Changes in pain and quality of life in depressed individuals with spinal cord injury: does type of pain matter?

OBJECTIVE: To examine the association of neuropathic and nociceptive pain severity and interference with quality of life (QoL) in persons with spinal cord injury (SCI) who underwent a randomized controlled 12-week trial of an antidepressant to treat depression. A secondary objective was to assess the effect of changes in pain on mobility and physical independence. DESIGN: Multivariable ANCOVA models controlling for relevant demographic covariates, treatment condition, and baseline pain and QoL were used. SETTING: Six rehabilitation centers. PARTICIPANTS: Of the 133 persons who were randomized into the trial, 108 provided pain severity and interference ratings through follow-up. INTERVENTIONS: Not applicable. OUTCOME MEASURES: The Satisfaction with Life Scale and the physical and mental component summary scores of the 12-Item Short-Form Health Survey (SF-12). Secondary outcome measures included the mobility and physical independence subscales of the Craig Handicap Assessment and Reporting Technique (CHART). RESULTS: Broadly, few associations between pain and QoL were evident. Results revealed relationships between lower baseline nociceptive pain interference and higher satisfaction with life and mental health-related QoL at 12 weeks. Similarly, lower neuropathic pain interference was associated with change in physical independence, but unrelated to mobility. CONCLUSIONS: Pain interference over time may be differentially related to QoL outcomes based on the type of pain following SCI, but overall, there were no extensive relationships between pain and QoL in this sample of depressed persons with SCI.

Assessing the prevalence of autoimmune, endocrine, gynecologic, and psychiatric comorbidities in an ethnically diverse cohort of female fibromyalgia patients: does the time from hysterectomy provide a clue?

BACKGROUND: This retrospective chart review investigated differences in the prevalence of medical comorbidity between women with fibromyalgia (FM) (n=219) and a control group women with chronic pain (CP) without FM (n=116). The specific aims were to compare the prevalence of autoimmune, psychiatric, endocrine, gynecologic pathology, the relationship between timing of gynecologic surgery, and pain onset. We additionally sought to compare the number of comorbidities in an ethnically diverse cohort. METHODS: This was a retrospective chart review of patients seen in FM or CP clinics at an academic medical center in 2009-2010. RESULTS: Logistic regression modeling found that gynecologic, endocrine, and autoimmune diagnoses were independently associated with a diagnosis of FM. Detailed analyses showed that thyroid disease (P<0.01) and gynecologic surgery (P<0.05) were significantly more common in FM. Women with FM were more likely to have multiple autoimmune, endocrine, gynecologic, or psychiatric pathologies. A relationship was observed between the timing of gynecologic surgery and pain onset in FM, with more surgeries observed in the years just prior to pain onset or in the year after pain onset. A similar pattern was not found in the control group. CONCLUSION: This study demonstrates that autoimmune, endocrine, and gynecologic pathologies occur more commonly in women with FM than in those with CP, which is consistent with findings in less ethnically diverse samples. Moreover, a relationship was found between timing of pain onset and gynecologic surgery. A larger prospective study of the relationship between gynecologic surgery and pain onset in FM is warranted.

The Cost-Utility of Total Hip Arthroplasty: Earlier Intervention, Improved Economics.

We estimated the cost of Quality-Adjusted-Life-Years gained according to preoperative disease severity. We studied 159 primary unilateral THA, mean follow-up: 4 years. A median split of preoperative WOMAC scores was done to set apart a low (better) and a high (worse) score group. The groups with worse preoperative WOMAC were consistently associated with a less cost-effective intervention. The highest mean cost-effectiveness was achieved by patients with better WOMAC-total ($8256.32/QALY-gained). As patients aged, the cost-effectiveness of THA decreased. Patients 75 years of age or older and with worse scores had the least cost-effective interventions ($25,937.33/QALY-gained). THA remains a very cost-effective intervention even when performed in older "sicker" patients. Waiting for the patient to deteriorate will make the intervention more "expensive".

Venlafaxine extended-release for depression following spinal cord injury: a randomized clinical trial.

