Inhibitor development after liver transplantation in congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.

Quality of life in patients with transfusion-dependent thalassemia after hematopoietic SCT.

In this cross-sectional study, we compared the quality of life (QOL) in transfusion-dependent thalassemic patients who survived matched sibling hematopoietic SCT (HSCT, n=24) with patients treated conventionally with transfusion and iron chelation (n=74). WHOQOL-BREF(HK) and PedsQL questionnaires were administered to patients aged >18 years and 5-12 years, respectively. Patients aged 12-18 years received both questionnaires. WHOQOL-BREF(HK) revealed post transplant patients rated overall health better than those treated conventionally (score 3.67 vs 3.06, P=0.01). They are less dependent on medical aids (3.87 vs 2.96, P=0.006), having higher activity level (4.00 vs 3.36, P=0.026) and better personal relationships (4.13 vs 3.69, P=0.014). Physical health domain score was better (75.20 vs 63.94, P=0.007). These differences remained significant after adjustment for comorbidities. PedsQL revealed post transplant patients rated better for running (3.53 vs 2.72, P=0.001) and sports (3.20 vs 2.64, P=0.038), even after adjustment for comorbidities, but were less satisfied for school absence to attend hospital (2.53 vs 3.29, P=0.03). Post transplant patients were significantly more likely to consider marriage (100 vs 75.7%, P=0.033), but not childbearing (66.7 vs 51.4%, P=0.28). In conclusion, transplanted thalassemic patients enjoy better QOL, mainly in physical health, compared with conventionally treated patients. This information is important to patients considering HSCT.

Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation.

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age < or =2 years at transplant (odds ratio (OR)=5.25, P=0.011), BU-CY conditioning (OR=5.16, P=0.001), thalassemia major (OR=3.97, P=0.015), platelet engraftment beyond day +21 (OR=8.67, P=0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P=0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR)=23.6, P=0.006), hepatic and cutaneous GVHD (HR=8.15, P=0.038), maximal weight gain >9% (HR=6.81, P=0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 micromol l(-1) (HR=13.6, P=0.016), day +21 bilirubin >200 micromol l(-1) (HR=33.9, P=0.001), and rise of bilirubin >15 micromol l(-1) per day within the first week (HR=19.8, P=0.006). Mortality was substantially higher if >3 predictors were present (HR=33.9, P=0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.

Acupuncture for insomnia.

BACKGROUND: Although conventional non-pharmacological and pharmacological treatments for insomnia are effective in many people, alternative therapies such as acupuncture are still widely practiced. However, it remains unclear whether the existing evidence is rigorous enough to support its use. OBJECTIVES: To determine the efficacy and safety of acupuncture in people with insomnia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts International, CINAHL, AMED (the Allied and Complementary Medicine Database), TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System), National Center for Complementary and Alternative Medicine, the National Institute of Health Clinical Trials Database, the Chinese Acupuncture Trials Register, the Trials Register of the Cochrane Complementary Medicine Field, from inception to 2006, and the sleep bibliography, which is available at www.websciences.org/bibliosleep. We searched reference lists of retrieved articles, and contacted trial authors and experts in the field for information on ongoing/completed trials. SELECTION CRITERIA: Randomised controlled trials evaluating any form of acupuncture involving participants of any age with any type of insomnia were included. Included trials compared acupuncture with placebo or sham or no treatment, or acupuncture plus other treatments compared with the same other treatments. Trials that compared only acupuncture methods or compared acupuncture alone against other treatments alone were excluded, since they did not yield the net effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed quality according to a set of criteria for risk of selection bias, performance bias, attrition bias and detection bias. Relative risk (RR) and standardised mean difference (SMD) with 95% confidence intervals were used for binary and continuous outcomes respectively. Data were combined in meta-analyses (on an intention-to-treat basis), where more than one trial without significant clinical heterogeneity presented the same outcome. MAIN RESULTS: Seven trials met the inclusion criteria. The studies included 590 participants with insomnia, of whom 56 dropped out. Participant age ranged from 15 to 98 years, and the duration of insomnia varied from 6 months to 19 years. Co-existing medical conditions contributing to insomnia included stroke, end-stage renal disease and pregnancy. Apart from conventional needle acupuncture, different variants of acupuncture such as acupressure, auricular magnetic and seed therapy, and transcutaneous electrical acupoint stimulation (TEAS) were evaluated. Meta-analysis was limited because of considerable heterogeneity between comparison groups and between outcome measures. Based on the findings from individual trials, the review suggested that acupuncture and acupressure may help to improve sleep quality scores when compared to placebo (SMD = -1.08, 95% CI = -1.86 to -0.31, p=0.006) or no treatment (SMD -0.55, 95% CI = -0.89 to -0.21, p=0.002). TEAS also resulted in better sleep quality score in one trial (SMD = -0.74, 95% CI = -1.22 to -0.26, p=0.003). However, the efficacy of acupuncture or its variants was inconsistent between studies for many sleep parameters, such as sleep onset latency, total sleep duration and wake after sleep onset. The combined result from three studies reporting subjective insomnia improvement showed that acupuncture or its variants was not more significantly effective than control (RR = 1.66, 95% CI = 0.68 to -4.03) and significant statistical heterogeneity was observed. Only one study reported an adverse event, with one out of 16 patients (6.3%) withdrawing from acupuncture because of pain. AUTHORS' CONCLUSIONS: The small number of randomised controlled trials, together with the poor methodological quality and significant clinical heterogeneity, means that the current evidence is not sufficiently extensive or rigorous to support the use of any form of acupuncture for the treatment of insomnia. Larger high quality clinical trials employing appropriate randomisation concealment and blinding with longer follow-up are needed to further investigate the efficacy and safety of acupuncture for the treatment of insomnia.

