The Long‐Term Outcome of Transcutaneous Electrical Nerve Stimulation in the Treatment for Patients with Chronic Pain: A Randomized,Placebo‐Controlled Trial

Background: Transcutaneous electrical nerve stimulation (TENS) is an easy to use analgesic intervention. However, long‐term randomized placebo‐controlled studies with treatment periods of more than 3 months have not been executed to date. The aim of our study is to explore the long‐term (1 year) time course of the treatment effects of TENS compared to placebo (sham TENS). Method: We performed a randomized placebo‐controlled trial in patients with chronic pain (165), referred to a multidisciplinary pain center of a university hospital. Main outcome measures are the proportion of patients satisfied with treatment result and willing to continue treatment, pain intensity, pain disability, and perceived health status. Results: Survival analysis of time courses of proportions of satisfied patients revealed no significant differences (P = 0.79; log‐rank test) for TENS treatment compared to sham TENS. After 1 year, 30% (24/81) of the patients of the TENS group and 23% (19/82) of the sham TENS group were satisfied with treatment result. These patients experienced a mean overall improvement of 62.7% (n = 43). This effect was not significantly different between both groups. For satisfied patients, there were no differences in pain intensity or disability and perceived health status between the TENS and sham TENS group. Conclusions: Transcutaneous electrical nerve stimulation and sham TENS show similar effects in patients with chronic pain over a period of 1 year. We found support for a long sustained placebo effect.     

Feasibility Study of Transcutaneous Electrical Nerve Stimulation (TENS) for Cancer Bone Pain

This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.PerspectiveCancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.     

Intramuscular treatment of migraine attacks using diclofenac sodium: a crossover clinical trial

This was a double-blind clinical trial, with a crossover design, to compare the efficacy of a non-steroidal anti-inflammatory drug, diclofenac sodium, intramuscularly administered, and placebo in the treatment of migraine attacks. The drug was administered to 40 patients once a day in three consecutive migraine attacks. If pain still remained after 6 h following administration the patient was given a 100 mg diclofenac sodium suppository, in open condition. Evaluation was by a complete medical examination performed by the physician and by the patient completing a specially designed self-assessment card. A total of eight patients dropped out of the trial (all during placebo administration): three due to poor compliance, four for refusal to continue and one because no further migraine attacks developed. Results were analysed after having checked the absence of both period and carry-over effects. In all cases diclofenac sodium was more effective than placebo (P less than 0.01). This was also confirmed by data obtained from the patient self-assessment cards (P less than 0.001) and by preferences expressed by patients at the end of the trial (P less than 0.001). Tolerance to the drug was similar to that of placebo.     

Low and high-frequency TENS in post-episiotomy pain relief: a randomized,double-blind clinical trial

Objective

To evaluate the effectiveness of low-frequency TENS (LFT) and high-frequency TENS (HFT) in post-episiotomy pain relief.

Method

A randomized, controlled, double-blind clinical trial with placebo composed of 33 puerperae with post-episiotomy pain. TENS was applied for 30 minutes to groups: HFT(100 Hz; 100 µs), LFT (5 Hz; 100 µs), and placebo (PT). Four electrodes were placed in parallel near the episiotomy and four pain evaluations were performed with the numeric rating scale. The first and the second evaluation took place before TENS application and immediately after its removal and were done in the resting position and in the activities of sitting and ambulating. The third and fourth evaluation took place 30 and 60 minutes after TENS removal, only in the resting position. Intragroup differences were verified using the Friedman and Wilcoxon tests, and the intergroup analysis employed the Kruskal-Wallis test.

Results

In the intragroup analysis, there was no significant difference in the PT during rest, sitting, and ambulation (P>0.05). In the HFT and LFT, a significant difference was observed in all activities (P<0.001). In the intergroup analysis, there was a significant difference in the resting position in the HFT and LFT (P<0.001). In the sitting activity, a significant difference was verified in the second evaluation in the HFT and LFT (P<0.008). No significant difference was verified among the groups in ambulation (P<0.20).

