[Structure of pain management facilities in Germany : Classification of medical and psychological pain treatment services-Consensus of the Joint Commission of the Professional Societies and Organizations for Quality in Pain Medicine]. / Struktur der schmerzmedizinischen Versorgung in Deutschland : Klassifikation schmerzmedizinischer Einrichtungen - Konsens der Gemeinsamen Kommission der Fachgesellschaften und Verbände für Qualität in der Schmerzmedizin.

On behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.

[Long-term treatment of chronic pain with low-dose 7-day buprenorphine transdermal patch. Observational data from elderly patients of pain relief and quality of life]. / Langzeitbehandlung chronischer Schmerzen mit niedrig dosiertem 7-Tagetransdermalem-Buprenorphinpflaster. Beobachtungsdaten bei älteren Patienten zu Schmerzintensität und Lebensqualität.

BACKGROUND: Six-months analysis of non-interventionally collected observation data of effectiveness of long-term treatment with low-dose 7-day buprenorphine transdermal patch in elderly patients with chronic pain. METHODS: Analysis of data regarding pain intensity, pain-related impairments of daily life and quality of life documented by 321 pain patients in German primary care (age 72.4 +/- 13.8 years; 67.3% female; musculoskeletal pain 85.4%; mean pain intensity 6.1 +/- 1.2, for 90% > or = 5 NRS11) using standardised self-report instruments (German Pain Questionnaire/German Pain Diary). RESULTS: After initiation with 5/10 microg/h buprenorphine (89.7%/10.3%), treatment was maintained in 57.1/39.1/3.8% patients with stable doses of 5/10/20 microg/h after 6 months. The average pain intensity decreased by 5.1 +/- 1.0 (absolute) to 1.0 +/- 1.0 NRS11 (83.5%), pain-related impairments and burden of pain were reduced by 86.0% and 87.9%, respectively, and pain-related quality of life improved by 97.3% to nearly normalvalues. CONCLUSIONS: Pain treatment of elderly persons with 7-day low-dose transdermal buprenorphine patch on a stable dose regimen resulted in fast, effective and sustained pain relief accompanied by marked improvements in daily life participation and quality of life.

[2-week efficacy and tolerability of flupirtine MR and diclofenac in patients with acute low/back pain--results of a post-hoc subgroup analysis of patient-level data from four non-interventional studies]. / 2-Wochen-Wirksamkeit und -Verträglichkeit von Flupirtin MR und Diclofenac bei akuten Kreuz-/Rückenschmerzen. Ergebnisse einer Post-hoc-Subgruppenanalyse individueller Patientendaten von vier nichtinterventionellen Studien.

BACKGROUND: Current restrictions in use of flupirtine-containing medicines for a maximum of 14 days endorsed by the European Medicines Agency were followed by uncertainty/ambiguity of its analgesic efficacy for the treatment of acute low/back pain. METHODS: Post-hoc selection of patient-level data from non-interventional studies with flupirtine MR and diclofenac with respect to patient age (> or = 18 years), duration of treatment (14 +/- 2 days), indication (acute/subacute low/back pain) and first-line use. Primary endpoint: average 24-hr. pain intensity; secondary endpoints: pain-related disabilities in daily life, 30/50/70% response with respect to pain and pain-related restrictions, frequency of untoward side effects/treatment emergent adverse events. RESULTS: 318/31 patients treated with flupirtine MR/diclofenac fulfilled the inclusion criteria for this subgroup analysis. Starting from comparable demographic and baseline characteristics both treatments were followed by significant effects (p < 0.001). Subgroup comparisons revealed superior effects for flupirtine MR vs. diclofenac for pain relief (p = 0.001), improvement of pain-related restrictions in daily life (p = 0.023), and gastrointestinal/overall tolerability (p < 0.001). CONCLUSIONS: Even for short-term use in patients suffering from muscle-related acute low/back pain, flupirtine MR is superior effective and tolerated compared with the nsaid diclofenac.

[Analgesic and muscle tonus normalizing effect of flupirtine retard in chronic back pain. Results of a standardized therapeutic evaluation applying objective methods for measuring pain pressure threshold, pain pressure tolerance and muscle tension]. / Analgetische und muskeltonus- normalisierende Wirkungvon Flupirtin retard bei chronischen Rückenschmerzen. Ergebnisse einer standardisierten Therapieevaluation unter Verwendung objektiver Verfahren zur Messungvon Druckschmerzschwelle, Druckschmerztoleranz und Muskelspannung.

