO 19. Should patients with recent onset lumbar radiculopathy be offered extraforaminal glucocorticoid injection in the lumbar nerve root area in addition to usual treatment compared to usual care?

↓ Extraforaminal glucocorticoid injection in the lumbar nerve root area should only be offered to patients with recent onset lumbar nerve root compression upon due consideration, since the beneficial effect is probably short-lived and very low
Definition: X-ray guided glucocorticoid injection (with or without local anaesthetics) in the musculature adjacent to the nerve root of the affected nerve root (i.e., without penetration of the dura) in patients with a pre-existing MRI that excluded other pathologies and visualized the intervertebral space

Included studies: We did not identify any studies that evaluated this question. As indirect evidence, we identified a systematic review [78] and a health technology evaluation [79], including one RCT [80] that compared extraforaminal to epidural injections, and 24 studies comparing steroidal injection compared to placebo [81–104]

Primary outcomes: The overall result on short term pain intensity was a statistically significant, but clinically small, effect in favour of the intervention [78, 79]. No clinically relevant effect was seen on short term activity limitations [78, 79].

Comments: The level of evidence was downgraded due to indirect evidence, lack of transferability (procedures not routinely used in Denmark), imprecise effect estimate, and risk of bias. The evidence profile presented for this question in the Danish report and the above recommendations are based on Chou et al. [79] pp. 155, 156, 163, 165 and 170

In the recommendation, consideration was given to the time and effort that is required to perform the procedure, and the lack of clinically relevant short and long term effects, which led to a recommendation against the intervention

PICO 20. Should patients with recent onset lumbar radiculopathy and no effect of conservative treatment be offered a surgical consultation before 12 weeks compared to after 12 weeks?

√ It is good practice that patients with recent onset lumbar nerve root compression are assessed by a back surgeon within 12 weeks in cases where severe and disabling pain persists despite non-surgical treatment
Definition: A consultation with a surgical specialist within 12 weeks from the start of symptoms and with the aim to evaluate the potential need for lumbar surgery. This should be offered to patients who have undergone non-surgical treatment without improvement

Included studies: None identified

Comments: As indirect evidence, a systematic review on the timing of surgery [105], which included two studies on surgical versus non-surgical treatment [106, 107] informed a good practice recommendation

√ = Consensus recommendation
↓ = Weak recommendation against
↑ = Weak recommendation for.
See Tables 1 and 2 for definitions of level of evidence

Table 5: PICO questions, recommendations, definitions of interventions, supporting evidence and comments regarding recent onset lumbar radiculopathy

PICO 11. Should patients with recent onset lumbar radiculopathy be advised of physical activity compared to rest? Recommendation 11 and level of evidence ↑ Consider recommending normal physical activity rather than reduced activity in the form of bed rest to patients with recent onset lumbar nerve root compression		Definition: Physical activity was defined as any physical activity as tolerated by the patient, e.g., walking, working, participating in leisure time activities, or exercises, with the purpose of staying active Included studies: We identified two RCTs [64, 65]. Advice to stay active was compared to one [64] or 2 [65] weeks of bed rest Primary outcomes: We did not observe any differences in effects on short term leg pain intensity [64, 65], back pain intensity [65], or activity limitations [64, 65] Comment: The level of evidence was downgraded due to lack of a clinically relevant effect, imprecise effect estimate; and only one study (back pain intensity) A recommendation in favour of the intervention was formulated based on the potential positive effects of physical activity and the potential negative effects of rest on the patients’ general health

PICO 12. Should patients with recent onset lumbar radiculopathy be offered supervised exercise therapy in addition to usual care? ↑ Consider offering supervised exercise therapy to patients with recent onset lumbar nerve root compression as an add-on to usual treatment		Definition: Supervised exercise therapy was defined as exercises or physical activities, which had a therapeutic focus, were tailored and adjusted to the individual patient, and delivered by a trained healthcare professional. These included directional exercises, motor control exercise, nerve mobilisation, or strength exercises Included studies: In total, six RCTs were identified [29, 66–70]. The intervention consisted of motor control exercises [66, 70], directional exercises combined with advice [67] or neuromuscular control exercises [69], isometric exercises [68], or general exercises [29]. This was compared to advice [66, 67], advice and general exercises [70], sham exercises [69], rest [68], and usual GP care [29] Primary outcomes: A clinically relevant effect in favour of the intervention was observed on short term leg pain intensity [29, 66–70], and a small, statistically significant effect on short term back pain intensity [29, 67, 70]. We did not observe differences in effects on short term activity limitations [29, 67, 69, 70] or neurological deficits [69, 70] Comments: The level of evidence was downgraded due to lack of transferability (inconsistent comparisons) and imprecise effect estimate

