Quality care close to home: Objectives and early outcomes of a second paediatric heart transplant service in Australia.

AIM: We describe the experience of a new paediatric heart transplant (HT) centre in Australia. New South Wales offers quaternary paediatric cardiac services including comprehensive care pre- and post-HT; however, perioperative HT care has previously occurred at the national paediatric centre or in adult centres. Internationally, perioperative HT care is highly protocol-driven and a majority of HT occurs in low volume centres. Establishing a low volume paediatric HT centre in New South Wales offers potential for quality HT care close to home. METHODS: Retrospective review of programme data for the first 12 months was undertaken. Patient selection was audited against the programme's intended initiation criteria. Longitudinal patient data on outcomes and complications were obtained from patient medical records. RESULTS: The programme's initial phase offered HT to children with non-congenital heart disease and no requirement for durable mechanical circulatory support. Eight patients met criteria for HT referral. Three underwent interstate transfer to the national paediatric centre. Five children (13-15 years, weight 36-85 kg) underwent HT in the new programme. Individual predicted 90-day mortality was 1.3-11.6%, with increased risk for recipients transplanted from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and with restrictive/hypertrophic cardiomyopathies. Survival at 90 days and for duration of follow-up is 100%. Observed programme benefits include mitigation of family dislocation and improved continuity of care within a family-centred programme. CONCLUSION: Audit of the first 12 months' activity of a second paediatric HT centre in Australia demonstrates adherence to proposed patient selection criteria and excellent 90-day patient outcomes. The programme demonstrates feasibility of care close to home, providing continuity for all patients including those requiring increased rehabilitation and psychosocial support post-transplantation.

Cheyne-stokes respiration in children with heart failure.

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine.

Pediatric cardiac waitlist mortality-Still too high.

Cardiac transplantation for children with end-stage cardiac disease with no other medical or surgical options is now standard. The number of children in need of cardiac transplant continues to exceed the number of donors considered "acceptable." Therefore, there is an urgent need to understand which recipients are in greatest need of transplant before becoming "too ill" and which "marginal" donors are acceptable in order to reduce waitlist mortality. This article reviewed primarily pediatric studies reported over the last 15 years on waitlist mortality around the world for the various subgroups of children awaiting heart transplant and discusses strategies to try to reduce the cardiac waitlist mortality.

Cognitive behavioural therapy plus standard care versus standard care for people with schizophrenia.

BACKGROUND: Cognitive behavioural therapy (CBT) is a psychosocial treatment that aims to re-mediate distressing emotional experiences or dysfunctional behaviour by changing the way in which a person interprets and evaluates the experience or cognates on its consequence and meaning. This approach helps to link the person's feelings and patterns of thinking which underpin distress. CBT is now recommended by the National Institute for Health and Care Excellence (NICE) as an add-on treatment for people with a diagnosis of schizophrenia. This review is also part of a family of Cochrane CBT reviews for people with schizophrenia. OBJECTIVES: To assess the effects of cognitive behavioural therapy added to standard care compared with standard care alone for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (up to March 6, 2017). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: We selected all randomised controlled clinical trials (RCTs) involving people diagnosed with schizophrenia or related disorders, which compared adding CBT to standard care with standard care given alone. Outcomes of interest included relapse, rehospitalisation, mental state, adverse events, social functioning, quality of life, and satisfaction with treatment.We included studies fulfilling the predefined inclusion criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We complied with the Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated relative risk (RR) and its 95% confidence interval (CI) for binary data and mean difference (MD) and its 95% confidence interval for continuous data. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: This review now includes 60 trials with 5,992 participants, all comparing CBT added to standard care with standard care alone. Results for the main outcomes of interest (all long term) showed no clear difference between CBT and standard care for relapse (RR 0.78, 95% CI 0.61 to 1.00; participants = 1538; studies = 13, low-quality evidence). Two trials reported global state improvement. More participants in the CBT groups showed clinically important improvement in global state (RR 0.57, 95% CI 0.39 to 0.84; participants = 82; studies = 2 , very low-quality evidence). Five trials reported mental state improvement. No differences in mental state improvement were observed (RR 0.81, 95% CI 0.65 to 1.02; participants = 501; studies = 5, very low-quality evidence). In terms of safety, adding CBT to standard care may reduce the risk of having an adverse event (RR 0.44, 95% CI 0.27 to 0.72; participants = 146; studies = 2, very low-quality evidence) but appears to have no effect on long-term social functioning (MD 0.56, 95% CI -2.64 to 3.76; participants = 295; studies = 2, very low-quality evidence, nor on long-term quality of life (MD -3.60, 95% CI -11.32 to 4.12; participants = 71; study = 1, very low-quality evidence). It also has no effect on long-term satisfaction with treatment (measured as 'leaving the study early') (RR 0.93, 95% CI 0.77 to 1.12; participants = 1945; studies = 19, moderate-quality evidence). AUTHORS' CONCLUSIONS: Relative to standard care alone, adding CBT to standard care appears to have no effect on long-term risk of relapse. A very small proportion of the available evidence indicated CBT plus standard care may improve long term global state and may reduce the risk of adverse events. Whether adding CBT to standard care leads to clinically important improvement in patients' long-term mental state, quality of life, and social function remains unclear. Satisfaction with care (measured as number of people leaving the study early) was no higher for participants receiving CBT compared to participants receiving standard care. It should be noted that although much research has been carried out in this area, the quality of evidence available is poor - mostly low or very low quality and we still cannot make firm conclusions until more high quality data are available.