Conclusions

LFT and HFT are an effective resource that may be included in the routine of maternity wards.     

Treatment of Headache by Transcutaneous Electrical Stimulation

SYNOPSIS
Transcutaneous electrical stimulation (TENS) has been used extensively for many types of pain but only rarely for headache. The object of this study was to judge the efficacy of TENS against placebo. Contrary to popular use, TENS (and placebo) were applied in a rigid manner, probably prejudicial to maximum effectiveness.
62 patients with migraine or muscle contraction headache, or both, were studied using TENS equipment of low amperage and high frequency. One of three modalities was chosen at random for each patient: TENS just above the patient's ability to perceive the stimuli (perceived stimuli), TENS just below the perception threshold (subliminal stimuli), and electrodes applied without electrical stimulation (placebo). Degree of improvement was judged by the patient using a scale of pain from 1 to 10. Following treatment with TENS perceived by the patient, 55% of patients noted improvement as compared to 18% after application of placebo; a significant difference (p < .025 chi-square test). Subliminal TENS was not statistically better than placebo.     

Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets

This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.     

Effect of Interferential Current Stimulation in Management of Osteo-arthritic Knee Pain

The primary purpose of this study was to assess the effect of interferential current stimulation on osteo-arthritic knee pain in the black Nigerian population.Thirty patients with a history of not less than three months' knee pain with radiographic confirmation of osteo-arthritis took part in the study. Patients were allocated alternately into an interferential current stimulation group and a placebo group.All the patients participated in a baseline exercise therapy programme with dietary advice. They received a total of eight 20-minute treatment sessions in four weeks. The treatment group received interferential current stimulation at a frequency of 100 Hz and pulse length of one-thirtieth of a second for the first 15 minutes of their treatment session. The stimulus was then reduced to 80 Hz for the next five minutes while other parameters remained unchanged. For the placebo group the electrodes of the stimulator were positioned appropriately but the stimulator was not tuned.The analysis of variance demonstrated a significant result (P < 0.01). Post hoc analysis revealed differences between initial and final pain values in the interferential current stimulation group. Similar results were observed in the placebo group, but the pain rating in the interferential current stimulation group was found to be significantly better than that for the placebo group.It was concluded that interferential current stimulation is more effective than a placebo in relieving osteo-arthritic knee pain in black Nigerian patients with symptomatic hypermobility.     

Metamizol and diclofenac profoundly reduce opioid consumption after minor trauma surgery

In the present work we investigate the analgesic combination of the pyrazole-derivative metamizol and the non-steroidal anti-inflammatory drug diclofenac after trauma surgery with respect to the postoperative opioid consumption (via patient-controlled analgesia (PCA)) in the first 24 h after surgery, and the reduction of pain in the immediate postoperative period. In a double-blind randomized placebo controlled study, 48 patients, scheduled for minor trauma surgery received either metamizol (three doses of 1 g intravenously) and diclofenac (two doses of 100 mg suppository) or placebo beginning immediately preoperatively and repeated postoperatively. Totally the verum group received metamizol 3 g and diclofenac 200 mg. Postoperative pain intensity was measured by the numeric rating scale (NRS). All patients were allowed to order levomethadone from a PCA-pump for 24 h after surgery. Pain scores and opioid consumption were evaluated in the first six postoperative hours, 12 and 24 h after end of surgery. The patients receiving verum had significantly less pain at all points in time except for 2 h and ordered a significantly lower cumulated dose of levomethadone during the first 24 h postoperatively than placebo treated subjects (opioid-sparing effect after 24 h: −74%). There were no significant differences in the incidence of side effects between the two groups. Perioperative application of metamizol and diclofenac results in better pain relief and significantly lowers opioid requirements in patients after minor trauma surgery.     

