Comparing the Efficacy of Dorsal Root Ganglion Stimulation With Conventional Medical Management in Patients With Chronic Postsurgical Inguinal Pain: Post Hoc Analyzed Results of the SMASHING Study.

OBJECTIVES: Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients. MATERIALS AND METHODS: In this multicenter, randomized controlled study, DRG stimulation was compared with conventional medical management (CMM) (noninvasive treatments, such as medication, transcutaneous electric neurostimulation, and rehabilitation therapy) in patients with PSIP that was resistant to a neurectomy. Patients were recruited at a tertiary referral center for groin pain (SolviMáx, Eindhoven, The Netherlands) between March 2015 and November 2016. Suitability for implantation was assessed according to the Dutch Neuromodulation Association guidelines. The sponsor discontinued the study early owing to slow enrollment. Of 78 planned patients, 18 were randomized (DRG and CMM groups each had nine patients). Six patients with CMM (67%) crossed over to DRG stimulation at the six-month mark. RESULTS: Fifteen of the 18 patients met the six-month primary end point with a complete data set for a per-protocol analysis. Three patients with DRG stimulation had a negative trial and were lost to follow-up. The average pain reduction was 50% in the DRG stimulation and crossover group (from 6.60 ± 1.24 to 3.28 ± 2.30, p = 0.0029). Conversely, a 13% increase in pain was observed in patients with CMM (from 6.13 ± 2.24 to 6.89 ± 1.24, p = 0.42). Nine patients with DRG stimulation experienced a total of 19 adverse events, such as lead dislocation and pain at the implantation site. CONCLUSIONS: DRG stimulation is a promising effective therapy for pain relief in patients with PSIP resistant to conventional treatment modalities; larger studies should confirm this. The frequency of side effects should be a concern in a new study. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02349659.

Prospective Observational Cohort Study on Dorsal Root Ganglion Stimulation in Chronic Postsurgical Pain: Results of Patient-Reported Outcomes at Two Years.

OBJECTIVES: This study aimed to determine the long-term effects of dorsal root ganglion (DRG) stimulation on pain, physical function, and quality of life in patients with chronic postsurgical pain. We hypothesized that the effects of DRG stimulation would be sustainable through two years of follow-up. MATERIALS AND METHODS: This prospective observational cohort will include 30 patients, at least 18 years old, scheduled to receive DRG stimulation in two Dutch hospitals. A minimum pain score of 50 mm on a 100-mm visual analog scale was required. Following written informed consent, patients completed validated questionnaires on pain, physical function, and quality of life at baseline, one year, and two years. Change over time was analyzed using mixed model statistics, with Tukey-Kramer correction. A p-value of <0.05 was considered statistically significant. RESULTS: Follow-up was completed by 22 of 30 enrolled patients. Pain scores decreased at one year (-38 ± 7, 95% CI [-51 to -25], p < 0.001) and two years (-29 ± 6, 95% CI [-42 to -17], p < 0.001) compared with those at baseline. Physical function measured with pain severity and interference decreased at one and two years (-2.5 ± 0.5, 95% CI [-3.3 to -1.5], p < 0.001, and -2.3 ± 0.5, 95% CI [-3.3 to -1.3], p < 0.001, respectively). Quality of life increased over time (0.22 ± 0.05, 95% CI [11-33], p < 0.001, at one year; 0.21 ± 0.05, 95% CI [10-31], p = 0.001, at two years). CONCLUSIONS: DRG stimulation in chronic postsurgical pain is associated with a sustainable reduction in pain and an improvement in physical function and in quality of life, through two years of follow-up.

Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial.

BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21-24, a median change of -5·21 (-11·18 to -0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21-24 weeks (median change from baseline -4·08, -11·92 to -0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; -6·50, -10·83 to -0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2·42 (95% CI -5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage. INTERPRETATION: In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

A Comparison of 1000 Hz to 30 Hz Spinal Cord Stimulation Strategies in Patients with Unilateral Neuropathic Leg Pain Due to Failed Back Surgery Syndrome: A Multicenter, Randomized, Double-Blinded, Crossover Clinical Study (HALO).