Cognitive behavioural therapy plus standard care versus standard care plus other psychosocial treatments for people with schizophrenia.

BACKGROUND: Cognitive behavioural therapy (CBT) is a psychosocial treatment that aims to help individuals re-evaluate their appraisals of their experiences that can affect their level of distress and problematic behaviour. CBT is now recommended by the National Institute for Health and Care Excellence (NICE) as an add-on treatment for people with a diagnosis of schizophrenia. Other psychosocial therapies that are often less expensive are also available as an add-on treatment for people with schizophrenia. This review is also part of a family of Cochrane Reviews on CBT for people with schizophrenia. OBJECTIVES: To assess the effects of CBT compared with other psychosocial therapies as add-on treatments for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study Based Register of Trials (latest 6 March, 2017). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) involving people with schizophrenia who were randomly allocated to receive, in addition to their standard care, either CBT or any other psychosocial therapy. Outcomes of interest included relapse, global state, mental state, adverse events, social functioning, quality of life and satisfaction with treatment. We included trials meeting our inclusion criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We reliably screened references and selected trials. Review authors, working independently, assessed trials for methodological quality and extracted data from included studies. We analysed dichotomous data on an intention-to-treat basis and continuous data with 60% completion rate. Where possible, for binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CIs). We used a fixed-effect model for analyses unless there was unexplained high heterogeneity. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' table for our main outcomes of interest. MAIN RESULTS: The review now includes 36 trials with 3542 participants, comparing CBT with a range of other psychosocial therapies that we classified as either active (A) (n = 14) or non active (NA) (n = 14). Trials were often small and at high or unclear risk of bias. When CBT was compared with other psychosocial therapies, no difference in long-term relapse was observed (RR 1.05, 95% CI 0.85 to 1.29; participants = 375; studies = 5, low-quality evidence). Clinically important change in global state data were not available but data for rehospitalisation were reported. Results showed no clear difference in long term rehospitalisation (RR 0.96, 95% CI 0.82 to 1.14; participants = 943; studies = 8, low-quality evidence) nor in long term mental state (RR 0.82, 95% CI 0.67 to 1.01; participants = 249; studies = 4, low-quality evidence). No long-term differences were observed for death (RR 1.57, 95% CI 0.62 to 3.98; participants = 627; studies = 6, low-quality evidence). Only average endpoint scale scores were available for social functioning and quality of life. Social functioning scores were similar between groups (long term Social Functioning Scale (SFS): MD 8.80, 95% CI -4.07 to 21.67; participants = 65; studies = 1, very low-quality evidence), and quality of life scores were also similar (medium term Modular System for Quality of Life (MSQOL): MD -4.50, 95% CI -15.66 to 6.66; participants = 64; studies = 1, very low-quality evidence). There was a modest but clear difference favouring CBT for satisfaction with treatment - measured as leaving the study early (RR 0.86, 95% CI 0.75 to 0.99; participants = 2392; studies = 26, low quality evidence). AUTHORS' CONCLUSIONS: Evidence based on data from randomised controlled trials indicates there is no clear and convincing advantage for cognitive behavioural therapy over other - and sometimes much less sophisticated and expensive - psychosocial therapies for people with schizophrenia. It should be noted that although much research has been carried out in this area, the quality of evidence available is mostly low or of very low quality. Good quality research is needed before firm conclusions can be made.

Intensive case management for severe mental illness.