BACKGROUND: Chronic back pain is mainly caused by painful tension in the back muscles. Thus, analgesics with muscle tone decreasing effects that apparently normalize increased muscle tonus through specific modes of action without disturbing normal muscular movement are an important therapeutic option. Flupirtine retard (Katadolon S long) has provided such an option since 2006. OBJECTIVES: To impartially evaluate the muscle tonus normalizing effects of flupirtine retard by applying specific, objective test methods in patients with chronic musculoskeletal pain under routine practice conditions. METHODS: Prospective standardized evaluation of a treatment with flupirtine retard in 30 patients with continuous chronic, therapy refractory back pain. Measurement of general pain intensity, pain pressure threshold and pain pressure tolerance for trigger-point related pain and muscle tension in the affected back muscles before and during flupirtine retard treatment were performed in a standardized manner. RESULTS: In comparison to the reproducible, constant initial values, the two-week treatment with flupirtine retard led to a significant improvement in all measured muscle-specific indicators: pain pressure threshold (+48%), pain pressure tolerance (+27%) and depth of penetration in the muscle (+18%) (all values p < 0.001). These were also correlated with a clinically observable and statistically significant pain relief from an initial level of 7.0 +/- 1.3 to 3.0 +/- 1.4. CONCLUSION: Flupirtine retard was shown to be a useful, effective and very tolerable therapeutic option for patients with chronic back pain. The improvement of muscle disturbances which are responsible for the pain in addition to pain relief was shown firstly by objective measure methods.

Comparative Efficacy of the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine and Lederle whole-cell component DTP vaccine in German children after household exposure. Pertussis Vaccine Study Group.

BACKGROUND: A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany. DESIGN: Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY). An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age. Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period. RESULTS: During a 3.5-year study period, 10271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses. Depending on the case definition, 160 to 519 household exposures to pertussis were identified. In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis. Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of greater than or equal to 7 days duration caused by Bordetella pertussis was 84% (95% confidence interval [CI] = 65-93) and that of DTaP was 58% (95% CI = 30-75). Using similar criteria, the efficacy against typical pertussis (greater than or equal to 21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95% CI = 77-99) and 86% (95% CI = 62-95) for DTP and DTaP, respectively. The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32-69) and 38% (95% CI = 13-56) for DTP and DTaP, respectively. CONCLUSION: This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy. Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness. When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines.

A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine.

BACKGROUND: The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. DESIGN: In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. RESULTS: From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussis infections with cough >/=7 days duration was 83% (95% confidence interval [CI]: 76-88) and 72% (95% CI: 62-79) for DTP and DTaP, respectively; results for DTP and DTaP based on >/=21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89-96) and 83% (95% CI: 76-88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough >/=7 days and 85% vs 76% for cough >/=21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough >/=7 days and 93% vs 93% for cough >/=21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussis infection (point estimate for cough >/=7 days: 31% [95% CI: -10-56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. CONCLUSIONS: Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussis infections. Interestingly, it also may have some efficacy against B parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country.

Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany.

The polymerase chain reaction (PCR) was recently added to conventional culture and serology for the diagnoses of Bordetella pertussis infection in a large vaccine efficacy trial in Germany. In vaccinees or family members who had illnesses with cough, two nasopharyngeal swabs (calcium alginate for culture and Dacron for PCR) were taken and initial and follow-up clinical data were obtained. PCR was done using oligonucleotide primers PTp1 and PTp2 which amplify a 191-base pair DNA fragment of pertussis toxin operon. From December, 1993, to May, 1994, 555 pairs of swabs were processed; 28 grew B. pertussis and 9 grew B. parapertussis. Twenty-six of the 28 subjects with B. pertussis-positive cultures also had positive PCR results as did one of the 9 B. parapertussis cases and 82 additional samples were positive by PCR. PCR increased the identification of subjects with B. pertussis infections by almost 4-fold. Clinical characteristics were analyzed by laboratory category (Group 1, 28 culture-positive; Group 2, 82 culture-negative, PCR-positive; and Group 3, 436 culture- and PCR-negative). Group 1 subjects were more likely to have a diagnosis of definite or probable pertussis and to have paroxysmal cough, posttussive vomiting, whooping and a cough duration of > or = 4 weeks than Group 2 or 3 subjects. In contrast Group 2 subjects were more likely than Group 1 subjects to have had previous pertussis immunization or prior antibiotics. PCR identified many mild illnesses caused by B. pertussis that were not identified by culture.

Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis.

In conjunction with a pertussis vaccine efficacy trial in Germany, nasopharyngeal specimens were collected from May, 1992, to March, 1993, from patients with cough illnesses. Clinical data were obtained by initial and follow-up questionnaires. Bordetella parapertussis was isolated from 38 patients (mean age, 3.5 years; 68% girls). Clinical characteristics in these cases were compared with those of 76 patients (matched by age and sex) with illness caused by Bordetella pertussis during the same period. Findings were: (B. pertussis/B. parapertussis): cough > 4 weeks 57%/37% (P = 0.06); whoop 80%/59% (P = 0.07); whoop > 2 weeks 26%/18% (P = 0.05); paroxysms 90%/83% (P = 0.5); body temperature > or = 38 degrees C 9%/0% (P = 0.17); vomiting 47%/42% (P = 0.69); and mean leukocyte and lymphocyte counts 12,500/mm3 and 7600/mm3 (P < 0.0001) and 7800/mm3 and 3500/mm3 (P < 0.0001), respectively. Illness caused by B. parapertussis was typical of pertussis but less severe than that caused by B. pertussis. In contrast with B. pertussis infection, lymphocytosis is not a characteristic of B. parapertussis infection. This is most likely a result of the lack of production of lymphocytosis-promoting factor toxin by B. parapertussis.

Localization analysis of neuronal activities in benign rolandic epilepsy using magnetoencephalography.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical syndrome characterized by partial sensorimotor seizures with centrotemporal spikes. We report a detailed localization analysis of spontaneous magnetic brain activities in seven BECRS patients using magnetoencephalography (MEG). All patients had BECRS diagnosis with typical seizures and electroencephalographic findings and five patients had minor psychomotor deficits. MEG was recorded over both parieto-temporal regions using a 2x37-channel biomagnetic system. The collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave activity was increased in four hemispheres of three patients. Increased fast-wave activity was found in all five patients with minor neuropsychological deficits. The presence of increased fast-wave magnetic brain activity appeared to cause functional anomalies in the higher brain function processes. In the spike analysis, the dipoles of rolandic spikes which constantly manifested anterior positivity in direction were concentrated in the superior rolandic region in four cases and the inferior rolandic region in three cases. The localizations of increased slow- and fast-wave activities were identical with those of the spikes. The seizure profiles were frequently characterized by the spike locations. Source localizations of the focal brain activities and rolandic spikes by MEG will contribute to the different diagnosis and pathophysiological elucidation of BECRS.

Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial*.

OBJECTIVE: To assess the efficacy and tolerability of flupirtine in comparison with tramadol for the treatment of moderate to severe subacute low back pain (LBP). DESIGN AND METHODS: In this randomised, double-blind, parallel-group trial, 209 LBP patients, aged 18-65 years, were orally treated with flupirtine 100 mg (n = 105) vs. tramadol 50 mg (n = 104), both three times daily for 5-7 days. MAIN OUTCOME MEASURES: Patient assessment of pain intensity after 5-7 days (primary); physicians' global assessment of improvement in pain and functional capacity; adverse events. RESULTS: Flupirtine showed an overall pain-relieving efficacy comparable to tramadol. Mean LBP intensity after end of treatment dropped from 6.8 (95% CI: 6.5-7.0) to 2.8 (95% CI: 2.3-3.1) for flupirtine and from 6.9 (95% CI: 6.6-7.1) to 3.0 (95% CI: 2.6-3.4) for tramadol, corresponding to pain relief rates of 57% (95% CI: 51-63%) and 56% (95% CI: 50-62%) respectively (p = 0.796), indicating non-inferiority of flupirtine. All other efficacy endpoints supported equivalent efficacy. Adverse events (AEs) occurred significantly less in patients after flupirtine (33%) vs. tramadol (49%) (p = 0.02) and both the respective severity grading and the AE-related dropout rates were significantly lower after flupirtine than after tramadol (1% vs. 15%, p < 0.001). CONCLUSION: Flupirtine 100 mg three times daily was associated with a reduction in pain and improvements in functional capacity equivalent to that observed with tramadol 50 mg three times daily, and was better tolerated, when administered to patients with subacute back pain for one week. The limitations of this study were the lack of a placebo control and the short (7-day) duration of the study.

[Optimizing epilepsy therapy in children and adolescents with lamotrigine]. / Optimierung der Epilepsietherapie von Kindern und Jugendlichen mit Lamotrigin.

Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.