INTRODUCTION: Multicenter, randomized, double-blinded crossover study. The Netherlands (ClinicalTrials.gov NCT02112474). We hypothesized that the pain suppressive effects of 1000 Hz and 30 Hz spinal cord stimulation (SCS) strategies are equally effective in patients with chronic, neuropathic, unilateral leg pain after back surgery. METHODS: Thirty-two patients (18-70 years, minimum leg pain 50 mm on 100 mm visual analog scale (VAS), minimal back pain) were randomized (1:1) to start 1000 Hz or 30 Hz neurostimulation for 9 days. After a 5-day washout, they crossed over, for another 9 days. Primary outcome was pain suppression (mean of VAS scores 4×/day) during the crossover period. The main investigators were blinded to strategy allocation, patients were blinded to the outcome, a blinded assessor analyzed the primary outcome. RESULTS: The primary outcome was analyzed in 26 patients. There was no period effect (delta 4 mm, p = 0.42, 95% CI [- 5, 13]), allowing direct intrapatient comparison of the treatment effect (delta 1 mm, p = 0.92, 95% CI [- 13, 14]). Ninety-two percent of patients in both periods experienced greater than 34% pain suppression (minimal clinically important difference, MCID). Secondary outcomes (22 patients): pain suppression and improved quality of life were sustained at 12 months; both were statistically significant and clinically relevant. Fifty percent of patients had greater than 80% pain suppression (p < 0.001). At study termination, all events were resolved; no unanticipated events were reported. Medtronic provided a grant for additional study costs. CONCLUSION: We conclude that our hypothesis regarding the effect of 1000 Hz and 30 Hz stimulation strategies on pain suppression was confirmed. Both stimulation strategies led to a large, sustainable, clinically relevant pain suppression and improvement in quality of life.

Prospective Cohort Analysis of DRG Stimulation for Failed Back Surgery Syndrome Pain Following Lumbar Discectomy.

INTRODUCTION: Surgical lumbar discectomy is a commonly performed routine spinal procedure that is usually undertaken to alleviate lumbar radicular symptoms caused by a herniated intervertebral disc. Surgical lumbar discectomy can also lead to chronic postsurgical leg and/or back pain (failed back surgery syndrome [FBSS]), a condition that can be refractory to conventional medical management. Early clinical results on the use of dorsal root ganglion (DRG) stimulation for FBSS have supported the use of this treatment alternative. METHODS: A multicenter, single-arm, observational cohort study enrolled patients who had chronic pain following surgical lumbar discectomy, had failed conservative treatments, and reported pain intensity of at least 6 out of 10 in the primary region of pain. Data were collected on pain, quality of life, disability, and mood at baseline and through 12 months. RESULTS: Thirteen patients underwent a trial of DRG stimulation; 11 (84.6%; 95% confidence interval = 57.8% to 95.7%) had good outcomes and underwent permanent device placement. Pain was reduced from a score of 8.64 (±0.92) at baseline to 2.40 (±2.38; n = 9) after 12 months of treatment, a 72.05% average reduction (P < 0.001). Similar improvements were observed across the secondary clinical measures, and safety data were in line with published rates. DISCUSSION: These results suggest that DRG stimulation induces pain relief in subjects diagnosed with FBSS. These reductions in pain were also associated with improvements in quality of life and disability. Additional prospective studies are warranted to further investigate this potential application of DRG stimulation, as well as to optimize patient selection, lead placement, and programming strategies.

Therapy-Related Explants After Spinal Cord Stimulation: Results of an International Retrospective Chart Review Study.