BACKGROUND: Intensive Case Management (ICM) is a community-based package of care aiming to provide long-term care for severely mentally ill people who do not require immediate admission. Intensive Case Management evolved from two original community models of care, Assertive Community Treatment (ACT) and Case Management (CM), where ICM emphasises the importance of small caseload (fewer than 20) and high-intensity input. OBJECTIVES: To assess the effects of ICM as a means of caring for severely mentally ill people in the community in comparison with non-ICM (caseload greater than 20) and with standard community care. We did not distinguish between models of ICM. In addition, to assess whether the effect of ICM on hospitalisation (mean number of days per month in hospital) is influenced by the intervention's fidelity to the ACT model and by the rate of hospital use in the setting where the trial was conducted (baseline level of hospital use). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (last update search 10 April 2015). SELECTION CRITERIA: All relevant randomised clinical trials focusing on people with severe mental illness, aged 18 to 65 years and treated in the community care setting, where ICM is compared to non-ICM or standard care. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, assessed quality, and extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses.We performed a random-effects meta-regression analysis to examine the association of the intervention's fidelity to the ACT model and the rate of hospital use in the setting where the trial was conducted with the treatment effect. We assessed overall quality for clinically important outcomes using the GRADE approach and investigated possible risk of bias within included trials. MAIN RESULTS: The 2016 update included two more studies (n = 196) and more publications with additional data for four already included studies. The updated review therefore includes 7524 participants from 40 randomised controlled trials (RCTs). We found data relevant to two comparisons: ICM versus standard care, and ICM versus non-ICM. The majority of studies had a high risk of selective reporting. No studies provided data for relapse or important improvement in mental state.1. ICM versus standard careWhen ICM was compared with standard care for the outcome service use, ICM slightly reduced the number of days in hospital per month (n = 3595, 24 RCTs, MD -0.86, 95% CI -1.37 to -0.34,low-quality evidence). Similarly, for the outcome global state, ICM reduced the number of people leaving the trial early (n = 1798, 13 RCTs, RR 0.68, 95% CI 0.58 to 0.79, low-quality evidence). For the outcome adverse events, the evidence showed that ICM may make little or no difference in reducing death by suicide (n = 1456, 9 RCTs, RR 0.68, 95% CI 0.31 to 1.51, low-quality evidence). In addition, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment due to very low-quality evidence (n = 1129, 4 RCTs, RR 0.70, 95% CI 0.49 to 1.0, very low-quality evidence).2. ICM versus non-ICMWhen ICM was compared with non-ICM for the outcome service use, there was moderate-quality evidence that ICM probably makes little or no difference in the average number of days in hospital per month (n = 2220, 21 RCTs, MD -0.08, 95% CI -0.37 to 0.21, moderate-quality evidence) or in the average number of admissions (n = 678, 1 RCT, MD -0.18, 95% CI -0.41 to 0.05, moderate-quality evidence) compared to non-ICM. Similarly, the results showed that ICM may reduce the number of participants leaving the intervention early (n = 1970, 7 RCTs, RR 0.70, 95% CI 0.52 to 0.95,low-quality evidence) and that ICM may make little or no difference in reducing death by suicide (n = 1152, 3 RCTs, RR 0.88, 95% CI 0.27 to 2.84, low-quality evidence). Finally, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment as compared to non-ICM (n = 73, 1 RCT, RR 1.46, 95% CI 0.45 to 4.74, very low-quality evidence).3. Fidelity to ACTWithin the meta-regression we found that i.) the more ICM is adherent to the ACT model, the better it is at decreasing time in hospital ('organisation fidelity' variable coefficient -0.36, 95% CI -0.66 to -0.07); and ii.) the higher the baseline hospital use in the population, the better ICM is at decreasing time in hospital ('baseline hospital use' variable coefficient -0.20, 95% CI -0.32 to -0.10). Combining both these variables within the model, 'organisation fidelity' is no longer significant, but the 'baseline hospital use' result still significantly influences time in hospital (regression coefficient -0.18, 95% CI -0.29 to -0.07, P = 0.0027). AUTHORS' CONCLUSIONS: Based on very low- to moderate-quality evidence, ICM is effective in ameliorating many outcomes relevant to people with severe mental illness. Compared to standard care, ICM may reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. Intensive Case Management is at least valuable to people with severe mental illnesses in the subgroup of those with a high level of hospitalisation (about four days per month in past two years). Intensive Case Management models with high fidelity to the original team organisation of ACT model were more effective at reducing time in hospital.However, it is unclear what overall gain ICM provides on top of a less formal non-ICM approach.We do not think that more trials comparing current ICM with standard care or non-ICM are justified, however we currently know of no review comparing non-ICM with standard care, and this should be undertaken.

Crisis intervention for people with severe mental illnesses.