Surgery for scoliosis in Duchenne muscular dystrophy.

BACKGROUND: Scoliosis in people with Duchenne muscular dystrophy is usually progressive and treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most people with Duchenne muscular dystrophy and scoliosis. OBJECTIVES: The objectives of this systematic review were to determine the effectiveness and safety of spinal surgery in Duchenne muscular dystrophy patients with scoliosis. We intended to test whether spinal surgery is effective in increasing life expectancy, improving respiratory function, improving quality of life and overall functioning; and whether spinal surgery is associated with severe adverse effects. SEARCH STRATEGY: We searched the specialized registers of the Cochrane Neuromuscular Disease Group and Cochrane Back Group, the Cochrane Central Register of Controlled Trials (January 2006), MEDLINE (January 1966 to January 2006), EMBASE (January 1980 to January 2006), Dissertation Abstracts International (1861 to Jan 2006), CINAHL (January 1982 to January 2006), and the National Institute of Health Clinical Trials Database (January 2006). No language restrictions were imposed. SELECTION CRITERIA: Controlled clinical trials using random or quasi-random allocation of treatment evaluating all forms of spinal surgery for scoliosis in patients with Duchenne muscular dystrophy were to be included in the review. The control interventions would have been no treatment, non-operative treatment, or a different form of spinal surgery. DATA COLLECTION AND ANALYSIS: Two authors examined the search results and evaluated the study characteristics against inclusion criteria to decide which ones would be included in the review. MAIN RESULTS: A total of 402 studies were identified from electronic searching. Thirty-six studies were relevant but none met the inclusion criteria for the review, because they were not clinical trials but prospective or retrospective reviews of case series. AUTHORS' CONCLUSIONS: Since there were no randomized controlled clinical trials available to evaluate the effectiveness of scoliosis surgery in people with Duchenne muscular dystrophy, no evidence-based recommendation can be made for clinical practice. Patients should be informed about the uncertainty of benefits and potential risks of surgery for scoliosis. Randomized controlled trials are needed to investigate the effectiveness of scoliosis surgery, in terms of patients' quality of life, functional status, respiratory function and life expectancy.

Acupuncture for epilepsy.

