Brian F. Degenhardt

Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: review of the available pre-clinical data, and first human studies.

The endogenous cannabimimetic compound, and anandamide analogue, N-palmitoyl-ethanolamine (PEA), was shown to exert potent anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic and inflammatory pain by acting via several possible mechanisms. However, only scant data have been reported on the regulation of PEA levels during pathological conditions in animals or, particularly, humans. We review the current literature on PEA and report the results of three separate studies indicating that its concentrations are significantly increased during three different inflammatory and neuropathic conditions, two of which have been assessed in humans, and one in a mouse model. In patients affected with chronic low back pain, blood PEA levels were not significantly different from those of healthy volunteers, but were significantly and differentially increased (1.6-fold, P<0.01, N=10 per group) 30 min following an osteopathic manipulative treatment. In the second study, the paw skin levels of PEA in mice with streptozotocin-induced diabetic neuropathic pain were found to be significantly higher (1.5-fold, P<0.005, N=5) than those of control mice. In the third study, colonic PEA levels in biopsies from patients with ulcerative colitis were found to be 1.8-fold higher (P<0.05, N=8-10) than those in healthy subjects. These heterogeneous data, together with previous findings reviewed here, substantiate the hypothesis that PEA is an endogenous mediator whose levels are increased following neuroinflammatory or neuropathic conditions in both animals and humans, possibly to exert a local anti-inflammatory and analgesic action.

Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial

BackgroundThe Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) is a registered, double-blinded, randomized, controlled trial designed to assess the efficacy of osteopathic manipulative treatment (OMT) as an adjunctive treatment in elderly patients with pneumonia.Methods406 subjects aged ≥ 50 years hospitalized with pneumonia at 7 community hospitals were randomized using concealed allocation to conventional care only (CCO), light-touch treatment (LT), or OMT groups. All subjects received conventional treatment for pneumonia. OMT and LT groups received group-specific protocols for 15 minutes, twice daily until discharge, cessation of antibiotics, respiratory failure, death, or withdrawal from the study. The primary outcomes were hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score.ResultsIntention-to-treat (ITT) analysis (n = 387) found no significant differences between groups. Per-protocol (PP) analysis (n = 318) found a significant difference between groups (P = 0.01) in LOS. Multiple comparisons indicated a reduction in median LOS (95% confidence interval) for the OMT group (3.5 [3.2-4.0] days) versus the CCO group (4.5 [3.9-4.9] days), but not versus the LT group (3.9 [3.5-4.8] days). Secondary outcomes of duration of intravenous antibiotics and treatment endpoint were also significantly different between groups (P = 0.05 and 0.006, respectively). Duration of intravenous antibiotics and death or respiratory failure were lower for the OMT group versus the CCO group, but not versus the LT group.ConclusionsITT analysis found no differences between groups. PP analysis found significant reductions in LOS, duration of intravenous antibiotics, and respiratory failure or death when OMT was compared to CCO. Given the prevalence of pneumonia, adjunctive OMT merits further study.

Palpatory Accuracy of Lumbar Spinous Processes Using Multiple Bony Landmarks

OBJECTIVE Accurate localization of vertebral segments is crucial for many treatment procedures. The objective of this study was to determine accuracy of identification of lumbar spinous process levels by palpation. METHODS Three examiners independently identified the spinous processes of L1-L4 on 60 prone volunteers using multiple bony landmarks including the sacral base, L5, Tuffiers line, T12, and the 12th ribs. The spinous processes were marked with radiopaque skin markers. Location of marker placement and presence of anatomical anomalies were determined by posteroanterior lumbar radiographs. Accuracy of marker placement and interobserver reliability were assessed using weighted κ values. Generalized linear mixed models and Cochran-Mantel-Haenszel tests assessed the relationship of accuracy to training level, presence of anatomical anomalies, and participant characteristics. RESULTS Examiners identified a spinous process in 91% of vertebral assessments. Correct identification of vertebral level occurred 69% of the time (κ = 0.81; 95% confidence interval, 0.79-0.83). Faculty examiners were significantly more accurate in identifying the correct vertebral level than the resident examiner (67%-78% vs 51%, P ≤ .03). The presence of 12th rib anomalies decreased accuracy for all examiners (P ≤ .05), reducing accuracy from 74% to 55%. Accuracy was higher in male participants than in female participants (P = .01). Obesity significantly decreased accuracy (P = .0003) at L3 (50% vs 73%) and L4 (44% vs 72%). CONCLUSIONS Identification of lumbar spinous processes using multiple landmarks was more accurate than previously reported values. However, accuracy was dependent on examiner experience, presence of anatomical anomalies, and participant characteristics.

