Long-term treatment with methylphenidate for fatigue after traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) may cause long-lasting post-concussive symptoms, such as mental fatigue and concentration difficulties, and this may become the main hindrance for returning to work and studies. There is currently no effective treatment for long-lasting mental fatigue. In this hypothesis generating study, the long-term effects of methylphenidate on mental fatigue, cognitive function, and safety were assessed. MATERIALS & METHODS: Thirty participants who suffered from long-term post-concussion symptoms after a mild TBI or moderate TBI and who had reported positive effects with methylphenidate during an initial phase of this follow-up study were treated with methylphenidate for a further six months. RESULTS: After six-month follow-up, effects on Mental Fatigue Scale (MFS), depression, anxiety, and cognitive function (processing speed, attention, working memory) were significantly improved compared to baseline data (P < 0.001, respectively). Heart rate was significantly increased (P = 0.01), while blood pressure was not changed. CONCLUSIONS: Individuals suffering from prolonged symptoms after TBI reported reduced mental fatigue and improved cognitive functions with long-term methylphenidate treatment. It is suggested that methylphenidate can be a treatment option for long-term mental fatigue and cognitive impairment after a TBI, but further randomized control research is warranted.

Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury.

OBJECTIVE: Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury. METHODS: Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments. RESULTS: Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate. CONCLUSIONS: Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.

Evaluation of dosage, safety and effects of methylphenidate on post-traumatic brain injury symptoms with a focus on mental fatigue and pain.

OBJECTIVE: The neurobehavioural symptoms and pain following traumatic brain injury (TBI) can be long-lasting. The condition impairs the persons' ability to function in their work, studies and gatherings with family and friends. The aim of this study was to investigate dosage, safety and effects of methylphenidate on mental fatigue and pain. METHODS: Twenty-nine physically-well rehabilitated TBI victims, 28 with a mild TBI and one with TBI and also with pain in the neck, shoulders and head were included in the study. Methylphenidate was tested in each patient using three treatment strategies: no medication, low dose (5 mg × 3) and normal dose (20 mg × 3) for 4 weeks using a randomized cross-over design. RESULTS: Twenty-four patients completed the three treatment periods. Five participants discontinued, four females due to adverse reactions and one male due to attenuated motivation. Only minor adverse events were reported. Methylphenidate significantly decreased mental fatigue, as evaluated by the Mental Fatigue Scale (p < 0.001), and the effects on mental fatigue were dose-dependent. No effect on pain was detected. CONCLUSIONS: Methylphenidate decreased mental fatigue for subjects suffering a traumatic brain injury, the treatment is considered to be safe and is recommended, starting with a low dose.

Pharmaceutical treatment patterns for patients with a diagnosis related to chronic pain initiating a slow-release strong opioid treatment in Sweden.

Slow-release strong opioids (SRSO) are indicated in patients with severe chronic pain. Side effects, lack of efficacy and risk of dependency limit their use in clinical practice. The aim of this study was to explore prescription patterns of SRSO in Swedish real-world data on patients with a diagnosis related to chronic pain (DRCP). Patient-level data were extracted from the national prescriptions register and a regional register with diagnosis codes. The prescription sequences, switches, co-medications, and strengths over time were analyzed for cancer and noncancer patients. Of 840,000 patients with a DRCP, 16,257 initiated treatment with an SRSO in 2007 to 2008. They were 71 years old on average; 60% were female and 34% had cancer. The most common first prescription was oxycodone (54%) followed by fentanyl (19%), buprenorphine (14%), and morphine (13%). 63% refilled their prescription within 6 months, and 12% switched to another SRSO, most commonly fentanyl. After 3 years, 51% of cancer and 27% of noncancer patients still being in contact with health care remained on any SRSO. Of noncancer patients, 35% had a psychiatric co-medication (SSRI or benzodiazepine). In conclusion, fewer patients remain on SRSO in the long-term in clinical practice than reported in previous clinical trials. Oxycodone is the most common first SRSO prescription and one-third of patients get a prescription indicating psychiatric comorbidity. Our interpretation of these findings are that there is need for better treatment options for these patients, and that more effort is needed to improve treatment guidelines and to ascertain that these guidelines are followed.