BACKGROUND: Seizures are poorly controlled in many people with epilepsy despite adequate current antiepileptic treatments. There is increasing interest in alternative therapies such as acupuncture; however, it remains unclear whether the existing evidence is rigorous enough to support the use of acupuncture. OBJECTIVES: To determine the effectiveness and safety of acupuncture in people with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (June 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005). We also searched MEDLINE, EMBASE, CINAHL, AMED, TCMLARS, China Biological Medicine Database, Chinese Acupuncture Trials Register, National Center for Complementary and Alternative Medicine, and National Institute of Health Clinical Trials Database from inception to June 2005. Reference lists from relevant trials were reviewed. No language restrictions were imposed. SELECTION CRITERIA: Randomised controlled trials evaluating any form of acupuncture involving people of any age with any type of epilepsy were included. Trials included were those comparing acupuncture with placebo, sham or no treatment; or comparing acupuncture plus other treatments with the same other treatments. Trials that only compared different acupuncture methods or compared acupuncture alone with other treatments were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed trial quality using the Jadad score. Relative risk (RR) was used for binary data and weighted mean difference for continuous data, and 95% confidence intervals are given. Where possible, analyses were by intention to treat. MAIN RESULTS: Three small trials of varying methodological quality and with short follow up met the inclusion criteria. Two studied children in China and one studied adults in Norway. The two Chinese studies compared acupuncture plus Chinese herbs with Chinese herbs alone while the Norwegian study compared acupuncture with sham acupuncture. The two Chinese studies found that more children treated with acupuncture achieved 75% or greater reduction in seizure frequency (RR 1.52, 95% CI 1.12 to 2.05) and seizure duration (RR 2.38, 95% CI 1.13 to 5) with a significant 50% or greater reduction in seizure duration (RR 1.36, 95% CI 1.07 to 1.73). However, the two trials were of low quality without adequate description of randomisation method, concealment of randomisation or blinding. On the other hand, the higher quality Norwegian trial found that acupuncture did not improve the mean seizure frequency, seizure-free weeks, or quality of life in adults. AUTHORS' CONCLUSIONS: The current evidence does not support acupuncture as a treatment for epilepsy. Much larger high quality clinical trials employing appropriate controls are needed.

Complementary and miscellaneous interventions for nocturnal enuresis in children.

BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults. OBJECTIVES: To assess the effects of complementary interventions and others such as surgery or diet on nocturnal enuresis in children, and to compare them with other interventions. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register (searched 22 November 2004), the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (January 1984 to June 2004) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised trials of complementary and other miscellaneous interventions for nocturnal enuresis in children were included except those focused solely on daytime wetting. Comparison interventions could include no treatment, placebo or sham treatment, alarms, simple behavioural treatment, desmopressin, imipramine and miscellaneous other drugs and interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: In 15 randomised controlled trials, 1389 children were studied, of whom 703 received a complementary intervention. The quality of the trials was poor: four trials were quasi-randomised, five showed differences at baseline and ten lacked follow up data. The outcome was better after hypnosis than imipramine in one trial (relative risk (RR) for failure or relapse after stopping treatment 0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy appeared to be better in terms of fewer children failing or relapsing than both alarm (RR 0.28, 95% CI 0.09 to 0.85) and rewards (0.29, 95% 0.09 to 0.90) but this depended on data from only one trial. Acupuncture had better results than sham control acupuncture (RR for failure or relapse after stopping treatment 0.67, 95% CI 0.48 to 0.94) in a further trial. Active chiropractic adjustment had better results than sham adjustment (RR for failure or relapse after stopping treatment 0.74, 95% CI 0.60 to 0.91). However, each of these findings came from small single trials, and need to be verified in further trials. The findings for diet and faradization were unreliable, and there were no trials including homeopathy or surgery. AUTHORS' CONCLUSIONS: There was weak evidence to support the use of hypnosis, psychotherapy, acupuncture and chiropractic but it was provided in each case by single small trials, some of dubious methodological rigour. Robust randomised trials are required with efficacy, cost-effectiveness and adverse effects carefully monitored.