Effects of acupuncture and placebo TENS in addition to exercise in treatment of rotator cuff tendinitis

OBJECTIVE: To compare the effect of acupuncture with placebo transcutaneous electrical nerve stimulation (TENS) when added to the exercise treatment of rotator cuff tendinitis with respect to pain, shoulder movements and function. DESIGN: Prospective alternate allocation controlled trial. SETTING: Outpatient department. PATIENTS: Thirty-three patients (12 women and 21 men) were included in the study. All had clinically diagnosed rotator cuff tendinitis. INTERVENTION: Both groups underwent a standardized training programme. Each patient received in addition either 10 treatments with acupuncture or placebo TENS, 1-2 times per week. MAIN OUTCOME MEASURES: The parameters investigated were intensity of pain (measured with visual analogue scale), active, passive as well as functional movements in the shoulder (hand in neck (HIN) and pour out of a pot (POP)). Patients were tested before treatment, after treatment and at a six-month follow-up. Medicine intake, ability to lie on the affected side and sleep disturbances were evaluated. A subjective assessment was made after the treatment and at follow-up. RESULTS: Sixteen patients had acupuncture, 17 placebo TENS. Eight patients endured pain at rest in the placebo TENS group, and 10 in the acupuncture group. After treatment both groups improved, the improvement persisted at the six-month follow-up. Both groups increased range of movement. Except for the functional test HIN in the acupuncture group, there were no differences between the groups regarding other parameters investigated directly after treatment or at six-month follow-up. CONCLUSION: There is no difference between the effect of additional acupuncture treatment and placebo TENS in the treatment of rotator cuff tendinitis.     

Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation

Ten patients with pain due to osteoarthritis of the knee were treated in a double-blind cross-over study with two weeks of transcutaneous electrical nerve stimulation (TENS) and placebo. There was statistically significant pain relief by TENS and half of the patients chose to continue using TENS for pain control after the test month. However, at one year's follow-up, only two patients had sufficient benefit to continue using the device.     

Pain relief by applying transcutaneous electrical nerve stimulation (TENS) on acupuncture points during the first stage of labor: a randomized double-blind placebo-controlled trial

Transcutaneous electrical nerve stimulation (TENS) is one of the non-pharmacological means of pain relief for labor and delivery. We aimed to investigate the efficacy and safety of TENS on specific acupuncture points for reducing pain in the first stage of labor. In this double-blind, placebo-controlled trial, we randomly assigned healthy full-term parturients in active phase of first-stage labor to either TENS on four acupuncture points (Hegu [Li 4] and Sanyinjiao [Sp 6]) (n=52) or the TENS placebo (n=53). Visual analogue scale (VAS) was used to assess pain before and 30 and 60 min after treatment. The primary outcome was the rate of VAS score decrease 3 in each group. A questionnaire was given at 24h post-partum to evaluate the satisfaction of pain relieving method and the willingness to have the same treatment again. Mode of delivery and neonatal effect were measured as secondary outcome. One hundred women were eligible for analysis. TENS group experienced VAS score reduction 3 significantly more common than the TENS placebo group (31/50 [62%] vs 7/50 [14%], P<0.001). Willingness of using the same analgesic method for a future childbirth was also significantly different (TENS: 48/50 [96%] vs TENS placebo: 33/50 [66%], P<0.001). Operative delivery was increased in the TENS group (12/50 [24%] vs 4/50 [8%], P=0.05), but the neonatal outcomes were not different. The application of TENS on specific acupuncture points could be a non-invasive adjunct for pain relief in the first stage of labor.     

Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial

Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made.     

TENS and Pain Control after Coronary Artery Bypass Surgery

This paper describes a randomised controlled trial to evaluate the effectiveness of TENS in controlling pain following coronary artery bypass grafting (CABG). A total of 59 men undergoing CABG with internal mammary artery (IMA) at Bristol Royal Infirmary were randomly allocated to receive TENS or placebo in conjunction with patient-controlled analgesia (PCA) for one hour on their first postoperative day. A visual analogue pain score and the hourly usage of the PCA were recorded before, during and after the application of TENS or placebo. The results show that although pain scores were significantly reduced in the hour in which TENS was applied, there was no significant difference in this reduction between the TENS and placebo groups. PCA use by patients during the study period was limited, with the majority making none or one successful request per hour. The results imply that the observed reductions in pain were due to a placebo effect and that the use of TENS in conjunction with PCA following CABG with IMA is unlikely to confer a clinically important reduction in post-operative pain.     

