European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage.

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.

Electrical Somatosensory Stimulation in Early Rehabilitation of Arm Paresis After Stroke: A Randomized Controlled Trial.

BACKGROUND: Arm paresis is present in 48% to 77% of acute stroke patients. Complete functional recovery is reported in only 12% to 34%. Although the arm recovery is most pronounced during the first 4 weeks poststroke, few studies examined the effect of upper extremity interventions during this period. OBJECTIVE: To investigate the effect of electrical somatosensory stimulation (ESS) delivered during early stroke rehabilitation on the recovery of arm functioning. METHODS: A total of 102 patients with arm paresis were randomized to a high-dose or a low-dose ESS group within 7 days poststroke according to our sample size estimation. The high-dose group received 1-hour ESS to the paretic arm daily during hospitalization immediately followed by minimum 15-minute task-oriented arm training that was considered a component of the usual rehabilitation. The low-dose group received a placebo ESS followed by identical training. Primary outcome-Box and Block Test (BBT); secondary outcomes-Fugl-Meyer Assessment (FMA), grip strength, pinch strength, perceptual threshold of touch, pain, and modified Rankin Scale (mRS); all recorded at baseline, postintervention and at 6 months poststroke. RESULTS: There were no differences between the high-dose and the low-dose groups for any outcome measures at any time points. Improvements ⩾ minimal clinically important difference were observed for FMA, hand grip strength, and mRS in both groups. CONCLUSIONS: Providing the present ESS protocol prior to arm training was equally beneficial as arm training alone. These results are valid for patients with mild-to-moderate stroke and moderate arm impairments. We cannot exclude benefits in patients with other characteristics, in other time intervals poststroke or using a different ESS protocol. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02250365).

Use of References in Responses from Scandinavian Drug Information Centres.

Background: The aim of this study was to compare use of references in responses from Scandinavian drug information centres (DICs). Methods: Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The six queries concerned adverse effects, pharmacokinetics, pregnancy, complementary medicine, polypharmacy, and breast feeding. References in the responses were categorised into five types of drug information sources: primary (original studies), secondary (reviews), tertiary (drug monographs, handbooks, etc.), DIC database, or personal communication. Results: Two hundred and forty-four references were used in the 42 responses. The mean number of references varied from 3.0 to 10.6 for the six queries. The largest difference between centres with regard to number of references used (range 1⁻17) was found for the query on complementary medicine. In total, 124 references (50.8%) were tertiary, and only 10 of the 42 responses (23.8%) did not have any tertiary references included. Complementary medicine, breast feeding, and pregnancy were query types associated with relatively frequent use of primary references. Use of DIC database was not uncommon, but personal communications were seldom used. Conclusions: Scandinavian DICs differ substantially in number and type of references to identical drug-related queries. Tertiary sources are mainly preferred irrespective of type of query.

Electrical somatosensory stimulation followed by motor training of the paretic upper limb in acute stroke: study protocol for a randomized controlled trial.

BACKGROUND: Upper limb paresis is one of the most frequent and persistent impairments following stroke. Only 12-34% of stroke patients achieve full recovery of upper limb functioning, which seems to be required to habitually use the affected arm in daily tasks. Although the recovery of upper limb functioning is most pronounced during the first 4 weeks post stroke, there are few studies investigating the effect of rehabilitation during this critical time window. The purpose of this trial is to determine the effect of electrical somatosensory stimulation (ESS) initiated in the acute stroke phase on the recovery of upper limb functioning in a nonselected sample of stroke patients. METHODS/DESIGN: A sample of 102 patients with upper limb paresis of varying degrees of severity is assigned to either the intervention or the control group using stratified random sampling. The intervention group receives ESS plus usual rehabilitation and the control group receives sham ESS plus usual rehabilitation. The intervention is applied as 1 h of ESS/sham ESS daily, followed by motor training of the affected upper limb. The ESS/sham ESS treatment is initiated within 7 days from stroke onset and it is delivered during hospitalization, but no longer than 4 weeks post stroke. The primary outcome is hand dexterity assessed by the Box and Block Test; secondary outcomes are the Fugl-Meyer Assessment, hand grip strength, pinch strength, perceptual threshold of touch, degree of pain, and modified Rankin Scale score. Outcome measurements are conducted at baseline, post intervention and at 6-month follow-up. DISCUSSION: Because of the wide inclusion criteria, we believe that the results can be generalized to the larger population of patients with a first-ever stroke who present with an upper limb paresis of varying severity. On the other hand, the sample size (n = 102) may preclude subgroup analyses in such a heterogeneous sample. The sham ESS treatment totals a mere 2% of the active ESS treatment delivered to the intervention group per ESS session, and we consider that this dose is too small to induce a treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02250365 . Registered on 18 September 2014.

Immunomodulating potential of supplementation with probiotics: a dose-response study in healthy young adults.

Certain probiotic microorganisms have been found beneficial in the treatment of immune-related diseases and may also affect immune function in healthy people. Intervention studies of probiotics in healthy humans are urgently required. Here, the immunomodulating potential of Bifidobacterium animalis ssp. lactis (BB-12) and Lactobacillus paracasei ssp. paracasei (CRL-431) was studied in a double-blind placebo-controlled parallel dose-response trial (n=71) based on five randomly assigned groups of young healthy adults supplemented for 3 weeks with 0, 10(8), 10(9), 10(10) and 10(11) CFU day(-1), respectively, of a mixture of BB-12 and CRL-431. No statistically significant dose-dependent effect was found for phagocytic activity in blood leukocytes, fecal immunoglobulin A (IgA) concentrations or production of interferon-gamma and interleukin-10 in blood cells. When evaluating data according to the amount of viable BB-12 recovered from faeces, the interferon-gamma production in blood cells was significantly reduced. In conclusion, no solid effect on the immune function of young healthy adults supplemented with even high doses of B. animalis ssp. lactis BB-12 and L. paracasei ssp. paracasei CRL-431 was demonstrated in this study.