BACKGROUND: A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis-intervention models of care were developed as a possible solution. OBJECTIVES: To review the effects of crisis-intervention models for anyone with serious mental illness experiencing an acute episode compared to the standard care they would normally receive. If possible, to compare the effects of mobile crisis teams visiting patients' homes with crisis units based in home-like residential houses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials. There is no language, time, document type, or publication status limitations for inclusion of records in the register. This search was undertaken in 1998 and then updated 2003, 2006, 2010 and September 29, 2014. SELECTION CRITERIA: We included all randomised controlled trials of crisis-intervention models versus standard care for people with severe mental illnesses that met our inclusion criteria. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: The update search September 2014 found no further new studies for inclusion, the number of studies included in this review remains eight with a total of 1144 participants. Our main outcomes of interest are hospital use, global state, mental state, quality of life, participant satisfaction and family burden. With the exception of mental state, it was not possible to pool data for these outcomes.Crisis intervention may reduce repeat admissions to hospital (excluding index admissions) at six months (1 RCT, n = 369, RR 0.75 CI 0.50 to 1.13, high quality evidence), but does appear to reduce family burden (at six months: 1 RCT, n = 120, RR 0.34 CI 0.20 to 0.59, low quality evidence), improve mental state (Brief Psychiatric Rating Scale (BPRS) three months: 2 RCTs, n = 248, MD -4.03 CI -8.18 to 0.12, low quality evidence), and improve global state (Global Assessment Scale (GAS) 20 months; 1 RCT, n = 142, MD 5.70, -0.26 to 11.66, moderate quality evidence). Participants in the crisis-intervention group were more satisfied with their care 20 months after crisis (Client Satisfaction Questionnaire (CSQ-8): 1 RCT, n = 137, MD 5.40 CI 3.91 to 6.89, moderate quality evidence). However, quality of life scores at six months were similar between treatment groups (Manchester Short Assessment of quality of life (MANSA); 1 RCT, n = 226, MD -1.50 CI -5.15 to 2.15, low quality evidence). Favourable results for crisis intervention were also found for leaving the study early and family satisfaction. No differences in death rates were found. Some studies suggested crisis intervention to be more cost-effective than hospital care but all numerical data were either skewed or unusable. We identified no data on staff satisfaction, carer input, complications with medication or number of relapses. AUTHORS' CONCLUSIONS: Care based on crisis-intervention principles, with or without an ongoing homecare package, appears to be a viable and acceptable way of treating people with serious mental illnesses. However only eight small studies with unclear blinding, reporting and attrition bias could be included and evidence for the main outcomes of interest is low to moderate quality. If this approach is to be widely implemented it would seem that more evaluative studies are still needed.

Iron deficiency and anemia in pediatric dilated cardiomyopathy are associated with clinical, biochemical, and hematological markers of severe disease and adverse outcomes.

BACKGROUND: There is limited evidence regarding the prevalence and impact of iron deficiency (ID) in children with dilated cardiomyopathy (DCM). METHODS: Retrospective single-center review of all children between 2010 and 2020 with a diagnosis of DCM and complete iron studies. ID was defined as ≥2 of ferritin <20 µg/liter, iron <9 µmol/liter, transferrin >3 g/liter, or transferrin saturation (TSat) <15%. Clinical and laboratory indices and freedom from a composite adverse event (CAE) of mechanical circulatory support (MCS), heart transplant, or death were compared between children with and without ID. RESULTS: Of 138 patients with DCM, 47 had available iron studies. Twenty-nine (62%) were iron deficient. Children with ID were more likely to be receiving inotropes (17, 59%, p = 0.005) or invasive/noninvasive ventilation (13, 45%, p = 0.016) than those who were iron replete. They had a higher incidence of anemia (22, 76%, p = 0.004) and higher NT-proBNP (1,590 pmol/liter, IQR 456-3,447, p = 0.001). Children with ID had significantly less freedom from the CAE at 1-year (54% ± 10%), 2-years (45 ± 10), and 5-years (37% ± 11%) than those without (p = 0.011). ID and anemia were the only significant predictors of the CAE on univariate Cox regression. CONCLUSIONS: ID is highly prevalent in children with DCM. Iron studies are undermeasured in clinical practice, but ID is associated with severe heart failure (HF) and an increased risk of the CAE. The need for iron replacement therapy should be considered in children who present in HF with DCM.

Haloperidol versus placebo for schizophrenia.