Effect of transcutaneous electrical nerve stimulation characteristics on clinical pain

We compared the effects of four treatment variables on the pain reduction produced by transcutaneous electrical nerve stimulation and attempted to establish indications for TENS based on patient history and pain evaluation items. Treatment variables were the therapist and the three TENS stimulus characteristics--pulse width, frequency, and amplitude. We randomly assigned 192 consecutive adult patients suffering from painful conditions to one of four physical therapists and one of 12 stimulus characteristic combinations. We used a standard evaluation form that included a visual analog scale (VAS) to evaluate pain. Patients were given a 30-minute trial using TENS, followed by reevaluation. The VAS line length change after treatment was the criterion score for comparison of stimulus characteristic effectiveness. Although pain was reduced greatly with TENS (p = .01), a four-way analysis of variance (pulse width, frequency, amplitude, and therapist) attributed little of the treatment effect to the treatment variables or their interactions (r2 = .101). The amplitude effect, however, was borderline (p = .056), and subthreshold stimulation proved more effective than stimulation to tolerance (p = .05). Extensive multiple linear regression analyses failed to provide indications for TENS based on patient information and pain evaluation items. Therefore, pain remains the only indication for TENS, and we recommend subthreshold rather than higher amplitude stimulation on the initial TENS trial.     

Outcome of transcutaneous electrical nerve stimulation in chronic pain: short-term results of a double-blind, randomised, placebo-controlled trial

The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients’ satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients’ satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, x²=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.     

Pain relief by applying transcutaneous electrical nerve stimulation (TENS) during unsedated colonoscopy: A randomized double‐blind placebo‐controlled trial

Transcutaneous electrical nerve stimulation (TENS) is a noninvasive alternative to traditional pain treatments. TENS has been studied in the past as a pain reduction modality in colonoscopy with limited success. Reviews and meta‐analysis have shown that the inconclusive results of TENS may be due to the lack of randomized controlled trials and the difficulty in defining precise output parameters. The objective of this double‐blind randomized placebo‐controlled trial was to investigate the pain‐relieving effect of a new application of TENS in unsedated screening colonoscopy. Ninety patients undergoing unsedated screening colonoscopy were randomly allocated to one of three groups: a control group (n=30), a group to receive active TENS (n=30), or a group to receive placebo TENS (n=30). A visual analogue scale (VAS) and a five‐point Likert scale were used to assess pain 5min into the procedure and at the end of the procedure. The patient's bloating sensation during colonoscopy and the effect on the duration of the procedure were also evaluated. Throughout the procedure, the active TENS group experienced a VAS pain score reduction ≥50% compared to the placebo TENS group (P<0.001) and the control group (P<0.001). On the five‐point Likert scale, there was also a significant reduction in pain score in the active TENS group compared to the placebo TENS and control groups (P=0.009). No significant differences were found between the study groups as to the bloating sensation and the duration of the procedure. We conclude that TENS can be used as a pain relief therapy in unsedated screening colonoscopy.     

Transcutaneous electrical nerve stimulation versus oral analgesic: a randomized double-blind controlled study in acute traumatic pain

A double-blind controlled analgesic study was undertaken in outpatients suffering acute traumatic pain. One hundred patients completed the study and were randomly assigned to four treatment groups, each receiving either functioning transcutaneous electrical nerve stimulators (TENS), placebo TENS, acetaminophen with codeine and a functioning TENS, or acetaminophen with codeine and a placebo TENS. Pain was assessed prior to treatment, at 48 hours, and at one month using a visual analog scale. A statistically significant difference in pain relief occurred between the placebo and functioning TENS groups. The TENS was approximately as effective as acetaminophen (300-600 mg) with codeine (30-60 mg) but had no side effects. Transcutaneous electrical nerve stimulators have been shown to be effective in the management of acute traumatic pain and may be indicated for patients who cannot be given medications.     

