Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

OBJECTIVE: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. METHODS: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. RESULTS: PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. CONCLUSIONS: Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.

Changes in the frequencies of human hematopoietic stem and progenitor cells with age and site.

This study enumerated CD45(hi)/CD34(+) and CD45(hi)/CD133(+) human hematopoietic stem cells (HSCs) and progenitor granulocyte-macrophage colony forming cells (GM-CFCs) in blood and trochanteric and femoral bone marrow in 233 individuals. Stem cell frequencies were determined with multiparameter flow cytometry and using an internal control to determine the intrinsic variance of the assays. Progenitor cell frequency was determined using a standard colony assay technique. The frequency of outliers from undetermined methodological causes was highest for blood, but less than 5% for all values. The frequency of CD45(hi)/CD133(+) cells correlated highly with the frequency of CD45(hi)/CD34(+) cells in trochanteric and femoral bone marrow. The frequency of these HSC populations in trochanteric and femoral bone marrow rose significantly with age. In contrast, there was no significant trend of either of these cell populations with age in the blood. Trochanteric marrow progenitor GM-CFCs showed no significant trends with age, but femoral marrow GM-CFCs trended downward with age, potentially because of the reported conversion of red marrow at this site to fat with age. Hematopoietic stem and progenitor cells exhibited changes in frequencies with age that differed between blood and bone marrow. We previously reported that side population (SP) multipotential HSC, which includes the precursors of CD45(hi)/CD133(+) and CD45(hi)/CD34(+), decline with age. Potentially the increases in stem cell frequencies in the intermediate compartment between SP and GM progenitor cells observed in this study represent a compensatory increase for the loss of more potent members of the HSC hierarchy.

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging.

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells.

Testing an alternate informed consent process.

BACKGROUND: One of the main problems in conducting clinical trials is low participation rate due to potential participants' misunderstanding of the rationale for the clinical trial or perceptions of loss of control over treatment decisions. OBJECTIVES: The objective of this study was to test an alternate informed consent process in cardiac rehabilitation participants that involved the use of a multimedia flip chart to describe a future randomized clinical trial and then asked, hypothetically, if they would participate in the future trial. METHODS: An attractive and inviting visual presentation of the study was created in the form of a 23-page flip chart that included 24 color photographs displaying information about the purpose of the study, similarities and differences between the two treatment groups, and the data collection process. We tested the flip chart in 35 cardiac rehabilitation participants. Participants were asked if they would participate in this future study on two occasions: immediately after the description of the flip chart and 24 hours later, after reading through the informed consent document. Participants were also asked their perceptions of the flip chart and consent process. RESULTS: Of the 35 participants surveyed, 19 (54%) indicated that they would participate in the future study. No participant changed his or her decision 24 hours later after reading the full consent form. The participation rate improved 145% over that of an earlier feasibility study where the recruitment rate was 22%. Most participants stated that the flip chart was helpful and informative and that the photographs were effective in communicating the purpose of the study. DISCUSSION: Participation rates could be enhanced in future clinical trials by using a visual presentation to explain and describe the study as part of the informed consent process. More research is needed to test alternate methods of obtaining informed consent.

Stress infrared telethermography is useful in the diagnosis of complex regional pain syndrome, Type I (formerly reflex sympathetic dystrophy).

The objective of this paper is to assess the sensitivity, specificity, and predictive value (PV) of stress infrared telethermography (IRT) in the Complex Regional Pain Syndrome, Type I (CRPS-I). One hundred eighty-five consecutive patients (47 men, 138 women) with 205 pairs of chronically painful limbs (upper, lower, or both) were examined by pain specialists in neurology, physiatry, and anesthesia, who then reached a consensus diagnosis. A clinical diagnosis of CRPS-I required at least two of the following observations: burning pain, vasomotor changes, diaphoresis, trophic changes, allodynia. Patients with only one criterion were classified as possible CRPS-I; those with none were judged not to have CRPS-I. Patients and 24 asymptomatic control subjects underwent stress IRT, which was considered positive for CRPS-I if it showed three of the following: quantitative thermal emission of >1.00 degrees C, abnormal distal thermal gradient patterns, presence of a "thermal marker", and abnormal response to functional cold water autonomic stress testing. By clinical criteria, CRPS-I was diagnosed in 73 pairs of limbs; not CRPS-I was diagnosed in 70; and 62 pairs had possible CRPS-I. Excluding possible CRPS-I cases, there were 5 false-negative stress IRTs (sensitivity 93%) and 7 false-positive results (specificity 89%). Based on estimated 50% prior probability for our population, the positive PV is 90% and the negative PV 94%. None of the control subjects exhibited thermographic evidence of CRPS. It is concluded that the stress IRT is a sensitive and specific indicator of CRPS-I.