IMPORTANCE: Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury (SCI). Antidepressants are used routinely to treat depression, yet no placebo-controlled trials have been published in this population to our knowledge. OBJECTIVE: To determine the efficacy and tolerability of venlafaxine hydrochloride extended-release (XR) for major depressive disorder (MDD) or dysthymic disorder in persons with chronic SCI. DESIGN, SETTING, AND PARTICIPANTS: Multisite, randomized (1:1), double-blind, placebo-controlled Project to Improve Symptoms and Mood After SCI (PRISMS) trial. All research staff conducting screening, intervention, and outcome procedures were blinded to randomization status. We screened 2536 patients from outpatient clinics at 6 SCI treatment centers in the United States and randomized 133 participants into the trial. Participants were 18 to 64 years old and at least 1 month after SCI, with MDD or dysthymic disorder. Seventy-four percent of participants were male, and participants were on average 40 years old and 11 years after SCI. Forty-seven percent had cervical injuries, 53.4% had American Spinal Injury Association injury severity A (complete injury) SCI, 24.1% had at least 2 prior MDD episodes, and 99.2% had current MDD. Common comorbidities included chronic pain (93.9%), significant anxiety (57.1%), and history of substance dependence (44.4%). INTERVENTIONS: Twelve-week trial of venlafaxine XR vs placebo using a flexible-dose algorithm. MAIN OUTCOMES AND MEASURES: The Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks. RESULTS: Mixed-effects models revealed a significant difference between the venlafaxine XR and placebo groups in improvement on the Maier subscale from baseline to 12 weeks (treatment effect, 1.6; 95% CI, 0.3-2.9; P = .02) but not on the HAM-D 17-item version (treatment effect, 1.0; 95% CI, -1.4 to 3.4; P = .42). Participants receiving venlafaxine XR reported significantly less SCI-related disability on the Sheehan Disability Scale at 12 weeks compared with placebo (treatment effect, 4.7; 95% CI, 1.5-7.8; P = .005). Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine XR group compared with the placebo group over 12 weeks. CONCLUSIONS AND RELEVANCE: Venlafaxine XR was well tolerated by most patients and an effective antidepressant for decreasing core symptoms of depression and improving SCI-related disability. Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic SCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00592384.

Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression: a randomized, controlled trial.

OBJECTIVES: To (1) determine the efficacy of venlafaxine XR for the treatment of pain (secondary aim) in individuals with spinal cord injury (SCI) enrolled in a randomized controlled trial (RCT) on the efficacy of venlafaxine XR for major depressive disorder (MDD) (primary aim); and (2) test the hypothesis that venlafaxine XR would be effective for both neuropathic and nociceptive pain. DESIGN: Multisite, double-blind, randomized (1:1) controlled trial with subjects block randomized and stratified by site, lifetime history of substance abuse, and prior history of MDD. SETTING: Six Departments of Physical Medicine and Rehabilitation in university-based medical schools. PARTICIPANTS: Individuals (N=123) with SCI and major depression between 18 and 64 years of age, at least 1 month post-SCI who also reported pain. INTERVENTION: Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule. OUTCOME MEASURES: A 0-to-10 numeric rating scale for pain, pain interference items of the Brief Pain Inventory; 30% and 50% responders. RESULTS: The effect of venlafaxine XR on neuropathic pain was similar to that of placebo. However venlafaxine XR resulted in statistically significant and clinically meaningful reductions in nociceptive pain site intensity and interference even after controlling for anxiety, depression, and multiple pain sites within the same individual. For those who achieved a minimally effective dose of venlafaxine XR, some additional evidence of effectiveness was noted for those with mixed (both neuropathic and nociceptive) pain sites. CONCLUSIONS: Venlafaxine XR could complement current medications and procedures for treating pain after SCI and MDD that has nociceptive features. Its usefulness for treating central neuropathic pain is likely to be limited. Research is needed to replicate these findings and determine whether the antinociceptive effect of venlafaxine XR generalizes to persons with SCI pain without MDD.

A randomized controlled trial of venlafaxine XR for major depressive disorder after spinal cord injury: Methods and lessons learned.