BACKGROUND: Haloperidol was developed in the late 1950s for use in the field of anaesthesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. OBJECTIVES: To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared with placebo. SEARCH METHODS: Initially, we electronically searched the databases of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH. We also checked references of all identified studies for further trial citations and contacted the authors of trials and pharmaceutical companies for further information and archive material.For the 2012 update, on 15 May 2012, we searched the Cochrane Schizophrenia Group's Trials Register. SELECTION CRITERIA: We included all relevant randomised controlled trials comparing the use of haloperidol (any oral dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). Our main outcomes of interest were death, loss to follow-up, clinical and social response, relapse and severity of adverse effects. DATA COLLECTION AND ANALYSIS: We evaluated data independently and extracted, re-inspected and quality assessed the data. We analysed dichotomous data using risk ratio (RR) and calculated their 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD). We excluded continuous data if loss to follow-up was greater than 50% and inspected data for heterogeneity. We used a fixed-effect model for all analyses. For the 2012 update, we assessed risk of bias of included studies and used the GRADE approach to create a 'Summary of findings' table. MAIN RESULTS: Twenty-five trials randomising 4651 people are now included in this review. We chose seven main outcomes of interest for the 'Summary of findings' table. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (4 RCTs n = 472, RR 0.67 CI 0.56 to 0.80, moderate quality evidence). A further eight trials also found a difference favouring haloperidol across the six weeks to six months period (8 RCTs n = 307 RR 0.67 CI 0.58 to 0.78, moderate quality evidence). Relapse data from two trials favoured haloperidol at < 52 weeks but the evidence was very low quality (2 RCTs n = 70, RR 0.69 CI 0.55 to 0.86). Moderate quality evidence showed about half of those entering studies failed to complete the short trials (six weeks to six months), although, at up to six weeks, 16 studies found a difference that marginally favoured haloperidol (n = 1812, RR 0.87 CI 0.80 to 0.95). Adverse effect data does, nevertheless, support clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Moderate quality evidence indicates that haloperidol caused parkinsonism (5 RCTs n = 485, RR 5.48 CI 2.68 to 11.22), akathisia (6 RCTs n = 695, RR 3.66 CI 2.24 to 5.97, and acute dystonia (5 RCTs n = 471, RR 11.49 CI 3.23 to 10.85). Discharge from hospital was equivocal between groups (1 RCT n = 33, RR 0.85 CI 0.47 to 1.52, very low quality evidence). Data were not reported for death and patient satisfaction. AUTHORS' CONCLUSIONS: Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should be less favoured as a control drug for randomised trials of new antipsychotics.

Risk stratification in Wolff-Parkinson-White syndrome: the correlation between noninvasive and invasive testing in pediatric patients.

BACKGROUND: In Wolff-Parkinson-White (WPW) syndrome, rapid antegrade conduction of atrial tachyarrhythmias can result in ventricular fibrillation and sudden death. Antegrade conduction can be assessed through noninvasive testing or invasive electrophysiology study (EPS). We aimed to determine the correlation between noninvasive testing and EPS in a pediatric WPW population. METHODS: All WPW patients <21 years who underwent EPS over a 10-year period were identified. Noninvasive testing reviewed included electrocardiogram, Holter, and exercise stress test (EST). Patients were classified as low-risk if preexcitation was lost during any test. EPS data reviewed included antegrade conduction during atrial pacing and atrial fibrillation. Conduction through the accessory pathway (AP) to a cycle length ≤ 250 ms was considered rapid, otherwise patients were nonrapid. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of noninvasive testing to correctly identify nonrapid conduction was calculated. RESULTS: There were 135 EPS. Twenty-four patients (18%) were classified low-risk noninvasively. Two of the 24 (8%) had rapid conduction at baseline EPS. The sensitivity, specificity, PPV, and NPV of low-risk noninvasive testing to predict nonrapid conduction was 22%, 94%, 92%, and 31%, respectively. Sixteen of the 24 had low-risk EST and none had rapid conduction at baseline EPS. The specificity and PPV of low-risk EST were 100%. CONCLUSION: Loss of preexcitation during noninvasive testing had high specificity and PPV for nonrapid antegrade conduction during baseline EPS. Abrupt loss of preexcitation during EST was a highly reliable noninvasive marker of nonrapid AP conduction at baseline in our pediatric WPW patients.

Mortality in infants with cardiovascular malformations.

UNLABELLED: Cardiovascular malformations are an important cause of infant death and the major cause of death due to malformation. Our aims were to analyse and categorise all deaths in infants with cardiovascular malformations, and to analyse trends in mortality over time and influences on mortality. We obtained details of infant deaths and cardiovascular malformations from the population of one health region for 1987-2006. We categorised deaths by cause and by presence of additional chromosomal or genetic abnormalities or non-cardiac malformations. In 676,927 live births the total infant mortality was 4,402 (6.5 per 1,000). A total of 4,437 infants had cardiovascular malformations (6.6 per 1000) of whom 458 (10.3%) died before 1 year of age. Of this number, 151 (33%) deaths had non-cardiac causes, 128 (28%) were cardiac without surgery and 179 (39%) occurred from cardiac causes after surgery. Death was unrelated to the cardiovascular malformation in 57% of infants with an additional chromosomal or genetic abnormality, in 76% of infants with a major non-cardiac malformation and in 16% of infants with an isolated cardiovascular malformation. Terminations of pregnancies affected by cardiovascular malformations increased from 20 per 100,000 registered births in the first 5 years to 78 per 100,000 in the last 5 years. A total of 2,067 infants (47%) underwent surgery and of these 216 (10%) died before 1 year of age. CONCLUSIONS: A total of 10.4% of infants who died had a cardiovascular malformation and two-thirds of deaths were due to the malformation or its treatment. Mortality declined due to increasing termination of pregnancy and improved survival after operation.

Crisis intervention for people with severe mental illnesses.