Socio-economic burden of patients with a diagnosis related to chronic pain--register data of 840,000 Swedish patients.

BACKGROUND: Chronic pain constitutes a substantial socio-economic challenge but little is known about its actual cost. AIM: To estimate the direct and indirect costs of patients with a diagnosis related to chronic pain (DRCP), to determine variation in these costs across different diagnosis groups, and to identify what resources constitute the most important components of costs. METHODS: Patient level data from three administrative registries in Västra Götalandsregionen in Sweden including inpatient and outpatient care, prescriptions, long-term sick-leaves, and early retirement were extracted. Patients with a DRCP between January 2004 and November 2009 were selected. RESULTS: In total, 840,000 patients with a DRCP were identified. The mean total costs per patient and year were estimated at 6400 EUR but were higher for patients with cancer (10,400 EUR). Patients on analgesic drugs had more than twice as high costs as patients without analgesic drugs, on average. Indirect costs (sick-leaves and early retirement) constituted the largest cost component (59%) followed by outpatient (21%) and inpatient care (14%), whereas analgesic drug prescriptions constituted less than 1 percent of the total. CONCLUSIONS: The socio-economic burden of patients with a diagnosis related to chronic pain amounts to 32 billion EUR per year, when findings from Västra Götalandsregionen are extrapolated to the whole of Sweden. This compares to a fifth of the total Swedish tax burden in 2007 or about a tenth of Swedish GDP. This study does not provide evidence on what costs are caused by chronic pain per se. However, the higher costs of patients on analgesic drugs might indicate that the consequences of pain are of major importance.

Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris--results from the European Angina Registry Link Study (EARL).

OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris defined as severe angina due to coronary artery disease resistant to conventional pharmacological therapy and/or revascularisation. METHODS: During 2003-2005, all patients with refractory angina referred for SCS treatment at 10 European centres were consecutively included in the European registry for refractory angina (European Angina Registry Link, EARL), a prospective, 3-year follow-up study. In the present study, the SCS-treated patients were followed-up regarding angina symptoms and quality of life assessed was with a generic (Short Form 36, SF-36) and a disease-specific (Seattle Angina Questionnaire, SAQ) quality of life questionnaire. RESULTS: In total, 235 patients were included in the study. After screening, 121 patients were implanted and followed up 12.1 months after implantation. The implanted patients reported fewer angina attacks (p<0.0001), reduced short-acting nitrate consumption (p<0.0001) and improved Canadian Cardiovascular Society class (p<0.0001). Furthermore, quality of life was significantly improved in all dimensions of the SF-36 and the SAQ. Seven (5.8%) of the implanted patients died within 1 year of follow up. CONCLUSIONS: SCS treatment is associated with symptom relief and improved quality of life in patients with refractory angina pectoris suffering from severe coronary artery disease.

High-frequency, high-intensity transcutaneous electrical nerve stimulation as treatment of pain after surgical abortion.

The aim of the study was to compare the pain-relieving effect and the time spent in the recovery ward after treatment with high-frequency, high-intensity transcutaneous electrical nerve stimulation (TENS) or intravenous (IV) conventional pharmacological treatment after surgical abortion. Two-hundred women who underwent surgical abortion and postoperatively reported a visual analogue scale (VAS) pain score3 were included. The patients were randomised to TENS or conventional pharmacological treatment for their postoperative pain. The TENS treatment was given with a stimulus intensity between 20 and 60 mA during 1 min and repeated once if insufficient pain relief (VAS3). In the conventional pharmacological treatment group, a maximum dose of 100 microg fentanyl was given IV. There was no difference between the groups with regard to pain relief according to the VAS pain score (TENS=VAS 1.3 vs. IV opioids=VAS 1.6; p=0.09) upon discharge from the recovery ward. However, the patients in the TENS group spent shorter time (44 min) in the recovery ward than the conventional pharmacological treatment group (62 min; p<0.0001). The number of patients who needed additional analgesics in the recovery ward was comparable in both groups, as was the reported VAS pain score upon leaving the hospital (TENS=2.0 vs. conventional pharmacological treatment=1.8, NS). These results suggest that the pain-relieving effect of TENS seems to be comparable to conventional pharmacological treatment with IV opioids. Hence, TENS may be a suitable alternative to conventional pain management with IV opioids after surgical abortion.