CONTEXT/OBJECTIVE: We describe the rationale, design, methods, and lessons learned conducting a treatment trial for major depressive disorder (MDD) or dysthymia in people with spinal cord injury (SCI). DESIGN: A multi-site, double-blind, randomized (1:1) placebo controlled trial of venlafaxine XR for MDD or dysthymia. Subjects were block randomized and stratified by site, lifetime history of substance dependence, and prior history of MDD. SETTING: Six SCI centers throughout the United States. PARTICIPANTS: Across participating centers, 2536 subjects were screened and 133 were enrolled into the trial. Subjects were 18-64 years old and at least 1 month post-SCI. Interventions Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule. OUTCOME MEASURES: The primary outcome was improvement in depression severity at 12 weeks. The secondary outcome was improvement in pain. RESULTS: This article includes study methods, modifications prompted by a formative review process, preliminary data on the study sample and lessons learned. We describe common methodological and operational challenges conducting multi-site trials and how we addressed them. Challenges included study organization and decision making, staff training, obtaining human subjects approval, standardization of measurement and treatment, data and safety monitoring, subject screening and recruitment, unblinding and continuity of care, database management, and data analysis. CONCLUSIONS: The methodological and operational challenges we faced and the lessons we learned may provide useful information for researchers who aim to conduct clinical trials, especially in the area of medical treatment of depression in people with SCI.

Poor interoperability of the Adams-Harbertson method for analysis of anthocyanins: comparison with AOAC pH differential method.

The poor interoperability of anthocyanin glycosides measurements by two pH differential methods is documented. Adams-Harbertson, which was proposed for commercial winemaking, was compared to AOAC Official Method 2005.02 for wine. California bottled wines (Pinot Noir, Merlot, and Cabernet Sauvignon) were assayed in a collaborative study (n=105), which found mean precision of Adams-Harbertson winery versus reference measurements to be 77 +/- 20%. Maximum error is expected to be 48% for Pinot Noir, 42% for Merlot, and 34% for Cabernet Sauvignon from reproducibility RSD. Range of measurements was actually 30 to 91% for Pinot Noir. An interoperability study (n=30) found Adams-Harbertson produces measurements that are nominally 150% of the AOAC pH differential method. Large analytical chemistry differences are: AOAC method uses Beer-Lambert equation and measures absorbance at pH 1.0 and 4.5, proposed a priori by Flueki and Francis; whereas Adams-Harbertson uses "universal" standard curve and measures absorbance ad hoc at pH 1.8 and 4.9 to reduce the effects of so-called co-pigmentation. Errors relative to AOAC are produced by Adams-Harbertson standard curve over Beer-Lambert and pH 1.8 over pH 1.0. The study recommends using AOAC Official Method 2005.02 for analysis of wine anthocyanin glycosides.

An investigation of PreMCI: subtypes and longitudinal outcomes.

BACKGROUND/AIMS: To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI). METHODS: We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination. RESULTS: The rate of progression to MCI or dementia over an average of 2- to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI-Clinical, 38.9% for amnestic PreMCI-NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression. CONCLUSION: Distinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.

The relationship between performances on neuropsychological symptom validity testing and the MCMI-III in patients with fibromyalgia.

Fibromyalgia is a disorder that frequently presents with both cognitive complaints and psychiatric symptoms. This study investigated the association between Symptom Validity Test (SVT) performance and psychiatric symptoms as measured by the Millon Clinical Multiaxial Inventory-III (MCMI-III), a common measure of psychopathology. A total of 72 fibromyalgia patients at a tertiary care clinic completed the MCMI-III, an embedded cognitive symptom validity test (Reliable Digit Span), and a stand-alone cognitive symptom validity test (the Word Memory Test or Test of Memory Malingering). Of these patients, 21% failed a stand-alone SVT, whereas an additional 15% failed both a stand-alone and embedded SVT. Individuals who failed both stand-alone and embedded cognitive SVTs had higher scores on a number of MCMI-III personality subscales and had elevated scores on MCMI-III modifying indices compared to individuals who passed cognitive SVTs. Moreover, SVT performance was significantly correlated with multiple MCMI-III scores, including modifying indices, as well as the somatoform, depression, and anxiety subscales. In sum, cognitive and psychological symptom validity scores were significantly related. Given the new emphasis on cognitive complaints as part of the fibromyalgia diagnostic criteria, neuropsychological evaluation of both cognitive and psychological symptom validity should be a part of a comprehensive diagnostic assessment.