BACKGROUND: A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis intervention models of care were developed as a possible solution. OBJECTIVES: To review the effects of crisis intervention models for anyone with serious mental illness experiencing an acute episode, compared with 'standard care'. SEARCH METHODS: We updated the 1998, 2003 and 2006 searches with a search of the Cochrane Schizophrenia Group's Register of trials (2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE, and PsycINFO. SELECTION CRITERIA: We included all randomised controlled trials of crisis intervention models versus standard care for people with severe mental illnesses. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early from a trial had no improvement. MAIN RESULTS: Three new studies have been found since the last review in 2006 to add to the five studies already included in this review. None of the previously included studies investigated crisis intervention alone; all used a form of home care for acutely ill people, which included elements of crisis intervention. However, one of the new studies focuses purely on crisis intervention as provided by Crisis Resolution Home Teams within the UK; the two other new studies investigated crisis houses i.e. residential alternatives to hospitalisation providing home-like environments.Crisis intervention appears to reduce repeat admissions to hospital after the initial 'index' crises investigated in the included studies, this was particularly so for mobile crisis teams supporting patients in their own homes.Crisis intervention reduces the number of people leaving the study early, reduces family burden, is a more satisfactory form of care for both patients and families and at three months after crisis, mental state is superior to standard care. We found no differences in death outcomes. Some studies found crisis interventions to be more cost effective than hospital care but all numerical data were either skewed or unusable. No data on staff satisfaction, carer input, complications with medication or number of relapses were available. AUTHORS' CONCLUSIONS: Care based on crisis intervention principles, with or without an ongoing home care package, appears to be a viable and acceptable way of treating people with serious mental illnesses. If this approach is to be widely implemented it would seem that more evaluative studies are still needed.

Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia.

BACKGROUND: Cognitive behavioural therapy (CBT) is now a recommended treatment for people with schizophrenia. This approach helps to link the person's distress and problem behaviours to underlying patterns of thinking. OBJECTIVES: To review the effects of CBT for people with schizophrenia when compared with other psychological therapies. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (March 2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected all references of the selected articles for further relevant trials, and, where appropriate, contacted authors. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) of CBT for people with schizophrenia-like illnesses. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and assessed for methodological quality. Two review authors, working independently, extracted data. We analysed dichotomous data on an intention-to-treat basis and continuous data with 65% completion rate are presented. Where possible, for dichotomous outcomes, we estimated a risk ratio (RR) with the 95% confidence interval (CI) along with the number needed to treat/harm. MAIN RESULTS: Thirty papers described 20 trials. Trials were often small and of limited quality. When CBT was compared with other psychosocial therapies, no difference was found for outcomes relevant to adverse effect/events (2 RCTs, n = 202, RR death 0.57 CI 0.12 to 2.60). Relapse was not reduced over any time period (5 RCTs, n = 183, RR long-term 0.91 CI 0.63 to 1.32) nor was rehospitalisation (5 RCTs, n = 294, RR in longer term 0.86 CI 0.62 to 1.21). Various global mental state measures failed to show difference (4 RCTs, n = 244, RR no important change in mental state 0.84 CI 0.64 to 1.09). More specific measures of mental state failed to show differential effects on positive or negative symptoms of schizophrenia but there may be some longer term effect for affective symptoms (2 RCTs, n = 105, mean difference (MD) Beck Depression Inventory (BDI) -6.21 CI -10.81 to -1.61). Few trials report on social functioning or quality of life. Findings do not convincingly favour either of the interventions (2 RCTs, n = 103, MD Social Functioning Scale (SFS) 1.32 CI -4.90 to 7.54; n = 37, MD EuroQOL -1.86 CI -19.20 to 15.48). For the outcome of leaving the study early, we found no significant advantage when CBT was compared with either non-active control therapies (4 RCTs, n = 433, RR 0.88 CI 0.63 to 1.23) or active therapies (6 RCTs, n = 339, RR 0.75 CI 0.40 to 1.43) AUTHORS' CONCLUSIONS: Trial-based evidence suggests no clear and convincing advantage for cognitive behavioural therapy over other - and sometime much less sophisticated - therapies for people with schizophrenia.

Donor-specific HLA antibodies in paediatric cardiac transplant recipients are associated with poor graft survival.

There is increasing evidence that DSA are associated with poor graft survival, although there are little data in children. We aimed to describe the incidence of DSA in this group and to determine correlation with graft survival. HLA antibodies were analysed in 59 paediatric cardiac transplant recipients. Mean age 10.4 (0.7-18.5) yr, mean time post-transplant 5.1 (0.3-17.3) yr. Antibody detection/identification was performed on the Luminex platform with subsequent identification using Lifescreen Identification kits/One-Lambda Single antigen kits. Forty patients (69%) had no HLA antibodies. DSA were found in four (7%). One had transient Class I antibodies and normal cardiac function. The other three had persistent Class II antibodies (two subsequently required re-transplantation, the third had cardiac failure due to CAV). Non-DSA were found in 15 (25%), all with normal graft function and without rejection. There was no difference in function or CAV prevalence between those with non-DSA and those without antibodies. HLA DSA is uncommon in paediatric cardiac allograft recipients but, if persistent, suggests poorer prognosis. In our series, antibodies to HLA class II on donor tissue were associated with increased graft loss. Routine screening and regular testing are recommended.