Nutcracker oesophagus: a double-blind, placebo-controlled, cross-over study of the effects of lansoprazole.

BACKGROUND: Nutcracker oesophagus is characterized by high-amplitude oesophageal contractions. Recent data have shown a high prevalence of gastro-oesophageal acid reflux in patients with nutcracker oesophagus and, in open-label trials, patients seemed to benefit from acid suppression. Therefore, it has been suggested that non-cardiac chest pain in patients with nutcracker oesophagus may be related to reflux rather than to the motor abnormality itself. AIMS: To investigate the effect of intensive acid-suppressive treatment on chest pain in patients with nutcracker oesophagus. METHODS: Nineteen patients with nutcracker oesophagus received lansoprazole or placebo in a double-blind, randomized, cross-over study. RESULTS: Significant reductions in pain intensity (P < 0.006) and pain duration (P < 0.05) were registered during the study. The magnitude of symptom relief achieved with lansoprazole did not differ significantly from that achieved with placebo. The motility pattern did not change during the study. CONCLUSIONS: This study does not prove that acid-suppressive therapy is effective for pain relief in nutcracker oesophagus. As the amelioration of pain was not accompanied by any change in the nutcracker oesophagus pattern, it is unlikely that the high-amplitude oesophageal contractions are the cause of pain. Thus, the possible role of acid in the pathophysiology of pain in nutcracker oesophagus needs further study.

Cost-effectiveness of spinal cord stimulation versus coronary artery bypass grafting in patients with severe angina pectoris--long-term results from the ESBY study.

The present study is a 2-year follow-up of the 104 patients participating in the ESBY study (Electrical Stimulation versus Coronary Artery Bypass Surgery in Severe Angina Pectoris), a randomised prospective study including patients with increased surgical risk and no prognostic benefit from revascularisation. Hospital care costs, morbidity and causes of death after spinal cord stimulation (SCS) and coronary artery bypass grafting (CABG) were assessed, as well as the complication rate of SCS treatment. SCS proved to be a less expensive symptomatic treatment modality of angina pectoris than CABG (p < 0.01). The SCS group had fewer hospitalisation days related to the primary intervention (p < 0.0001) and fewer hospitalisation days due to cardiac events (p < 0.05). The groups did not differ with regard to causes of death. There were no serious complications related to the SCS treatment.

Long-term effects of spinal cord stimulation and coronary artery bypass grafting on quality of life and survival in the ESBY study.

AIMS: To assess the long-term outcome regarding quality of life and survival in patients who were included in the ESBY study 1992-1995. The ESBY study (Electrical Stimulation versus Coronary Artery Bypass Surgery in Severe Angina Pectoris) included 104 patients-with severe angina, increased surgical risk and no prognostic benefits from revascularization-randomized to coronary artery bypass grafting or spinal cord stimulation. METHODS AND RESULTS: The ESBY patients' quality of life was analysed using two questionnaires, and 5-year mortality was assessed. Quality of life improved significantly 6 months after spinal cord stimulation and coronary artery bypass grafting, respectively, compared to run-in (P<0.001). The results were consistent after 4.8 years. The 5-year mortality was 27.9%. There were no significant differences between the groups. CONCLUSIONS: Spinal cord stimulation as well as coronary artery bypass grafting offered long-lasting improvement in quality of life. Survival up to 5 years was comparable between the groups. Both methods can be considered as effective treatment options for patients with severe angina, increased surgical risks and estimated to have no prognostic benefits from coronary artery bypass grafting.