Reliability of Tuffierʼs Line as an Anatomic Landmark

Study Design. The level of Tuffiers line was assessed on 200 standing and 60 prone lumbar radiographs. Sex, height, weight, and body mass index (BMI) were correlated with the radiograph findings. Objective. To determine whether the level of Tuffiers line is associated with sex, height, weight, or BMI. Summary of Background Data. Tuffiers line (intercristal line) is a commonly used landmark for identification of the L4–L5 interspace; however, multiple studies have identified that this landmark is unreliable. Methods. The level of Tuffiers line was assessed retrospectively on 200 standing anteroposterior lumbar radiographs and correlated with sex. Prospectively, the level of Tuffiers line was assessed on 60 prone posteroanterior lumbar radiographs and correlated with sex, height, weight, and BMI. Results. In men, the intercristal line most often intersected the L4 body or inferior endplate. In women, the intercristal line most often intersected the L5 body or superior endplate. Weight and BMI had no correlation with Tuffiers line. Subjects with a Tuffiers line through L4 were taller than those with a Tuffiers line through L5. Conclusion. Tuffiers line demonstrated predictable sex-related differences: men had an intercristal line that most often intersected the L4 body or inferior endplate whereas the womens intercristal line most often intersected the L5 body or superior endplate. However, because the actual level of Tuffiers line may vary from the L4 body to the L5 body, the intercristal line is insufficient to use as the sole landmark for assessing spinal segmental level.

Preliminary findings on the use of osteopathic manipulative treatment: outcomes during the formation of the practice-based research network, DO-Touch.NET.

CONTEXT Few studies have assessed the use of osteopathic manipulative treatment (OMT) and subsequent patient-reported outcomes. OBJECTIVE To assess the current use of OMT and associated patient-reported outcomes. DESIGN A retrospective medical record review and a prospective observational study. SETTING Two university-based sites and their clinics associated with the practice-based research network DO-Touch.NET. PARTICIPANTS Patients aged 18 years or older who received OMT. MAIN OUTCOME MEASURES Medical records from 2007 were retrospectively reviewed to identify conditions being managed with OMT. From 2008 to 2010, patients were recruited before seeing their physicians. Questionnaires were distributed to patients and physicians, and information including demographics, chief complaints, symptom severity, current and past treatments, interference of symptoms with quality of life, physical examination findings, diagnoses, OMT performed, and immediate patient response to OMT was collected. A subset of patients provided data on symptom severity and frequency and other treatments daily for the 7 days after OMT. On day 7, symptom interference with quality of life was reassessed. RESULTS Retrospective data were collected from 2569 office visits, and prospective data were collected from 299 office visits (patient age range, 18-93 years). In the medical record review, 17 of the top 25 diagnoses (68%) were related to musculoskeletal conditions. In the prospective study, 18 of the top 24 medical diagnoses (75%) were related to musculoskeletal conditions. Immediately after OMT, patients at 271 of 296 office visits (92%) felt better or much better; those at 5 (<2%) felt worse. After 7 days, patients at 126 of 175 office visits (72%) felt better or much better, and those at 10 (6%) felt worse. Average and worst symptom severity decreased until post-OMT days 4 and 5, respectively, when severity leveled off. There was decreased interference of symptoms with quality of life from before OMT to 7 days after OMT in usual/general activities, sleep, mood, and relationships (all P≤.05). CONCLUSION These preliminary results suggest that for adults, OMT is predominantly used for managing musculoskeletal pain conditions and is effective for short-term symptom relief. Continued surveillance of DO-Touch.NET member practice outcomes may help identify priorities for osteopathic research and define evidence-based standards for OMT practice and training.

Assessment of skin blood flow following spinal manual therapy: A systematic review

Skin blood flow (SBF) indexes have been used to describe physiological mechanisms associated with spinal manual therapy (SMT). The aims of the current review were to assess methods for data collection, assess how investigators interpreted SBF changes, and formulate recommendations to advance manual medicine research. A database search was performed in PubMed, Cochrane Library, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature through April 2014. Articles were included if at least 1 outcome measure was changes in 1 SBF index following SMT. The database search yielded 344 records. Two independent authors applied the inclusion criteria. Twenty studies met the inclusion criteria. Selected studies used heterogeneous methods to assess short-term post-SMT changes in SBF, usually vasoconstriction, which was interpreted as a general sympathoexcitatory effect through central mechanisms. However, this conclusion might be challenged by the current understanding of skin sympathetic nervous activity over local endothelial mechanisms that are specifically controlling SBF. Evaluation of SBF measurements in peripheral tissues following SMT may document physiological responses that are beyond peripheral sympathetic function. Based on the current use of SBF indexes in clinical and physiological research, 14 recommendations for advancing manual medicine research using laser Doppler flowmetry are presented.

Changes in Cytokines, Sensory Tests, and Self-Reported Pain Levels After Manual Treatment of Low Back Pain.

