Postoperative symptoms of psychosis after deep brain stimulation in patients with Parkinson's disease.

OBJECT: Cases of postoperative psychosis in Parkinson's disease patients receiving deep brain stimulation (DBS) treatment have previously been published. However, the magnitude of symptom incidence and the clinical risk factors are currently unknown. This retrospective study sheds light on these issues by investigating psychosis in a group of 128 Parkinson's disease patients who received DBS implants. METHODS: A retrospective chart review was performed to obtain surgery dates, follow-up clinic visit dates, and associated stimulation parameter settings (contacts in use and the polarity of each along with stimulation voltage, frequency, and pulse width) for each patient. Unified Parkinson's Disease Rating Scale II Thought Disorder scores, used as a clinical assessment tool to evaluate the presence of psychosis at each visit, were also collected. The data were compiled into a database and analyzed. RESULTS: The lifetime incidence of psychosis in this cohort of patients was 28.1%. The data suggest that risk of psychosis remains fairly constant throughout the first 5 years after implantation of a DBS system and that patients older at the time of receiving the first DBS implant are not only more likely to develop psychosis, but also to develop symptoms sooner than their younger counterparts. Further analysis provides evidence that psychosis is largely independent of the clinically used electrode contact and of stimulation parameters prior to psychosis onset. CONCLUSIONS: Although symptoms of psychosis are widely seen in patients with Parkinson's disease in the years following stimulator placement, results of the present suggest that most psychoses occurring postoperatively are likely independent of implantation and stimulation settings.

Baclofen dosage after traumatic spinal cord injury: a multi-decade retrospective analysis.

OBJECTIVES: To perform an analysis of oral baclofen dosage in patients with traumatic spinal cord injuries over time and to ascertain the clinical determinants of long-term baclofen dosage trends. STUDY DESIGN: Retrospective cohort study of patient records from the PM&R units at the Johns Hopkins Bayview Medical Center and the Johns Hopkins Hospital. SUBJECTS: A total of 115 PM&R patients suffering spinal cord injury due to trauma leading to either complete or incomplete paralysis. The modes of injury included were motor vehicle accidents (MVA) (n=39), gunshot wounds (GSW) (n=55), falls (n=17), diving (n=2), workplace (n=1) and swimming (n=1) accidents. The location of injury in the spinal cord was categorized into either cervical (n=52), thoracic (n=59), lumbar (n=2), or unspecified (n=2). RESULTS: From time of injury, an aggregate of all dosage assignments for each patient demonstrated a significant yearly increase in baclofen dosage (1.26 mg/year, p<0.01). Baclofen dosage for MVA cases were seen to rise at 4.99 mg/year (p<0.0001). Kaplan-Meier analysis revealed that GSW patients received their first baclofen dosage earlier than MVA patients (log-rank p<0.05, unadjusted). CONCLUSIONS: We observed a marginal increase in baclofen dosage over nearly 25 years in a single provider's patient database and observed different timings of first dose between two causes of traumatic SCI. These results provide an estimate of baclofen dosage trends over time after spinal cord injury and may be useful for patient counseling or as a method to assess costs of providing SCI patient care.

Pharmacological protection from radiation ± cisplatin-induced oral mucositis.

PURPOSE: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. METHODS AND MATERIALS: Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. RESULTS: Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. CONCLUSIONS: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

Prevention of radiation-induced oral mucositis after adenoviral vector-mediated transfer of the keratinocyte growth factor cDNA to mouse submandibular glands.

PURPOSE: The study aims to evaluate if human keratinocyte growth factor (hKGF), secreted after transduction of murine salivary glands with adenoviral vectors, can prevent oral mucositis resulting from radiation. EXPERIMENTAL DESIGN: Two serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1alpha-hKGF and AdLTR(2)EF1alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis (ulcers on tongue). One day before irradiation, the above viral vectors or an empty vector, Adcontrol, was given (10(10) particles per gland) to both submandibular glands by retrograde ductal instillation. Each experiment included five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1alpha-hKGF, or AdLTR(2)EF1alpha-hKGF). Blood, saliva, submandibular glands, and tongue were collected on day 7 for single-dose studies or day 10 for fractionated dosing. hKGF levels were measured by ELISA. RESULTS: In three separate single-dose irradiation experiments, lingual ulcers were dramatically reduced after either KGF-expressing vector. Similarly, in two separate fractionated irradiation experiments, the hKGF-expressing vectors completely prevented ulcer formation. QPCR data indicated that approximately 10(7) to 10(8) particles of each vector remained in the targeted submandibular glands at the terminal time. Transgenic hKGF protein was found at high levels in saliva, serum, and submandibular gland extracts. CONCLUSIONS: hKGF gene transfer to salivary glands prevented radiation-induced oral mucositis in mice. This proof of concept study suggests that transgenic hKGF secreted from transduced salivary glands may be useful clinically to prevent oral mucositis caused by radiation.