Diagnosis of nutcracker esophagus, segmental or diffuse hypertensive patterns, and clinical characteristics.

Different criteria have been used for the diagnosis of nutcracker esophagus, but the clinical importance of this is largely unknown. To this end, 45 patients with hypertensive esophageal peristalsis were identified from 572 esophageal investigations, and thereafter explored with regard to diagnostic criteria and clinical background data. The numbers of patients classified as having nutcracker esophagus with different criteria were 25 (by Richter criteria), 39 (by Achem criteria), and 45 (by Gothenburg criteria). In comparison with patients with segmental hypertensive peristalsis, patients with diffuse hypertensive peristalsis were more often referred for chest pain (P < 0.05), less often for reflux symptoms (P < 0.05), and tended to have arterial hypertension less often (P < 0.08). In conclusion, the choice of criteria for the diagnosis of nutcracker hypertensive peristalsis has prominent effects on the number of patients receiving this diagnosis. Moreover, a diffuse nutcracker peristaltic pattern appears more strongly linked to chest pain.

Gastroesophageal acid reflux in patients with nutcracker esophagus.

BACKGROUND: Hypertensive esophageal contraction, called nutcracker esophagus (NE), is the most common motility abnormality associated with cardiac-like chest pain. However, its significance for the development of symptoms has been a matter of controversy for decades, and recently it has been suggested that NE might represent a primarily acid-related esophageal disorder. The frequency of acid-related esophageal dysfunction is studied in an unselected group of patients with NE. METHODS: During the period March 1993 to June 1998, 572 consecutive patients underwent esophageal manometry and 24-h pH monitoring. RESULTS: A motility pattern consistent with NE was found in 45 subjects referred because of chest pain (n = 35), reflux dyspepsia only (n = 8) or epigastric pain (n = 2). Acid-related esophageal dysfunction was noted in 30 (70%) of the NE patients; abnormal acid exposure time (n = 21), esophagitis (n = 2) or positive symptom index (n = 7). In addition, an increased number of reflux episodes were found in another three subjects. NE was more prevalent in subjects referred for chest pain than in those referred for other symptoms (14.3% versus 4.5%; P < 0.0001) and, conversely, 78% of the patients with NE were referred because of chest pain. CONCLUSIONS: Various aspects of acid-related esophageal dysfunction occur frequently in patients with NE, suggesting that acid may play a role in the development of symptoms in NE. Nonetheless, given its association with chest pain, NE could be a marker of a subgroup of patients with acid reflux, distinct from other reflux patients.

[Relief of pain by exercise! Increased physical activity can be a part of the therapeutic program in both acute and chronic pain]. / Mindre ont med motion! Okad fysisk aktivitet kan vara en del av behandlingsprogrammet vid såväl akut som kronisk smärta.

Physical activity can relieve acute as well as chronic pain and has therefore an important role in the treatment of pain, directly or indirectly (by reducing anxiety and lifting depression). Physical inactivity is associated with higher morbidity/mortality and is as detrimental to people with chronic pain as it is to others. When including physical activity in pain treatment programmes it is important to tailor the exercise to suit the individual patient.

[Treatment guidelines for refractory angina pectoris now available. Therapeutic methods varying between behavior therapy and heart transplantation]. / Nu finns riktlinjer för behandling av refraktär angina pectoris. Terapimetoderna har varierat från beteendeterapi till hjärttransplantation.

Refractory angina pectoris is defined as severe angina despite optimal medical and surgical/invasive treatment (CABG, PTCA). The epidemiology of this condition is unknown. The estimated yearly incidence is 2,000 patients in Sweden and 30,000-50,000 patients in Europe. The patient group is growing as a result of improved therapy. A number of additional treatment modalities have been developed during the last decades. The article summarises the scientifically and clinical basis of these treatments and gives recommendations concerning their use.