Study Design: Unbalanced 3-factor design with repeated measures on 1 factor. Objective: To determine the effect of manual treatment (MT) on cytokine and pain sensations in those with and without low back pain (LBP). Summary of Background Data: Evidence suggests that MT reduces LBP but by unknown mechanisms. Certain cytokines have been elevated in patients with LBP and may be affected by MT. Methods: Participants aged 20–60 years with chronic LBP or without LBP were recruited and randomly assigned to MT, sham ultrasound treatment, or no treatment groups. Venous blood samples were collected and pain levels assessed at baseline, 1 hour later, and 24 hours later. Blood was analyzed for interleukin (IL)-1&bgr;, IL-6, tumor necrosis factor-&agr;, and C-reactive protein. Pain levels were measured by pressure pain threshold (PPT), mechanical detection threshold (MDT), dynamic mechanical allodynia, and self-report. Results: Forty (30 women, age 36±11 y) participants completed the study, 33 with LBP (13 MT, 13 sham ultrasound treatment, and 7 no treatment) and 7 without LBP. Participants with or without LBP could not be differentiated on the basis of serum cytokine levels, PPT, or MDT (P≥0.08). There were no significant differences between the groups at 1 hour or 24 hours on serum cytokines, PPT, or MDT (P≥0.07). There was a significant decrease from baseline in IL-6 for the no treatment (LBP) group (P=0.04), in C-reactive protein for the sham ultrasound treatment group (P=0.03), in MDT for all 3 LBP groups (P⩽0.02), and in self-reported pain for the MT and sham ultrasound treatment groups (P=0.03 and 0.01). Conclusions: Self-reported pain was reduced with MT and sham ultrasound treatment 24 hours after treatment, but inflammatory markers within venous circulation and quantitative sensory tests were unable to differentiate between study groups. Therefore, we were unable to characterize mechanisms underlying chronic LBP.

Multicenter Osteopathic Pneumonia Study in the Elderly: Subgroup Analysis on Hospital Length of Stay, Ventilator-Dependent Respiratory Failure Rate, and In-hospital Mortality Rate

CONTEXT Osteopathic manipulative treatment (OMT) is a promising adjunctive treatment for older adults hospitalized for pneumonia. OBJECTIVE To report subgroup analyses from the Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) relating to hospital length of stay (LOS), ventilator-dependent respiratory failure rate, and in-hospital mortality rate. DESIGN Multicenter randomized controlled trial. SETTING Seven community hospitals. PARTICIPANTS Three hundred eighty-seven patients aged 50 years or older who met specific criteria for pneumonia on hospital admission. INTERVENTIONS Participants were randomly assigned to 1 of 3 groups that received an adjunctive OMT protocol (n=130), a light touch (LT) protocol (n=124), or conventional care only (CCO) (n=133). MAIN OUTCOME MEASURES Outcomes for subgroup analyses were LOS, ventilator-dependent respiratory failure rate, and in-hospital mortality rate. Subgroups were age (50-74 years or ≥75 years), Pneumonia Severity Index (PSI) class (I-II, III, IV, or V), and type of pneumonia (community-acquired or nursing-home acquired). Data were analyzed by intention-to-treat and per-protocol analyses using stratified Cox proportional hazards models and Cochran-Mantel-Haenszel tests for general association. RESULTS By per-protocol analysis of the younger age subgroup, LOS was shorter for the OMT group (median, 2.9 days; n=43) than the LT (median, 3.7 days; n=45) and CCO (median, 4.0 days; n=65) groups (P=.006). By intention-to-treat analysis of the older age subgroup, in-hospital mortality rates were lower for the OMT (1 of 66 [2%]) and LT (2 of 68 [3%]) groups than the CCO group (9 of 67 [13%]) (P=.005). By per-protocol analysis of the PSI class IV subgroup, the OMT group had a shorter LOS than the CCO group (median, 3.8 days [n=40] vs 5.0 days [n=50]; P=.01) and a lower ventilator-dependent respiratory failure rate than the CCO group (0 of 40 [0%] vs 5 of 50 [10%]; P=.05). By intention-to-treat analysis, in-hospital mortality rates in the PSI class V subgroup were lower (P=.05) for the OMT group (1 of 22 [5%]) than the CCO group (6 of 19 [32%]) but not the LT group (2 of 15 [13%]). CONCLUSION Subgroup analyses suggested adjunctive OMT for pneumonia reduced LOS in adults aged 50 to 74 years and lowered in-hospital mortality rates in adults aged 75 years or older. Adjunctive OMT may also reduce LOS and in-hospital mortality rates in older adults with more severe pneumonia. Interestingly, LT also reduced in-hospital mortality rates in adults aged 75 years or older relative to CCO. (ClinicalTrials.gov number NCT00258661).

The National Osteopathic Research Center at the University of North Texas Health Science Center: Inception, Growth, and Future

The osteopathic profession has long recognized the need to carry out research in order to improve clinical care. Osteopathic physicians have a particular obligation to carry out research in areas, such as osteopathic manipulative medicine (OMM), that are unique to osteopathic medicine. OMM is similar to manual therapy that is performed by other types of practitioners, but it has some distinctive characteristics. Osteopathic doctors also use OMM to treat infectious disease-not just musculoskeletal disorders.In 2001, several osteopathic professional organizations agreed to jointly fund a national osteopathic research center at one of the osteopathic medical colleges. Five osteopathic colleges submitted research proposals in response to a request for applications. The University of North Texas Health Science Center (UNTHSC) was chosen to be the site for the Osteopathic Research Center (ORC) and was funded for four years with

Characterizing Adverse Events Reported Immediately After Osteopathic Manipulative Treatment

1.1M. Between 2002 and 2007, the ORC received an additional