OBJECTIVES: Clinical trials of spinal cord stimulation (SCS) have largely focused on conversion from trial to permanent SCS and the first years after implant. This study evaluates the association of type of SCS and patient characteristics with longer-term therapy-related explants. MATERIALS AND METHODS: Implanting centers in three European countries conducted a retrospective chart review of SCS systems implanted from 2010 to 2013. Ethics approval or waiver was obtained, and informed consent was not required. The chart review recorded implants, follow-up visits, and date and reasons for any explants through mid-2016. Results are presented using Cox regression to determine factors associated with explant for inadequate pain relief. RESULTS: Four implanting centers in three countries evaluated 955 implants, with 8720 visits over 2259 years of follow-up. Median age was 53 years; 558 (58%) were female. Explant rate was 7.9% per year. Over half (94 of 180) of explants were for inadequate pain relief, including 32/462 (6.9%) of implants with conventional nonrechargeable SCS, 37/329 (11.2%) with conventional rechargeable and 22/155 (14.2%) with high-frequency (10 kHz) rechargeable SCS. A higher explant rate was found in univariate regression for conventional rechargeable (HR 1.98, p = 0.005) and high-frequency stimulation (HR 1.79, p = 0.035) than nonrechargeable SCS. After covariate adjustment, the elevated explant rate persisted for conventional rechargeable SCS (HR 1.95, p = 0.011), but was not significant for high-frequency stimulation (HR 1.71, p = 0.069). CONCLUSIONS: This international, real-world study found higher explant rates for conventional rechargeable and high-frequency SCS than nonrechargeable systems. The increased rate for conventional rechargeable stimulation persisted after covariate adjustment.

Altering Conventional to High Density Spinal Cord Stimulation: An Energy Dose-Response Relationship in Neuropathic Pain Therapy.

OBJECTIVES: To examine whether converting from conventional Spinal Cord Stimulation (SCS) to High Density (HD) SCS reduces neuropathic pain over a period of 12 months in patients with failed SCS therapy. METHODS: Retrospective, open label, single center, consecutive case series of 30 neuropathic pain patients (Failed Back Surgery Syndrome [FBSS], Complex Regional Pain Syndrome [CRPS], and polyneuropathy [NP]). Patients with an initial adequate response to conventional SCS, but in whom pain increased over time, were included (Numeric Rating Scales [NRS] >6). These patients were stimulated with HD-SCS parameters and followed-up for 12 months. We report pain intensity, measured with NRS, before SCS implantation, 1 and 3 months after starting SCS with conventional stimulation, and after 1, 6, and 12 months of HD SCS. RESULTS: Pain reduction with conventional stimulation was initially adequate (NRS mean 8.6 to 5.3 at three months postimplant) but increased over time to a mean NRS of 7.7 at the time of reprogramming. NRS scores decreased significantly to 4.3 (p = 0.015) after reprogramming from conventional SCS (30 Hz, 300 µsec, 3.0 V) to HD SCS (409 Hz, range 130-1000 Hz, 409 µsec, 2.4V) in the patients still using HD-SCS at 12 months. In the nonresponders (patients who stopped HD-SCS for any reason), 76% had a diagnosis of FBSS. Almost half of the patients aborting HD-SCS preferred to feel paresthesias despite better pain relief. There was a significant difference between nonresponders and responders regarding the amount of electrical energy delivered to the spinal cord. CONCLUSION: Neuropathic pain suppression is significantly enhanced after converting from failed conventional SCS to HD SCS in patients with FBSS, CRPS, and NP over a measured period of 12 months. There appears to be a dose-related response between the amount of energy delivered to the spinal cord and clinical effect.

Hygiene guideline for the planning, installation, and operation of ventilation and air-conditioning systems in health-care settings - Guideline of the German Society for Hospital Hygiene (DGKH).

Since the publication of the first "Hospital Hygiene Guideline for the implementation and operation of air conditioning systems (HVAC systems) in hospitals" (http://www.krankenhaushygiene.de/informationen/fachinformationen/leitlinien/12) in 2002, it was necessary due to the increase in knowledge, new regulations, improved air-conditioning systems and advanced test methods to revise the guideline. Based on the description of the basic features of ventilation concepts, its hygienic test and the usage-based requirements for ventilation, the DGKH section "Ventilation and air conditioning technology" attempts to provide answers for the major air quality issues in the planning, design and the hygienically safe operation of HVAC systems in rooms of health care.

Cost-effectiveness of minimal interventional procedures for chronic mechanical low back pain: design of four randomised controlled trials with an economic evaluation.