Exertional, Cough, and Sexual Headaches.

The International Headache Society applies the term exertional headache to head pain precipitated by exertion. The Society recognizes cough headache and sexual headache as distinct diagnoses. All three types of headache share characteristics and mechanisms, and together may be considered as headache provoked by exertional factors ( Table 1). In distinction to more typical headaches, such as tension-type headaches or migraine, HAPEF is brief, lasting seconds to minutes, and begins immediately following the precipitating exertion. Headache provoked by exertional factors may occur by itself, or in association with headaches that are not exertional. Secondary (or symptomatic) HAPEF arises as a result of an underlying disorder; primary (or benign) HAPEF has no underlying cause. Clinicians must consider HAPEF potentially serious until appropriate investigations are undertaken. Fortunately, disorders that underlie secondary headaches usually become apparent with examination or laboratory testing. Clinical features of the headaches may also offer a clue (Table 2). Several theories have been put forth to explain the underlying mechanism of exertional, cough, and sexual headache. The leading explanation regarding all three involves exertional factors leading to a sudden increase in intracranial pressure or an inappropriate reaction in the cerebral vasculature. Because exertion may also be a migraine trigger, neural hypersensitivity, similar to migraine, may also play a role in HAPEF. The literature contains only several small case studies that deal with treatment of exertional headache, and just one double blind, placebo-controlled study. The consensus to date is that secondary HAPEF resolves if the underlying illness can be treated; primary HAPEF responds well to prophylactic treatment. Treatment strategy varies little among headaches precipitated by cough, sex, or other forms of exertion. Avoidance strategies, sometimes combined with medication (particularly indomethacin), can effectively treat headaches produced by exertional factors in most cases.

Post-traumatic Headache.

Headache is the most common symptom after closed head injury, persisting for more than 2 months in 60% of patients. Rarely does headache occur in isolation. Cervical pain is a frequent accompaniment. Post-traumatic headache is often one of several symptoms of the postconcussive syndrome, and therefore may be accompanied by additional cognitive, behavioral, and somatic problems. Acute post-traumatic headaches may begin at the time of injury and continue for up to 2 months post-injury. Although onset proximate to the time of injury is most common, any new headache type occurring within this period of time is referred to as an acute post-traumatic headache. If such headaches persist beyond the first two months post-injury, they are subsequently referred to as chronic post-traumatic headaches. Over time, post-traumatic headaches may take on a pattern of daily occurrence. If aggressive treatment is initiated early, posttraumatic headache is less likely to become a permanent problem. Once "windup" of post-traumatic headaches occurs, the cycle of ongoing headaches is more difficult to interrupt. The mechanism of post-traumatic headache is poorly understood. Trauma-induced headaches are usually heterogeneous in nature, often including both tension-type pain and intermittent migraine-like attacks. Rebound-headaches may develop from overuse of analgesic medications, and the occurrence of such may complicate significantly the diagnosis of post-traumatic headache. Adequate treatment typically requires both "peripheral" and "central" measures. Understanding the general principles of treatment, especially appropriate use of preventive and abortive medications, will most usefully guide treatment. There is scant literature with which to direct treatment selection for post-traumatic headache. Consequently, treatments for post-traumatic headache are based on those prescribed for phenomenologically similar but etiologically distinct headache disorders. Delayed recovery from post-traumatic headache may be a result of inadequately aggressive or ineffective treatment, overuse of analgesic medications resulting in analgesia rebound phenomena, or comorbid psychiatric disorders (eg, post-traumatic stress disorder, insomnia, substance abuse, depression, or anxiety).