Mental health and outcomes in primary total joint arthroplasty.

A consecutive series of 640 total joint arthroplasty patients was interviewed before surgery and at a minimum of 2 years following surgery. Statistical analyses were conducted to examine the effect of psychological distress and other patient characteristics on outcomes (Western Ontario and McMaster Universities Osteoarthritis Index, Short Form 36, and Quality of Well-Being index). Before and after surgery, distressed subjects had significantly lower scores than nondistressed subjects for most dependent measures (P range, .05 ≤ .001). All mean outcomes improved by follow-up in both groups (P ≤ .001) except mental health scores of nondistressed subjects. Stepwise regression analysis found that low baseline mental health score, non-Hispanic ethnicity, and fewer years since procedure were the strongest predictors of worse Western Ontario and McMaster Universities Osteoarthritis Index scores at follow-up. Although the magnitude of improvement is similar to nondistressed subjects, distressed patients do not achieve comparable functional and psychosocial outcomes.

Assessing the progression of mild cognitive impairment to Alzheimer's disease: current trends and future directions.

With the advent of advances in biomarker detection and neuropsychological measurement, prospects have improved for identifying and tracking the progression of Alzheimer's disease (AD) from its earliest stages through dementia. While new diagnostic techniques have exciting implications for initiating treatment earlier in the disease process, much work remains to be done to optimize the contributions of the expanding range of tools at the disposal of researchers and clinicians. The present paper examines recent work in cerebrospinal fluid biomarkers, magnetic resonance imaging, positron emission tomography, neuropsychological measures, and functional assessment. The strengths and weaknesses of current methodologies are explored and discussed. It is concluded that AD from its mild cognitive impairment state through dementia represents a continuous process, and that progression over time can best be accomplished by interval-level variables. Biomarkers that are most sensitive to early AD may not be the most optimal for monitoring longitudinal change, and it is likely that multivariate models incorporating cognitive measures, functional variables and biomarker data will be the most fruitful avenues for future research.

Is it time for a new practice environment? Part III: designing and constructing your new practice environment.

In school, architects are taught "Form follows function," but all too often this concept is forgotten or not followed in planning medical practice environments. Things such as the architecture (look) of the building, the budget, the view from the office, etc., drive planning decisions when none of those can help promote doctor-patient interaction. The planning of a medical practice environment should follow an operational approach that is focused on the concept that best utilizing the doctors' time to provide care to more people is the ultimate goal. All decisions, from where the building is located, to where the exam rooms are located within the building, to how communication is handled, should all be based on how they best facilitate patent and doctor interaction.

Is it time for a new practice environment? Part II: an operational approach to determining space needs.

In today's practice of medicine, seeing patients requires space. The amount and type of space a practice needs are based on the volume of patients to be seen, services provided, and the number of providers in the practice. To evaluate whether or not your current practice space effectively houses your practice or if a new building could better support your practice, the amount and type of space the practice needs must be determined. Once this space needs assessment is done, it can be used to evaluate the current practice environment, and if need be develop preliminary drawings to evaluate new space. Both operational flow and the economics of creating the new improved practice (whether it is a renovation of existing space or brand new space) should be compared.

Is it time for a new practice environment? An operational look at your practice.

In this era of reimbursement not keeping pace with overhead and healthcare reform an unknown, it is more important than ever to assess the use of the doctors' and mid-level providers' time in your practice. There could be a very large untapped revenue source in the misallocated time of these providers that could help your practice increase patient volume and therefore practice revenue. Accessing this untapped revenue source may require additional resources in space and staff. To determine the level of untapped revenue and the investment that will be required to access that revenue, an objective assessment of your current practice flow is required.

Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice.

OBJECTIVE: To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE(-/-) mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis. METHODS: A total of 43, 12-week-old, apoE(-/-) mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations. RESULTS: There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05). CONCLUSIONS: These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.

Adams-Harbertson protein precipitation-based wine tannin method found invalid.

