Purpose: To reach a broad consensus on case definitions, outcomes, and outcome measures that will ease future study design and facilitate comparison of data from different studies of infantile spasms ...and West syndrome.
Methods: Persons who had recently presented or published first‐author original research in this field were invited to participate in an e‐mail Delphi process and to invite other investigators or clinicians who they thought might participate.
Results: The process consisted of six rounds, anonymous except to the facilitator. In total, responses were received from 46 participants. The final statement was approved by 31 participants from 15 countries. It concluded that the primary clinical outcome, cessation of spasms, should denote absence of witnessed spasms from within 14 days of commencement of treatment, and for ≥28 consecutive days from the last witnessed spasm. Primary electroclinical outcome denotes cessation of spasms with resolution of hypsarrhythmia. West syndrome should be a defined subset of the syndrome of infantile spasms. An infantile spasms single‐spasm variant should be recognized. Ways are suggested of handling subtle spasms in the context of clinical studies. It proposes a standard for reporting modifying and atypical features of hypsarrhythmia, a minimal set of baseline characteristics and outcomes that should be reported in trials of infantile spasms, and suggests a standard definition of relapse. Consensus was not reached on a definition of hypsarrhythmia.
Conclusions: We reached a clear consensus on many aspects of study design for the investigation of infantile spasms, although incomplete consensus was found on how to define EEG criteria.
Summary Background Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used ...treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone. Methods In this multicentre, open-label randomised trial, 102 hospitals (Australia three, Germany 11, New Zealand two, Switzerland three, and the UK 83) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27. Findings Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1–24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment. Interpretation Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up. Funding The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich.
Treatment of infantile spasms Hancock, Eleanor C; Osborne, John P; Edwards, Stuart W
Cochrane database of systematic reviews,
06/2013
6
Journal Article
Recenzirano
Odprti dostop
Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure-the spasms-and an electroencephalographic (EEG) abnormality often called hypsarrhythmia. ...Psychomotor retardation is frequently found at follow-up. Approximately two-thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms, and treatment remains problematic.
To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality.
To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles.To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences.
All randomised controlled trials (RCTs) of the administration of drug therapy to patients with infantile spasms.
Data collection from all relevant publications was independently undertaken by three review authors (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity.
We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms.
To date, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin, but this may or may not translate into better long-term outcomes. If prednisolone or vigabatrin is used, high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important, but this has not been proven. Further research using large studies with robust methodology is required.
Objective
To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment.
Methods
Identification of the underlying etiology and ...response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD‐10).
Results
A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval CI 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi‐square 4.3, P = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P = .037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi‐square 0.35, P = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead‐time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy.
Significance
This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.
Summary
Purpose: Infantile spasms is a severe infantile seizure disorder. Several factors affect developmental outcome, especially the underlying etiology of the spasms. Treatment also affects ...outcome. Both age at onset of spasms and lead time to treatment (the time from onset of spasms to start of treatment) may be important. We investigated these factors.
Methods: Developmental assessment using Vineland Adaptive Behaviour Scales (VABS) at 4 years of age in infants enrolled in the United Kingdom Infantile Spasms Study. Date of or age at onset of spasms was obtained prospectively. Lead time to treatment was then categorized into five categories. The effects of lead time to treatment, age of onset of spasms, etiology, and treatment on developmental outcome were investigated using multiple linear regression.
Key Findings: Age of onset ranged (77 infants) from <1 to 10 months (mean 5.2, standard deviation 2.1). Lead time to treatment was 7 days or less in 11, 8–14 days in 16, 15 days to 1 month in 8, 1–2 months in 15, >2 months in 21 and not known in 6. Each month of reduction in age at onset of spasms was associated with a 3.1 95% confidence interval (CI) 0.64–5.5, p = 0.03 decrease, and each increase in category of lead time duration associated with a 3.9 (95% CI 7.3–0.4, p = 0.014) decrease in VABS, respectively. There was a significant interaction between treatment allocation and etiology with the benefit in VABS in those allocated steroid therapy being in children with no identified etiology (coefficient 29.9, p = 0.004).
Significance: Both prompt diagnosis and prompt treatment of infantile spasms may help prevent subsequent developmental delay. Younger infants may be more at risk from the epileptic encephalopathy than older infants.
Light from the environment is important for vision and regulating various biological processes. Providing supplemental lighting in the stall area could allow for individually targeted or group-level ...control of light. This study aimed to determine whether dairy cattle had preferences for short-term exposure to white (full-spectrum) light-emitting diode (LED) light or no LED light, yellow-green or white LED light, and blue or white LED light in the stall area. In total, 14 lactating cows were housed in a free-stall pen with unrestricted access to 28 stalls. LED light was controlled separately for each side of the stall platform. Two combinations of light were tested per week, and each week consisted of three adaptation days and four treatment days. Lying behaviour and video data were recorded continuously using leg-mounted pedometers and cameras, respectively. Preference was assessed by the amount of time spent lying and the number of bouts under each light treatment. No differences occurred between treatments within each week for daily lying time and number of bouts. Similarly, no differences occurred between treatments within each time period. Further controlled studies of long-term exposure to different LED wavelengths and intensities are required to determine potential benefits on metabolic processes.
To examine the underlying etiology of infantile spasms from the United Kingdom Infantile Spasms Study (UKISS), using the pediatric adaptation of ICD 10.
Infants were enrolled in a randomized ...controlled trial or a parallel epidemiologic study. Etiological information included history, examination, and investigations. The infants were classified as proven etiology, if a neurologic disease was identified; as no identified etiology, if no neurologic disease was identified; and as not fully investigated, if a major piece of information was missing. Proven etiology was subclassified using the pediatric adaptation of ICD 10. The results were then examined to identify further methods of classification.
