Cost-Effectiveness of Radiofrequency Denervation for Patients With Chronic Low Back Pain:The MINT Randomized Clinical Trials

OBJECTIVES: To evaluate the cost-effectiveness of radiofrequency denervation when added to a standardized exercise program for patients with chronic low back pain. METHODS: An economic evaluation was conducted alongside 3 pragmatic multicenter, nonblinded randomized clinical trials (RCTs) in The Netherlands with a follow up of 52 weeks. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain; a positive diagnostic block at the facet joints (n = 251), sacroiliac (SI) joints (n = 228), or a combination of facet joints, SI joints, and intervertebral discs (n = 202); and were unresponsive to initial conservative care. Quality-adjusted life-years (QALYs) and societal costs were measured using self-reported questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to estimate statistical uncertainty. RESULTS: After 52 weeks, no difference in costs between groups was found in the facet joint or combination RCT. The total costs were significantly higher for the intervention group in the SI joint RCT. The maximum probability of radiofrequency denervation being cost-effective when added to a standardized exercise program ranged from 0.10 in the facet joint RCT to 0.17 in the SI joint RCT irrespective of the ceiling ratio, and 0.65 at a ceiling ratio of €30 000 per QALY in the combination RCT. CONCLUSIONS: Although equivocal among patients with symptoms in a combination of the facet joints, SI joints, and intervertebral discs, evidence suggests that radiofrequency denervation combined with a standardized exercise program cannot be considered cost-effective from a societal perspective for patients with chronic low back pain originating from either facet or SI joints in a Dutch healthcare setting

Health care expenditure and GDP: An international panel smooth transition approach

In this paper, we investigate the potential threshold effects in the relationship between national expenditures on health care and national income. Using a panel threshold regression model, we derive country-specific and time-specific income elasticities for 17 OECD countries over the period 1975–2003. In contrast to many previous analyses, our empirical results show that health care is a necessity rather than a luxury. Further, the relationship between health expenditure and income seems rather nonlinear, changing over time and across countries

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

Genetic Control of a Central Pattern Generator: Rhythmic Oromotor Movement in Mice Is Controlled by a Major Locus near Atp1a2

Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo

Bilateral Brainstem Connections of the Rat Supratrigeminal Region

Efferent and afferent connections of the supratrigeminal region were studied in the rat using iontopho-retically delivered horseradish peroxidase and Phaseolus vulgaris leuco-agglutinin. Projections of supratrigeminal efferents were found to the contralateral supratrigeminal region, to the ipsi- and contralateral trigeminal motor nuclei and the medullary reticular formation, and to the ipsilateral facial and hypoglossal motor nuclei. Neurons projecting to the supratrigeminal region were located in the contralateral supratrigeminal nucleus, in the ipsilateral mesencephalic trigeminal nucleus and bilaterally in the medullary reticular formation. This organization is discussed with respect to bilateral oral motor control mechanism

Arrangement and Connections of Mesencephalic Trigeminal Neurons in the Rat

The morphology of the mesencephalic trigeminal nucleus was examined microscopically in serial frozen sections. The nucleus extends over a length of about 4.5 mm, and its cell number was calculated to range from 1,000 to 1,600. 60% of the cells were located in the caudal third of the nucleus. Clustering of large unipolar cells was seen throughout the nucleus. Small spindle-shaped multipolar cells were found in the pontine part of the nucleus. The efferent connections of the mesencephalic trigeminal neurons were investigated by means of iontophoretically delivered Phaseolus vulgaris leuco-agglutinin or horseradish peroxidase after electrophysiological identification of mesencephalic trigeminal neurons. All projections were found ipsilateral to the injection site; they were confined to the trigeminal motor nucleus, especially to its lateral part, and to the dorsolateral reticular formation. The latter projection area included the supratrigeminal nucleus, the nucleus of Probst, and the parvocellular reticular zone. There were no direct projections to the facial or hypoglossal motor nuclei. It is concluded that proprioceptive input from one side is mediated polysynaptically to the bilateral oral final common-path neurons, with the exception of the ipsilateral trigeminal motoneuron

Masseter, Digastric and Omohyoidal Responses from Weak Mechanical Oral Stimuli in the Chewing Rat

In rats anesthetized with ketamine, effects of jaw jerks (rise time 5 ms, strength 70 mN) applied in the open direction were studied both in the quiescent preparation and during rhythmic jaw-opening and jaw-closing movements (induced by mechanical stimulation of the palate). The left masseter, posterior and anterior digastric and omohyoid muscles were fitted with electrodes for recording electromyographic responses. In the quiescent state a jaw jerk causes responses in all recorded muscles. In the rhythmic preparation masseter responses persisted but digastric and omohyoidal responses were suppressed. This suppression was most prominent when jerks were applied during closing. However, responses in digastrics and omohyoid persisted when masseter nerves and periodontal afferents of the lower incisors were blocked with xylocaine. The suppression of digastric and omohyoidal responses therefore originates – at least partly – from masseter and periodontal afferents. When the periodontal afferents alone were blocked with xylocaine only the response in the opening phase persisted. The suppression of digastric and omohyoidal responses during opening are therefore reflexes from periodontal receptors. These observations support the concept that oral activity is controlled by two relatively independent systems. The first program-oriented system generates the basic movements whereas the second, environment-oriented, system has access to the program for correcting perturbations. There is evidence that muscles poorly supplied with muscle spindles (digastrics and omohyoid) act as pure effectors. Modulation of their activity is prompted by exteroceptors and muscle receptors in the masticatory muscles

A hierarchy of neural control of mastication in the rat

In rats anaesthetized with ketamine, rhythmic jaw-opening and jaw-closing movements were induced by palatal stimulation. The two masseter muscles (jaw-closing) and the four digastric muscles (jaw-opening) were fitted with electrodes, which could be used either for electrical stimulation or for recording electromyographic responses. Electrical stimulation of the masseters in the phase when the digastrics were the contracting muscles, caused responses in the digastrics. The amplitude of these responses was dependent on whether the stimulated masseters were active or not. The responses in digastric persisted when contraction of the masseters during stimulation was prevented by dantrolene sodium but they disappeared when the masseteric nerves were blocked with xylocain. The responses in digastric are thus reflexes from stimulating afferent fibres in the masseteric nerves. Likewise, electrical stimulation of the four digastrics in the phase when the masseters were contracting, caused responses in the masseters. The amplitude of these responses, however, was independent of the state of activity of the stimulated digastrics. Furthermore, the responses in masseter disappeared when contraction of the digastrics was prevented by dantrolene sodium; but they persisted when the digastric nerves were blocked with xylocain, provided the digastrics continued to twitch to the electric stimuli. The responses in masseter are thus reflexes in masseter caused by mechanical stretch transmitted from the digastric twitche