The poor precision of the Adams-Harbertson wine tannin assay which was proposed for commercial winemaking, thereby creating the real possibility of quality control problems, is documented. The method is a version of the Hagerman and Butler protein precipitation-based tannin method. An extensive invalidation of the assay results with luxury wine data shows that the assay cannot distinguish bottled wine with reasonable accuracy. Five laboratories used Adams-Harbertson to assay 9 replicates each, of 3 bottled wines (n = 135) found in California supermarkets, with tannin concentrations of nominally 500 and 1000 ppm by high-performance liquid chromatography (HPLC). Reliability exceeded the +/-5% industry requirement by nominally 5 times (z-score based on 5% distribution). Coefficient of variation was +/-27%, making the standard deviation range 54% for Pinot Noir, 34% for Merlot, and 44% for Cabernet Sauvignon. Validity exceeded the 100% requirement. Intralaboratory validity recovery was 55-63%. Interwinery validity was 71-178% of the mean for Pinot Noir, 81-144% for Merlot, and 83-164% for Cabernet Sauvignon. Range as a function of the mean was 89% for Pinot Noir, 55% for Merlot, and 67% for Cabernet Sauvignon. Expect intermethod validity to be nominally 50%, i.e., percent recovery to HPLC. These statistically significant errors were predicted by the literature. First-order error is related to the tannin-protein equilibrium constant (Ka), as suggested by the original author, Hagerman, and the protein equivalence point error as suggested by Silber. This does not obviate second-order errors for tannin-protein analytical chemistry. Winemakers using the measurements risk making wines that are relatively more tannic than the measurements report.

Oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion in macrophages and vascular cells.

Oxytocin is synthesized and released in the heart and vasculature, tissues that also express oxytocin receptors. Although it has been established this intrinsic cardiovascular oxytocin system is important in normal homeostatic cardiac and vascular regulation, a role for this system in cardiovascular pathophysiology has not been investigated. The current study examined the influence of oxytocin on mechanisms in atherogenesis, oxidative stress, and inflammation in cultured human vascular cells, THP-1 monocytes, and macrophages. Oxytocin receptor protein and mRNA expression, NADPH-dependent superoxide activity, and interleukin-6 secretion were measured. Results demonstrated oxytocin receptor protein and mRNA in THP-1 monocytes and macrophages. Incubation of cells at physiological levels of oxytocin significantly decreased basal and stimulated NADPH-dependent superoxide activity in vascular cells, monocytes, and macrophages by 24-48%. Oxytocin also attenuated interleukin-6 secretion from stimulated THP-1 macrophages and endothelial cells by 56 and 26%, respectively. These findings suggest that oxytocin attenuates vascular oxidative stress and inflammation, two important pathophysiological processes in atherosclerosis. The fact that oxytocin receptors are found in monocytes and macrophages, and oxytocin decreases both superoxide production and release of a proinflammatory cytokine from these cells, suggests a potentially larger role for oxytocin in the attenuation of disease.

The effect of social environment on markers of vascular oxidative stress and inflammation in the Watanabe heritable hyperlipidemic rabbit.

OBJECTIVE: Previous research demonstrated that social environment can influence progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. This study examined the effect of social environment on markers of oxidative stress and inflammation to clarify the physiological pathways potentially responsible for the influence of social environment on disease. METHODS AND RESULTS: WHHL rabbits were assigned to 1 of 3 social groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily; and an individually-caged group. The stable group engaged in more affiliative social behavior than the unstable group. The unstable group showed more agonistic behavior compared with the stable group and higher C-reactive protein levels than the individually caged group. The individually caged group was behaviorally sedentary, had higher 24-hour urinary catecholamine levels than the other groups, and exhibited higher NAD(P)H-oxidase activity in the aortic arch relative to the stable group. CONCLUSIONS: The results suggest that social environment creates distinct behavioral contexts that can affect markers of inflammation and oxidative stress early in the development of atherosclerosis. Specifically, physical inactivity associated with individual caging affects indices of oxidative stress and inflammation. These pathophysiological markers may help to explain behaviorally related differences in the extent of atherosclerosis observed in prior studies.