Comparative sensitivity of stopwatch methodology and conventional pain assessment measures for detecting early response to triptans in migraine: results of a randomized, open-label pilot study.

BACKGROUND: The standard measure of efficacy used in migraine trials is a 4-point patient-rated headache pain intensity (HPI) scale. However, it has been suggested that using a stopwatch to measure the time to meaningful pain relief can provide a more precise measurement of treatment response. OBJECTIVE: This study evaluated the sensitivity of a stopwatch method for detecting meaningful relief of headache pain and the correlation of this method with the HPI scale and a 5-point pain relief scale. METHODS: In this open-label, parallel-group pilot study, patients were randomized to receive oral eletriptan 40 mg, eletriptan 80 mg, or rizatriptan 10 mg for the treatment of a single acute migraine attack. The effect of study treatment on migraine pain was assessed immediately before dosing and at 0.5, 1, 1.5, 2, 3, and 4 hours after dosing. At each time point, patients recorded the 3 types of pain assessment in a patient diary. HPI was rated using the standard 4-point International Headache Society pain intensity scale (from 0 = no pain to 3 = severe pain). Pain relief was rated on a 5-point pain relief scale (from 4 = no relief to 0 = complete relief). The time to the onset of meaningful pain relief was measured using a stopwatch. At 4 hours after dosing, patients provided a global rating of the overall efficacy of study medication on a 5-point scale (from 0 = poor to 4 = excellent). RESULTS: Seventy-nine patients participated in the trial (78.5% female; mean [SD] age, 37.7 [9.8] years; 58.2% white). The median times to meaningful pain relief measured by stopwatch were 84, 72, and 93 minutes for eletriptan 40 mg, eletriptan 80 mg, and rizatriptan 10 mg, respectively (log-rank P = 0.029, eletriptan 80 mg vs rizatriptan 10 mg). At 90 minutes (approximating the median time to meaningful pain relief on the stopwatch), headache response rates using HPI scoring (mild to no pain) were 65%, 68%, and 52% in the respective treatment groups, with no significant difference between groups. On the pain relief scale, the corresponding mean (SD) scores at 90 minutes were 1.6 (1.2), 1.4 (1.3), and 2.0 (1.4) (P = NS). The pain relief-defined response (> or = 75% pain relief) at 90 minutes did not differ significantly between the 3 treatment groups (62%, 56%, and 48%). Detection of early improvement (0.5 and 1 hour) was similar with the HPI and pain relief scales. CONCLUSION: The results of this open-label pilot study suggest the convergent validity of 3 pain-assessment methods in migraine, but indicate that the use of a stopwatch may be a more sensitive method for detecting between-group differences.

Sumatriptan and naproxen sodium for the acute treatment of migraine.

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. BACKGROUND: The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study. RESULTS: In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. CONCLUSIONS: This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.

American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies.

The aim of this study was to evaluate the utility of the American Pain Society (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to determine the onset of action of celecoxib in the treatment of acute flare pain in patients with OA of the knee or hip. Pooled data from three pivotal, randomized, double-blind, placebo-controlled, 12-week trials of patients with OA who exhibited a flare of disease activity after withdrawal of nonsteroidal anti-inflammatory drug or analgesic therapy were evaluated. Patients completed the APS Pain Measure Questionnaire, which evaluates pain intensity and quality of life, at baseline and daily for the first 7 days of therapy. In addition, patients underwent a range of standard OA assessments to evaluate the analgesic efficacy of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010 received celecoxib, 513 received naproxen, and 518 received placebo). Within the first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the amount of acute pain experienced compared with placebo for four of the five measures, and statistical significance for the remaining parameter, "pain in the last 24 hours," was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief observed with celecoxib was maintained for the APS evaluation period. Long-term efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be continuous and maintained for at least the 12 weeks of the study and that it was equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study demonstrates that the APS questionnaire is a useful measure of pain and therapeutic response in OA. Celecoxib furthermore seems to be an effective acute and chronic analgesic in OA.