The effect of transcutaneous electric nerve stimulation in patients with therapy-resistant hypertension.

OBJECTIVES: Afferent nerve stimulation, such as acupuncture and transcutaneous electric nerve stimulation (TENS), has shown a blood pressure reduction in both animal and man. In the present open and non-controlled study we investigated the effect on 24-h ambulatory blood pressure of low frequency TENS in a group of hypertensive subjects who do not respond properly to pharmacological treatment. METHOD: Twelve patients were investigated. The patients were treated with TENS at two acupoints on both forearms for 30 min twice daily during 4 weeks. 24-hour ambulatory blood pressure monitoring was recorded 1 week before, at start, at the end and finally 1 week after the TENS treatment. RESULTS: The blood pressure did not change significantly during the run-in period. After 4 weeks of TENS, the mean systolic blood pressure decreased by 6.3 mm Hg (P < 0.05) and the mean diastolic blood pressure decreased by 3.7 mm Hg (P < 0.05). The blood pressure reduction remained unchanged 1 week after treatment. There was no change in mean heart rate. CONCLUSION: The present study suggests that continuous TENS may have additional blood pressure-lowering properties in hypertensive patients who do not respond properly to pharmacological treatment. The effect of TENS may also have a prolonged effect. Journal of Human Hypertension (2000) 14, 795-798

Effects of spinal cord stimulation and coronary artery bypass grafting on myocardial ischemia and heart rate variability: further results from the ESBY study.

In the present study, 24-hour ECG recordings were analyzed from the Electrical Stimulation versus Coronary Artery Bypass Surgery (ESBY) Study where spinal cord stimulation was compared to CABG (coronary artery bypass grafting) in selected patients with severe angina pectoris. During the monitoring period, the spinal cord stimulation was discontinued to evaluate possible long-term effects of this treatment. The number of ischemic episodes and the duration of ischemia decreased in the CABG group at the follow-up when compared to spinal cord stimulation (p<0.05). In spite of this, the number of anginal attacks decreased (p<0.0001) in both groups. The fact that the anginal symptoms decreased in the spinal cord stimulation group in spite of discontinued stimulation and lack of effects on ischemic ST changes could indicate a long-term primary analgesic effect of this treatment in addition to the well-documented acute anti-ischemic effect.

Acute ischemic chest pain is not associated with increased calcitonin gene-related peptide (CGRP) levels in peripheral plasma nor in the coronary circulation.

Calcitonin gene-related peptide (CGRP) and substance P co-exist in capsaicin-sensitive primary sensory neurons and are released from the myocardium after activation of sensory nerve fibres as well as by ischemia in animals. This study was undertaken to try to clarify the potential involvement of immunoreactive (ir) CGRP in anginal pain and myocardial ischemia in humans. One clinical group (n = 87) and one experimental group (n = 14) were studied. The clinical group was admitted to a coronary care unit with suspected or definite acute myocardial infarction (AMI). The experimental group consisted of patients with severe angina pectoris (NYHA III-IV). This group was subjected to atrial pacing up to the appearance of angina pectoris. Mean irCGRP levels at admission for the clinical group with and without AMI showed no significant difference. Neither were any significant differences found in irCGRP concentrations between patients with pain as compared to those without pain or in the group who had had chest pain >30 min before hospital admission as compared to those with chest pain <30 min. Extraction ratios for lactate and irCGRP was calculated in the experimental group. No statistically significant covariance was found between irCGRP extraction ratio and lactate extraction ratio (r(xy) = -0.006) at the time of appearance of angina during atrial pacing. Despite the facts that CGRP may be liberated by a variety of physiological stimuli and may act as a potent vasodilator in the human vasculature, no evidence has been found in this study that CGRP release is increased as a consequence of ischemia or ischemic pain.