Accupouncture for acute management and rehabilitation of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the severity of the insult to the brain. It can also cause a range of debilitating sequelae which require cognitive, motor, communication, emotional, or behavioral rehabilitation of varying intensity and duration. A number of studies conducted and published in China have suggested that acupuncture may be beneficial in the acute treatment and rehabilitation of TBI. The aim of this paper was to determine the efficacy and safety of acupuncture in the acute management or rehabilitation (or both) of patients with a TBI, including cognitive, neurological, motor, communication, emotional, or behavioral complications, or a combination of such complications. METHODS: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials 2008, Issue 2 (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese Acupuncture Studies Register, the Studies Register of the Cochrane Complementary Medicine Field, NCCAM, and NIH Clinical Studies Database. Three major Mainland Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also searched using keywords in simplified Chinese. Searches were completed in December 2009. Randomized controlled studies evaluating different variants of acupuncture and involving participants of any age who had suffered a TBI. Included trials compared acupuncture with placebo or sham treatment, or acupuncture plus other treatments compared with the same other treatments.We excluded trials that only compared different variants of acupuncture or compared acupuncture alone against other treatments alone, as they did not yield the net effect of acupuncture. Two review authors identified potential articles from the literature search and extracted data independently using a data extraction form. We performed methodological assessment of included studies using the Cochrane Collaboration's tool for assessing risk of bias. We were unable to perform quantitative data analysis due to insufficient included studies and available data. RESULTS: Four RCTs, including 294 participants, reported outcomes specified by this review. Three investigated electro-acupuncture for TBI while one investigated acupuncture for acute TBI. The results seem to suggest that acupuncture is efficacious for these indications, however the low methodological quality of these studies renders the results questionable. No adverse effects of acupuncture were reported in any of the studies. CONCLUSIONS: The low methodological quality of the included studies does not allow us to make conclusive judgments on the efficacy and safety of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its beneficial role for these indications remains uncertain. Further research with high quality trials is required.

Attention-deficit hyperactivity disorder and blood mercury level: a case-control study in Chinese children.

OBJECTIVE: To investigate the association between blood mercury level and attention-deficit hyperactivity disorder (ADHD) in Chinese children in Hong Kong. METHODS: Fifty-two children with ADHD aged below 18 years diagnosed by DSM IV criteria without perinatal brain insults, mental retardation or neurological deficits were recruited from a developmental assessment center. Fifty-nine normal controls were recruited from a nearby hospital. Blood mercury levels were measured by cold vapor atomic absorption spectrophotometry. RESULTS: The mean ages of cases and controls were 7.06 and 7.81 years respectively. Boys predominated (case = 44 [84.6 %], control = 44 [74.6 %]). There was significant difference in blood mercury levels between cases and controls (geometric mean 18.2 nmol/L [95 % CI 15.4 - 21.5 nmol/L] vs. 11.6 nmol/L [95 % CI 9.9 - 13.7 nmol/L], p < 0.001), which persists after adjustment for age, gender and parental occupational status (p < 0.001). The geometric mean blood mercury level was also significantly higher in children with inattentive (19.4 nmol/L, 95 % CI 13.3 - 28.5 nmol/L) and combined (18.0 nmol/L, 95 % CI 14.9 - 21.8 nmol/L) subtypes of ADHD. Blood mercury levels were above 29 nmol/L in 17 (26.9 %) cases and 6 (10.2 %) controls. Children with blood mercury level above 29 nmol/L had 9.69 times (95 % CI 2.57 - 36.5) higher risk of having ADHD after adjustment for confounding variables. CONCLUSION: High blood mercury level was associated with ADHD. Whether the relationship is causal requires further studies.

A meta-analysis on intravenous magnesium sulphate for treating acute asthma.

AIM: To evaluate the effectiveness of intravenous magnesium sulphate in the treatment of acute asthmatic attacks in children by meta-analysis. METHODS: A systematic and comprehensive search of the literature was performed to identify controlled clinical trials of magnesium sulphate in paediatric acute asthma which evaluated outcomes of hospitalisation or short term pulmonary function tests or symptom scores. Unpublished data were searched by personal contacts with authors and specialists. Two reviewers independently assessed trial qualities and synthesised data. Heterogeneity among studies was evaluated by the Cochrane Q test. Outcome data were pooled by random or fixed effect models depending on presence or absence of heterogeneity. RESULTS: Five randomised placebo controlled trials involving a total of 182 patients were identified. They compared intravenous magnesium sulphate to placebo in treating paediatric patients with moderate to severe asthmatic attacks in the emergency department, with co-therapies of inhaled beta2 agonists and systemic steroids. The studies were of high quality with results judged to be valid. Four studies showed that magnesium sulphate was effective, while one study found it ineffective. There was no significant heterogeneity in the primary outcome of hospitalisation. In the fixed effect model, magnesium sulphate is effective in preventing hospitalisation (OR 0.290, 95% CI 0.143 to 0.589). The number needed to treat is 4 (95% CI 3 to 8). Secondary outcomes of short term pulmonary function tests and clinical symptom scores also showed significant improvement. CONCLUSION: Intravenous magnesium sulphate probably provides additional benefit in moderate to severe acute asthma in children treated with bronchodilators and steroids.