Prognostic significance of recurrent grade 1B rejection in the first year after pediatric cardiac transplantation: a case for reinstatement of the 1B rejection grade.

The 2005 ISHLT rejection grading system merged grades 1A, 1B, and 2 into a single grade (1R) assuming equivalent prognostic significance. We hypothesized that recurrent 1B ACR is associated with adverse outcomes. Data on all heart transplant recipients at our center from 1990 to 2007 were reviewed. Patients were excluded if they had more than one grade ≥ 3A/2R biopsy in the first six wk or any grade ≥ 3A/2R biopsies during the first year thereafter. Patients with ≥ 2 grade 1B biopsies from six wk to one yr were classified as "recurrent 1B." Outcomes were freedom from late (greater than one yr) ACR (grade ≥ 3A/2R), CAD, retransplantation/death, and a composite end-point. Sixty-two patients (53 non-recurrent 1B, nine recurrent 1B) met inclusion criteria. In univariate analyses, recurrent 1B status was associated with decreased freedom from late ACR (p < 0.001), CAD (p = 0.004), and the composite outcome (p < 0.001). There was no difference in freedom from retransplantation/death (p = 0.48). After controlling for demographic differences between the groups, recurrent 1B status was independently associated with late ACR (HR 5.90; p = 0.002) and the composite outcome (HR 4.52; p = 0.002). These data suggest that further study of the impact of removal of the 1B classification from the ISHLT grading scheme is warranted.

WITHDRAWN: Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia.

BACKGROUND: Cognitive behavioural therapy (CBT) is now a recommended treatment for people with schizophrenia. This approach helps to link the person's feelings and patterns of thinking which underpin distress. OBJECTIVES: To review the effects of CBT for people with schizophrenia when compared to other psychological therapies. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (March 2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected all references of the selected articles for further relevant trials, and, where appropriate, contacted authors. SELECTION CRITERIA: All relevant clinical randomised trials of cognitive behaviour therapy for people with schizophrenia-like illnesses. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and assessed for methodological quality. Two reviewers, working independently, extracted data. We analysed dichotomous data on an intention-to-treat basis and continuous data with 65% completion rate are presented. Where possible, for dichotomous outcomes, we estimated a relative risk (RR) with the 95% confidence interval along with the number needed to treat/harm. MAIN RESULTS: Twenty-nine papers described 20 trials. Trials were often small and of limited quality. When CBT was compared with other psychosocial therapies no difference was found for outcomes relevant to adverse effect/events (2 RCTs, n=202, RR death 0.57 CI 0.12 to 2.60). Relapse was not reduced over any time period (5 RCTs, n=183, RR in long term 0.91 CI 0.63 to 1.32) nor was rehospitalisation (5 RCTs, n=294, RR in longer term 0.86 CI 0.62 to 1.21). Various global mental state measures failed to show difference (4 RCTs, n=244, RR no important change in mental state 0.84 CI 0.64 to 1.09). More specific measures of mental state failed to show differential effects on positive or negative symptoms of schizophrenia but there may be some longer term effect for affective symptoms (2 RCTs, n=105, MD BDI -6.21 CI -10.81 to -1.61). Few trials report on social functioning or quality of life. Findings do not convincingly favour either interventions (2 RCT, n=103, MD SFS 1.32 CI -4.90 to 7.54; n=37, MD EuroQOL -1.86 CI -19.20 to 15.48). For the outcome of leaving the study early we found no significant advantage when CBT was compared with either non-active control therapies (4 RCTs, n=433, RR 0.88 CI 0.63 to 1.23) or active therapies (6 RCTs, n=339, RR 0.75 CI 0.40 to 1.43) AUTHORS' CONCLUSIONS: Trail-based evidence suggests no clear and convincing advantage for cognitive behavioural therapy over other and sometime much less sophisticated therapies for people with schizophrenia.

Intensive case management for severe mental illness.

