Summary Background Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a ...population of community-dwelling older people. Methods In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70–78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score ALDS) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. Findings Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio HR 0·92, 95% CI 0·71–1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 SD 6·8 in the intervention group and 85·7 7·1 in the control group; adjusted mean difference −0·02, 95% CI −0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80–1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 19% of 1469 participants in the intervention group and 228 17% of 1307 participants in the control group; HR 1·06, 95% CI 0·86–1·31; p=0·57). Interpretation A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations. Funding Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development.
Summary Background Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the ...haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. Methods We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. Findings Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18–3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. Interpretation Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. Funding The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.
Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral ischemia is considered to be caused by ...vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not successful in preventing ischemia. The purpose of this review is to give an overview of clinical data showing that DCI cannot always be attributed to vasospasm, and to present an in-depth analysis of clinical and autopsy studies on the role of microthrombosis in the pathogenesis of DCI. Clinical studies show that DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, impaired fibrinolytic activity, and inflammatory and endothelium-related processes, lead to the formation of microthrombi, which ultimately result in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in the pathophysiology of DCI is crucial for the development of effective therapies against this complication. Because multiple pathways are involved, future research should focus on drugs with pleiotropic effects.
Summary Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study ...aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. Methods In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. Findings Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio OR 1·2, 95% CI 0·3–4·4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushing's face occurred more often in the prednisolone group. Interpretation Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. Funding The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.
High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ...ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe.
Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily) in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability.
There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24) and the five ascorbic acid-treated (19, 14 to 24) patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, P = 0.11) or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication.
Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe.
Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral ...haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.
The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.
To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains unknown. Besides vasospasm, microthrombosis might have an important function. As in patients ...with thrombotic thrombocytopenic purpura an A Disintegrin And Metalloprotease with ThromboSpondin repeats-13 (ADAMTS13) deficiency leads to higher concentrations of large von Willebrand factor (vWF) multimers resulting in microthrombosis, our purpose was to compare ADAMTS13 and vWF in patients with and without DCI after aneurysmal SAH. We measured ADAMTS13 activity, vWF antigen, vWF propeptide, and vWF ristocetin cofactor activity in plasma at standard intervals. Thirty-one patients were included. Eleven patients (35%) developed DCI. No differences were observed in baseline characteristics between patients with and without DCI. Patients with DCI had a stronger decrease in ADAMTS13 activity, and a more profound increase in vWF antigen, vWF propeptide, and vWF activity in the first few days after the hemorrhage (P-values for difference in polynomial time trend 0.0001, 0.020, 0.004, and 0.188, respectively). No indication of correlation between vWF antigen and ADAMTS13 was found (r=−0.027, P=0.736). Our results suggest that microthrombosis has a role in the pathogenesis of DCI, as a result of decreased ADAMTS13 activity and endothelium dysfunction.
Chart review of 41 adult patients with group A streptococcal (GAS) meningitis in The Netherlands revealed that this is a community-acquired disease and occurs mainly in patients with predisposing ...factors: of the 41 patients in this case series, 24 (60%) of 40 evaluable patients had otitis or sinusitis. Fever and neck stiffness were the most common clinical manifestations of disease, but, in addition, high rates of seizures (12 32% of 38 patients), focal neurological findings (13 36% of 36 patients), and hyponatremia (20 58% of 35 patients) were found. In contrast with data from the literature that describes 27 adult cases, we found that GAS meningitis is a fulminant disease with a mortality rate of 27% (10 of 37 patients), and that neurological sequelae occur in 36% (12 of 38) of surviving patients.
Background
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled ...studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since been updated, most recently in 2013.
Objectives
To review systematically the evidence from randomised controlled trials (RCTs) concerning the efficacy and safety of IVIg in CIDP.
Search methods
On 4 December 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, issue 11 in the Cochrane Library), MEDLINE and EMBASE to December 2012 and ISI from January 1985 to May 2008. We searched for ongoing trials through two metaRegistries (World Health Organization International Clinical Trials Registry Platform Search Portal and Current Controlled Trials).
Selection criteria
We selected RCTs testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP.
Data collection and analysis
Two authors reviewed literature searches to identify potentially relevant RCTs, scored their quality and extracted data independently. We contacted authors for additional information.
Main results
We considered eight RCTs, including 332 participants, to be eligible for inclusion in the review. These trials were homogeneous and the overall risk of bias low. Five studies, in a total of 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange, one trial compared IVIg with prednisolone in 32 participants, and one trial, newly included at this update, compared IVIg with intravenous methylprednisolone in 46 participants.
A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome 3.03 (95% CI 2.33 to 4.55), high quality evidence). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials, including 84 participants, the disability score could be transformed to the modified Rankin score, on which improvement of one point after IVIg treatment compared to placebo was barely significant (RR 2.40, 95% CI 0.98 to 5.83) (moderate quality evidence). Only one placebo‐controlled study included in this review had a long‐term follow‐up. The results of this study suggest that IVIg improves disability more than placebo over 24 and 48 weeks.
The mean disability score revealed no significant difference between IVIg and plasma exchange at six weeks (moderate quality evidence). There was no significant difference in improvement in disability on prednisolone compared with IVIg after two or six weeks, or on methylprednisolone compared to IVIg after two weeks or six months (moderate quality evidence).
There were no statistically significant differences in frequencies of side effects between the three types of treatment for which data were available (IVg versus placebo or steroids). (moderate or high quality evidence) Mild and transient adverse events were found in 49% of participants treated with IVIg, while serious adverse events were found in six per cent.
Authors' conclusions
The evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of three. During this period it has similar efficacy to plasma exchange, oral prednisolone and intravenous methylprednisolone. In one large trial, the benefit of IVIg persisted for 24 and possibly 48 weeks. Further research is needed to compare the long‐term benefits as well as side effects of IVIg with other treatments.
PDF