Analgetische Effizienz von transkutaner elektrischer Nervenstimulation (TENS-Therapie) bei Patienten mit Gonarthrose

Background

The goal of the study was to substantiate the influence of TENS on pain development and medication needs of patients with proven gonarthrosis and chronic pain. The study included a 3-week stimulation period and 2-week observation period after the end of stimulation.

Materials and methods

Patients (at least 20 per group) were assigned to either an active treatment group or placebo group in a randomised, double-blind, placebo-controlled trial. For the active treatment group the TENS therapy device with HAN stimulation (alternating phase of stimulation) was used (TENStem eco®).Total length of time: 30 min at least two times a day. The length of therapy was 3 weeks (therapy), followed by an observation period of 2 weeks (follow-up). The total length of the study was 5 weeks, whereby at the beginning and at the end of weeks 1, 3 and 5 the SF-36, WOMAC score and Lysholm score were documented; the pain score was documented daily.

Results

There are no significant demographic differences between the groups. In the active treatment group there was clear relief in pain intensity in the morning, midday and evening over the 3-week period of therapy. The Lysholm score in the active treatment group was 53.4 at the beginning, 90 after 1 week, 94.5 after the third week and 91 by the fifth week (significant difference). There were no side effects.

Conclusion

TENS therapy with HAN stimulation resulted in pain relief in patients with gonarthrosis during the therapy period with TENS, but the pain relief did not last beyond the end of the TENS therapy. There was an improvement in the Lysholm score and the WOMAC score during the therapy. This improvement remained over the following 2-week period of observation without further TENS therapy. TENS therapy is a simple and effective method to treat gonarthrosis with very few side effects.     

Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain

OBJECTIVE: To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. STUDY DESIGN: Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. MAIN OUTCOME MEASURES: Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. RESULTS: The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (p<.001), but the reduction was negligible after placebo stimulation (to 96.7%, p = .786). In contrast, no significant change was found in the VASFR score (p = .666) and the flexion reflex area (p = .062) during and after stimulation within each group and between the two groups (p = .133 for VASFR and p = .215 for flexion reflex area). CONCLUSIONS: The same TENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.     

A randomized clinical trial of TENS and exercise for patients with chronic neck pain

OBJECTIVE: To investigate the effect of transcutaneous electrical nerve stimulation (TENS) on acupuncture points and neck exercise in chronic neck pain patients. DESIGN: A randomized clinical trial. SETTING: Hospital-based practice. SUBJECTS: Two hundred and eighteen patients with chronic neck pain. INTERVENTIONS: Subjects were randomized into three groups, receiving either (1) TENS over the acupuncture points plus infrared irradiation (TENS group); (2) exercise training plus infrared irradiation (exercise group); or (3) infrared irradiation alone (control); twice a week for six weeks. OUTCOME MEASURES: The values of verbal numeric pain scale, Northwick Park Neck Pain Questionnaire, and isometric neck muscle strength were assessed before, at the end of the six-week treatment, and at the six-month follow-up. RESULTS: Results demonstrated that after the six-week treatment, significant improvement in the verbal numerical pain scale was found only in the TENS group (0.60+/-2.54, p = 0.027) and the exercise group (1.57+/-2.67, p < 0.001). Though significant reduction in Northwick Park Neck Pain Questionnaire score was found in all three groups, post-hoc tests showed that both the TENS and the exercise group produced better improvement (0.38+/-0.60% and 0.39+/-0.62% respectively) than the control group (0.23+/-0.63%). Significant improvement (p = < 0.001 to 0.03) in neck muscle strength was observed in all three groups, however, the improvement in the control group was not clinically significant and it could not be maintained at the six-month follow-up. CONCLUSIONS: After the six-week treatment, patients in the TENS and exercise group had a better and clinically relevant improvement in disability, isometric neck muscle strength, and pain. All the improvements in the intervention groups were maintained at the six-month follow-up.