PICO 13. Should patients with recent onset lumbar radiculopathy be offered directional exercise compared to motor control exercise? ↑ Consider offering directional exercise or motor control exercise to patients with recent onset lumbar nerve root compression. There is no documentation of a clinically relevant difference between the two types of treatment		Definitions: Directional exercise was defined as repeated movement in a specific direction that alleviate referred pain based on the concept of mechanical diagnosis and therapy (MTD) [71] Motor control exercise was defined as core stability training exercises focussing on the deep core musculature supporting the spine, and performed without pain provocation and typically with the spine in a neutral position Included studies: Based on the literature search of PICO 12, four RCTs were included [66, 67, 69, 70]. None of the included studies did a head-to-head comparison, and consequently an indirect comparison was made Primary outcomes: We did not observe a statistically significant difference between the two interventions on short term leg pain intensity [66, 67, 69, 70] back pain intensity [67, 70], activity limitations [67, 69, 70], or neurological deficits [69] Comments: The level of evidence was downgraded due to indirect comparisons, lack of transferability (variation in populations, interventions, and comparisons)

PICO 14. Should patients with recent onset lumbar radiculopathy be offered directional exercise in combination with neuromuscular control training compared to directional exercise alone? √ It is good practice to consider combining directional exercises with motor control exercises rather than directional exercises alone for patients with recent onset lumbar nerve root compression, since a synergistic effect of the two interventions cannot be ruled out		Definition: Combined exercise therapy was defined as treatment consisting of a combination of various exercises tailored to the individual patient and adjusted per his or her symptoms, and delivered by a healthcare professional. The focus of this question was specifically on directional exercises and motor control as defined in PICO 13 Included studies: None identified Comments: In the recommendation, consideration was given to the potential positive effect of both direction-specific exercises and neuromuscular control training. The working group agree that it is likely that, in combination, the two interventions may have a greater effect than individually and they are probably often given together

PICO 15. Should patients with recent onset lumbar radiculopathy be offered spinal manual therapy in addition to usual care? ↑ Consider offering spinal manual therapy to patients with recent onset lumbar nerve root compression as an add-on to the usual treatment		Definition: Manual therapy is defined in PICO 5 Included studies: We did not identify any studies that matched the patient population. Instead, three RCTs [67, 72, 73] identified from the literature search were included as indirect evidence; the first included patients with disc protrusion but intact annulus verified by MRI [72], the second study included patients with radiating leg pain of mixed duration (mean 24 months) with or without neurological symptoms [73], and one RCT included patients with and without radiating leg pain of mixed duration [67]. The interventions consisted of manipulation [72, 73] or manipulation, mobilisation and muscle stretching techniques [67]. Usual care was defined as advice alone [67], advice and sham manipulation [72], and home exercise [73] Primary outcomes: We observed a small, statistically significant effect in favour of the intervention on short term leg pain intensity [67, 72, 73], back pain intensity [67, 72, 73] and activity limitations [67, 73]. No difference was observed on neurological deficits [67, 73] Comments: The level of evidence was downgraded due to lack of transferability (downgraded twice due to mixed populations) and imprecise effect estimate

PICO 16. Should patients with recent onset lumbar radiculopathy be offered one of supervised exercise therapy or spinal manual therapy over the other? ↑ Consider recommending supervised exercise therapy or manual therapy to patients with recent onset lumbar nerve root compression. There is no documentation of a clinically relevant difference between the two interventions		Definition: Supervised exercise therapy is defined in PICO 12 and spinal manual therapy in PICO 5 Included studies: We did not identify any studies that did a head-to-head comparison of the interventions in the target population. Instead, indirect evidence was considered. We identified two RCTs that made a head-to-head comparison of directional exercises and manual therapy in patients with LBP[3 months with and without radiating leg pain and/or neurological symptoms [67, 74]. We further included indirect evidence from PICO 12 [29, 66–70] and PICO 15 [67, 72, 73] and based the recommendation on a comparison via usual care. Primary outcomes: In patients with LBP[3 months, we did not observe differences in effects on short term leg pain intensity [67], back pain intensity [67, 74] or activity limitations [67, 74]. Same results were found in the indirect comparisons (short term leg pain intensity [29, 66–70, 72, 73], back pain intensity [29, 67, 70], activity limitations [29, 67, 69, 73], neurological deficits [69, 70]) Comments: The level of evidence was downgraded due to indirect comparisons, lack of transferability (population, symptom duration, and presence of leg pain), imprecise effect estimates and lack of reporting of the primary outcome neurological deficits