BACKGROUND: Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably resulting from single sources: facet, disc, sacroiliac joint or a combination of these. Usually, these minimal interventional procedures are an integral part of a multidisciplinary pain programme. A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown. The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic. METHODS: All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study. Patients with a suspected diagnosis of facet, disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis. If confirmed, they will be asked to participate in a randomized controlled trial (RCT). For each single source a separate RCT will be conducted. Patients with a combination of facet, disc or sacroiliac joint problems will be invited for participation in a RCT as well. An economic evaluation from a societal perspective will be performed alongside these four RCTs. Patients will complete questionnaires at baseline, 3 and 6 weeks, 3, 6, 9 and 12 months after start of the treatment. Costs will be collected using self-completed cost questionnaires. DISCUSSION: No trials are yet available which have evaluated the cost-effectiveness of minimal interventional procedures in patients with chronic mechanical low back pain, which emphasizes the importance of this study. TRIAL REGISTRATION NUMBER: National Trial Register: NTR3531.

Time trends of mercury in feathers of West Greenland birds of prey during 1851-2003.

Temporal trends of mercury (Hg) in West Greenland gyrfalcons, peregrine falcons, and white-tailed eagles were determined over 150 years from 1851 to 2003. Hg was measured in the fifth primary feather. Results showed that Hg increased in the order gyrfalcon (lowest) < peregrine falcon (intermediate) < white-tailed eagle (highest). All species showed significant age accumulations, which were taken into account in the temporal trend analysis. Of eight time trend analyses (three species and three age groups of which one was missing), seven showed an increase in primary feather concentrations. Of these, four were significant at the 5% level, two were close to being significant, and one was not significant. The linear regressions of which three out of four showed significant increases were for juvenile and immature gyrfalcon and juvenile peregrine falcon, which covered only periods prior to 1960, owing to limited data from the last half-century. The two sample comparisons of Hg 10-year medians for adult peregrine falcons and juvenile and adult white-tailed eagles indicated a continued increase during recent decades. However, low levels of Hg in a few recent collections among gyrfalcons and peregrines could indicate a change in the increasing trend.

Mortality factors, environmental contaminants, and parasites of white-tailed sea eagles from Greenland.

Twelve white-tailed sea eagles (Haliaeetus albicilla groenlandicus) found dead between 1997 and 2000 in Greenland were examined to investigate the health status, including the causes of death and the burden of organochlorine contaminants and potentially toxic heavy metals. The determined causes of death were unspecific trauma (n = 6), lead poisoning (n = 2) with 36 and 26 ppm lead in the liver tissue, infectious diseases (n = 1), injuries sustained during intraspecific conflict (n = 1), and gunshot (n = 1). One lead poisoned eagle had a single lead shot pellet in its gizzard. No diagnosis could be made in one case because of decomposition of the carcass. Four of the investigated eagles were injured with lead shot or bullet fragments; one of the birds was killed with about 69 lead shots. Levels of organochlorine pesticides, polychlorinated biphenyls, mercury, and cadmium in organs were moderate. The parasite fauna consisted of one coccidian and three helminth species. The acanthocephalas Profiliocollis botulus and Corynosoma suduche as well as the nematode Stegophorus stellaepolaris are all new records for the white-tailed sea eagle.

Paravertebral blockade for minor breast surgery.

UNLABELLED: Paravertebral blockade (PVB) has been advocated as a useful technique for breast surgery. We prospectively compared the efficacy of PVB via a catheter technique with the efficacy of general anesthesia (GA) for minor breast surgery. Thirty patients were randomized into two groups to receive either PVB or GA. Variables of efficacy were postoperative pain measured on a visual analog scale, postoperative nausea and vomiting (PONV), recovery time, and patient satisfaction. Postoperative visual analog scale scores in the PVB group were significantly lower in the early postoperative period (maximum, 12 vs 45 mm; P < 0.01). In both groups, PONV was nearly absent. There was no difference in recovery time. Patient satisfaction was better in the PVB group (2.8 vs 2.3; scale, 0-3; P < 0.01). There was one inadvertent epidural block and one inadvertent pleural puncture in the PVB group. Although PVB resulted in better postoperative pain relief, the advantages over GA were marginal in this patient group because postoperative pain was relatively mild and the incidence of PONV was small. Considering that the technique has a certain complication rate, we conclude that at present the risk/benefit ratio of PVB does not favor routine use for minor breast surgery. IMPLICATIONS: This study confirms the previously reported superior pain relief after paravertebral blockade (PVB) for breast surgery. However, considering the relatively mild postoperative pain and therefore the limited advantage of PVB for these patients, the risk/benefit ratio does not favor the routine use of PVB for minor breast surgery.