Use of midazolam and ketamine as sedation for children undergoing minor operative procedures.

OBJECTIVES: We used intravenous midazolam and ketamine for children undergoing minor operative procedures with satisfactory results. We aimed to further evaluate its efficacy and adverse effects in pediatric ward setting. METHODS: This was a prospective study of all children undergoing minor operations with sedation in our pediatric general and oncology wards from July 1998 to June 1999. The procedures included lumber puncture+/-intrathecal chemotherapy, bone marrow aspiration+/-trephine biopsy, central venous catheter removal, skin biopsy, or their combination. All sedation procedures were started with midazolam 0.1 mg/kg and ketamine 1 mg/kg; they were increased gradually to 0.4 and 4 mg/kg, respectively, if necessary. Heart rate and SaO2 were continuously monitored. RESULTS: Altogether, 369 minor operations were performed in 112 patients (male:female=2:1, median age 6 years, range 5 months-17 years). All achieved adequate sedation, with 96% within 30 s and 75% required just the starting dose. Younger children required a higher dosage (p=0.003 for midazolam, p<0.001 for ketamine). The median recovery time was 87 min, with no association with age, sex, or dosage of sedation, but was longer in patients having hallucination (p=0.001). Adverse effects included tachycardia (27.9%), increased secretion (17.6%), agitation (13.6%), nausea and vomiting (9.2%), hallucination (8.7%), desaturation (8.4%), and cataleptic reaction (0.8%). All desaturation episodes were transient and responded to oxygen supplement alone. None developed bronchospasm or convulsion. Some adverse effects were dose-related. Half of the children who received 0.3 mg/kg midazolam developed desaturation. CONCLUSIONS: Intravenous midazolam-ketamine can provide rapid, effective, and safe sedation for children undergoing minor operations in ward setting. Adverse effects are mild. Midazolam above 0.3 mg/kg should be used with caution.

Parents' understanding of their child's congenital heart disease.

OBJECTIVES: To assess parents' understanding of their child's congenital heart disease in various knowledge domains and to identify significant determinants of parental knowledge. DESIGN: Cross sectional questionnaire survey SETTING: Tertiary paediatric cardiac centre. PATIENTS: 156 parents of children with relatively simple congenital heart defects were recruited from the outpatient clinic of a tertiary cardiac centre over a three month period. The questionnaire comprised 10 items of knowledge under three domains: nature of heart disease and its treatment; impact of heart disease on exercise capacity; and infective endocarditis and its prevention. The frequency distribution of the parents' knowledge in the different domains was determined. Univariate analyses and logistic regression were performed to identify significant determinants of knowledge in selected items. RESULTS: While 59% of parents correctly named their child's congenital heart disease, only 28.8% correctly indicated the heart lesion(s) diagrammatically. However, more than 80% of parents were aware of the indications and aims of previous surgical and transcatheter interventions. About half of the parents were aware of possible aetiologies and of the hereditary nature and symptoms attributable to underlying heart disease. Disappointingly, of the 56 parents whose children were taking cardiac medications, only 25 (44.6%) and 4 (7.1%) knew correctly the functions and important side effects of the medications, respectively. With regard to exercise capacity, 59% of parents indicated its level appropriate for the heart lesion. While 26.9% of parents had heard of the term "infective endocarditis", slightly more than half of the parents were aware of the need for antibiotics before dental procedures. Significant determinants of knowledge in the nature of heart disease were cardiac diagnosis, occupation of parents, and their educational level. Logistic regression failed to identify any significant determinants of parental knowledge in the other two domains. CONCLUSIONS: Parents of children with congenital heart disease have important knowledge gaps. Our findings suggest that the current educational programme is inadequate and needs to be refined to promote better parental understanding of their child's heart disease, with the ultimate aim of enabling parents to impart such knowledge accurately to their children.