Of 207 infants, 127 (61%) had proven etiology, 68 (33%) had no identified etiology, and 12 (6%) were not fully investigated. Etiologies were prenatal in 63, perinatal in 38, postnatal in 8, and 18 other. The most common etiologies were: hypoxic-ischemic encephalopathy (HIE) 21 (10%), chromosomal 16 (8%), malformations 16 (8%), stroke 16 (8%), tuberous sclerosis complex (TSC) 15 (7%), and periventricular leukomalacia or hemorrhage 11 (5%). The remaining 32 etiologies were all individually uncommon. Response to treatment is given for individual etiologies.
Our method of classification allows the reporting of results by individual diseases, disease groups, or categories and is structured and clear. It avoids the use of poorly defined terms such as symptomatic and cryptogenic. It can adapt to new neurologic diseases, such as gene defects, and can be used for comparison of different groups of infants, thereby aiding meta-analysis.
Trauma patients are at high risk for life-threatening venous thromboembolic (VTE) events. We examined the relationship between prophylactic inferior vena cava (IVC) filter use, mortality, and VTE.
...The prevalence of prophylactic placement of IVC filters has increased among trauma patients. However, there exists little data on the overall efficacy of prophylactic IVC filters with regard to outcomes.
Trauma quality collaborative data from 2010 to 2014 were analyzed. Patients were excluded with no signs of life, Injury Severity Score <9, hospitalization <3 days, or who received IVC filter after occurrence of VTE event. Risk-adjusted rates of IVC filter placement were calculated and hospitals placed into quartiles of IVC filter use. Mortality rates by quartile were compared. We also determined the association of deep venous thrombosis (DVT) with the presence of an IVC filter, accounting for type and timing of initiation of pharmacological VTE prophylaxis.
A prophylactic IVC filter was placed in 803 (2%) of 39,456 patients. Hospitals exhibited significant variability (0.6% to 9.6%) in adjusted rates of IVC filter utilization. Rates of IVC placement within quartiles were 0.7%, 1.3%, 2.1%, and 4.6%, respectively. IVC filter use quartiles showed no variation in mortality. Adjusting for pharmacological VTE prophylaxis and patient factors, prophylactic IVC filter placement was associated with an increased incidence of DVT (OR = 1.83; 95% CI, 1.15-2.93, P-value = 0.01).
High rates of prophylactic IVC filter placement have no effect on reducing trauma patient mortality and are associated with an increase in DVT events.
Infantile spasms is a severe infantile seizure disorder that is difficult to treat and has a high morbidity. Absence of spasms on days 13 and 14 after randomisation is more common in infants ...allocated hormone treatments than in those allocated vigabatrin. We sought to assess whether early control of spasms is associated with improved developmental or epilepsy outcomes.
Infants enrolled in the United Kingdom Infantile Spasms Study (UKISS) were randomly assigned hormone treatment (n=55) or vigabatrin (n=52) and were followed up until clinical assessment at 12–14 months of age. We assessed neurodevelopment with the Vineland adaptive behaviour scales (VABS) at 14 months of age on an intention to treat basis.
Of 107 infants enrolled, five died and 101 survivors reached both follow-up assessments. Absence of spasms at final clinical assessment (hormone 41/55 75%
vs vigabatrin 39/51 76%) was similar in each treatment group (difference 1·9%, 95% CI −18·3% to 14·4%; χ
2=0·05; p=0·82). Mean VABS score did not differ significantly (hormone 78·6 SD 16·8
vs vigabatrin 77·5 SD 12·7; difference 1·0, 95% CI −4·9 to 7·0;
t
99
=0·35, p=0·73). In infants with no identified underlying aetiology, the mean VABS score was higher in those allocated hormone treatment than in those allocated vigabatrin (88·2 17·3
vs 78·9 14·3; difference 9·3, 95% CI 1·2 to 17·3;
t
95
=2·28, p=0·025).
Hormone treatment controls spasms better than does vigabatrin initially, but not at 12–14 months of age. Better initial control of spasms by hormone treatment in those with no identified underlying aetiology may lead to improved developmental outcome.
OBJECTIVES
To report the frequency of renal symptoms and complications of patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic appearance of the kidneys in a ...population‐based sample, and to investigate the relationship between a history of renal haemorrhage and renal lesions identified by ultrasonography.
PATIENTS AND METHODS
As part of an epidemiological study, 179 patients with TSC were identified as living in the Wessex Region in the South of England. Patients were interviewed and examined in their homes, to elicit the presence of renal symptoms or a history of renal complications. Renal ultrasonography was used in consenting patients in their homes.
RESULTS
There was a history of renal complications in 16 (9%) patients; 149 consented to interview and examination, and 19 gave a history of renal symptoms in the previous year; 124 had renal ultrasonography; 86 (69%) had renal angiomyolipomas and 37 (30%) had renal cysts. Large lesions (>3 cm in diameter) were strongly associated with a history of symptomatic bleeding, although significant haemorrhage occurred in a 6‐year‐old child with small angiomyolipomas.
CONCLUSIONS
The formation of angiomyolipoma in TSC is common. Polycystic kidney disease, renal carcinoma and renal failure, although rare, occur in TSC. Most patients with angiomyolipomas have neither complications nor symptoms. There was no appreciable difference between the sexes in the risk of developing these lesions. Although less commonly seen in the very young, there is no identifiable relationship after adolescence between age and the risk of having a renal angiomyolipoma. Bleeding tends to occur from large lesions (>3 cm) but most such patients have remained asymptomatic to date.
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