PICO 17. Should patients with recent onset lumbar radiculopathy be offered acupuncture in addition to usual care compared to usual care? Recommendation 17 and level of evidence √ It is not good practice to offer acupuncture on a routine basis to patients with recent onset lumbar nerve root compression		Definitions: Acupuncture is defined in PICO 7 Included studies: None identified. Comments: The recommendation was formulated based on clinical experience and indirect evidence from two systematic reviews dealing with acupuncture for non-specific LBP [75] and complementary and alternative treatment [76]

PICO 18. Should patients with recent onset lumbar radiculopathy be offered MRI in addition to usual treatment compared to usual care? ↓ MRI should only be offered to patients with recent onset lumbar nerve root compression upon due consideration, since the beneficial effect is uncertain		Definition: Lumbar MRI within 1–12 weeks after start of symptoms, and relevant information to the patient regarding imagining findings Included studies: We identified one RCT [46], in which patients were offered a clinical examination, MRI and usual care, and following randomised to either receive information regarding MRI findings or not. Usual care consisted of advice, medication, exercises and physiotherapy. Further, one cohort study [77] was included as indirect evidence Primary outcomes: We did not observe any differences in effect on short term activity limitations, and short- and long term fear-avoidance [46] Comments: The level of evidence was downgraded due to lack of transferability (mixed population), only one study, and lack of reporting of primary outcomes (short term leg pain intensity, short term back pain intensity, and lumbar surgery) The working group emphasised that information regarding imaging findings does not appear to improve clinical outcomes. Further, the potential harm (i.e., negative iatrogenic effects, increased surgical rates and overtreatment) outweigh the potential positive effects [77], which led to a recommendation against the intervention

PICO 19. Should patients with recent onset lumbar radiculopathy be offered extraforaminal glucocorticoid injection in the lumbar nerve root area in addition to usual treatment compared to usual care? ↓ Extraforaminal glucocorticoid injection in the lumbar nerve root area should only be offered to patients with recent onset lumbar nerve root compression upon due consideration, since the beneficial effect is probably short-lived and very low		Definition: X-ray guided glucocorticoid injection (with or without local anaesthetics) in the musculature adjacent to the nerve root of the affected nerve root (i.e., without penetration of the dura) in patients with a pre-existing MRI that excluded other pathologies and visualized the intervertebral space Included studies: We did not identify any studies that evaluated this question. As indirect evidence, we identified a systematic review [78] and a health technology evaluation [79], including one RCT [80] that compared extraforaminal to epidural injections, and 24 studies comparing steroidal injection compared to placebo [81–104] Primary outcomes: The overall result on short term pain intensity was a statistically significant, but clinically small, effect in favour of the intervention [78, 79]. No clinically relevant effect was seen on short term activity limitations [78, 79]. Comments: The level of evidence was downgraded due to indirect evidence, lack of transferability (procedures not routinely used in Denmark), imprecise effect estimate, and risk of bias. The evidence profile presented for this question in the Danish report and the above recommendations are based on Chou et al. [79] pp. 155, 156, 163, 165 and 170 In the recommendation, consideration was given to the time and effort that is required to perform the procedure, and the lack of clinically relevant short and long term effects, which led to a recommendation against the intervention

PICO 20. Should patients with recent onset lumbar radiculopathy and no effect of conservative treatment be offered a surgical consultation before 12 weeks compared to after 12 weeks? √ It is good practice that patients with recent onset lumbar nerve root compression are assessed by a back surgeon within 12 weeks in cases where severe and disabling pain persists despite non-surgical treatment		Definition: A consultation with a surgical specialist within 12 weeks from the start of symptoms and with the aim to evaluate the potential need for lumbar surgery. This should be offered to patients who have undergone non-surgical treatment without improvement Included studies: None identified Comments: As indirect evidence, a systematic review on the timing of surgery [105], which included two studies on surgical versus non-surgical treatment [106, 107] informed a good practice recommendation

√ = Consensus recommendation ↓ = Weak recommendation against ↑ = Weak recommendation for. See Tables 1 and 2 for definitions of level of evidence