BACKGROUND: Intensive Case Management (ICM) is a community based package of care, aiming to provide long term care for severely mentally ill people who do not require immediate admission. ICM evolved from two original community models of care, Assertive Community Treatment (ACT) and Case Management (CM), where ICM emphasises the importance of small caseload (less than 20) and high intensity input. OBJECTIVES: To assess the effects of Intensive Case Management (caseload <20) in comparison with non-Intensive Case Management (caseload > 20) and with standard community care in people with severe mental illness. To evaluate whether the effect of ICM on hospitalisation depends on its fidelity to the ACT model and on the setting. SEARCH STRATEGY: For the current update of this review we searched the Cochrane Schizophrenia Group Trials Register (February 2009), which is compiled by systematic searches of major databases, hand searches and conference proceedings. SELECTION CRITERIA: All relevant randomised clinical trials focusing on people with severe mental illness, aged 18 to 65 years and treated in the community-care setting, where Intensive Case Management, non-Intensive Case Management or standard care were compared. Outcomes such as service use, adverse effects, global state, social functioning, mental state, behaviour, quality of life, satisfaction and costs were sought. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes we calculated relative risk (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data we estimated mean difference (MD) between groups and its 95% confidence interval (CI). We employed a random-effects model for analyses.We performed a random-effects meta-regression analysis to examine the association of the intervention's fidelity to the ACT model and the rate of hospital use in the setting where the trial was conducted with the treatment effect. MAIN RESULTS: We included 38 trials (7328 participants) in this review. The trials provided data for two comparisons: 1. ICM versus standard care, 2. ICM versus non-ICM.1. ICM versus standard care Twenty-four trials provided data on length of hospitalisation, and results favoured Intensive Case Management (n=3595, 24 RCTs, MD -0.86 CI -1.37 to -0.34). There was a high level of heterogeneity, but this significance still remained when the outlier studies were excluded from the analysis (n=3143, 20 RCTs, MD -0.62 CI -1.00 to -0.23). Nine studies found participants in the ICM group were less likely to be lost to psychiatric services (n=1633, 9 RCTs, RR 0.43 CI 0.30 to 0.61, I²=49%, p=0.05).One global state scale did show an Improvement in global state for those receiving ICM, the GAF scale (n=818, 5 RCTs, MD 3.41 CI 1.66 to 5.16). Results for mental state as measured through various rating scales, however, were equivocal, with no compelling evidence that ICM was really any better than standard care in improving mental state. No differences in mortality between ICM and standard care groups occurred, either due to 'all causes' (n=1456, 9 RCTs, RR 0.84 CI 0.48 to 1.47) or to 'suicide' (n=1456, 9 RCTs, RR 0.68 CI 0.31 to 1.51).Social functioning results varied, no differences were found in terms of contact with the legal system and with employment status, whereas significant improvement in accommodation status was found, as was the incidence of not living independently, which was lower in the ICM group (n=1185, 4 RCTs, RR 0.65 CI 0.49 to 0.88).Quality of life data found no significant difference between groups, but data were weak. CSQ scores showed a greater participant satisfaction in the ICM group (n=423, 2 RCTs, MD 3.23 CI 2.31 to 4.14).2. ICM versus non-ICM The included studies failed to show a significant advantage of ICM in reducing the average length of hospitalisation (n=2220, 21 RCTs, MD -0.08 CI -0.37 to 0.21). They did find ICM to be more advantageous than non-ICM in reducing rate of lost to follow-up (n=2195, 9 RCTs, RR 0.72 CI 0.52 to 0.99), although data showed a substantial level of heterogeneity (I²=59%, p=0.01). Overall, no significant differences were found in the effects of ICM compared to non-ICM for broad outcomes such as service use, mortality, social functioning, mental state, behaviour, quality of life, satisfaction and costs.3. Fidelity to ACT Within the meta-regression we found that i. the more ICM is adherent to the ACT model, the better it is at decreasing time in hospital ('organisation fidelity' variable coefficient -0.36 CI -0.66 to -0.07); and ii. the higher the baseline hospital use in the population, the better ICM is at decreasing time in hospital ('baseline hospital use' variable coefficient -0.20 CI -0.32 to -0.10). Combining both these variables within the model, 'organisation fidelity' is no longer significant, but 'baseline hospital use' result is still significantly influencing time in hospital (regression coefficient -0.18 CI -0.29 to -0.07, p=0.0027). AUTHORS' CONCLUSIONS: ICM was found effective in ameliorating many outcomes relevant to people with severe mental illnesses. Compared to standard care ICM was shown to reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. ICM is of value at least to people with severe mental illnesses who are in the sub-group of those with a high level of hospitalisation (about 4 days/month in past 2 years) and the intervention should be performed close to the original model.It is not clear, however, what gain ICM provides on top of a less formal non-ICM approach.We do not think that more trials comparing current ICM with standard care or non-ICM are justified, but currently we know of no review comparing non-ICM with standard care and this should be undertaken.

Successful medical treatment of bioprosthetic pulmonary valve endocarditis caused by methicillin-resistant Staphylococcus aureus.

The mortality risk of prosthetic valve endocarditis is known to be increased in cases in which staphylococci are the causative organisms. Previous recommendations have concentrated on early surgical management of this condition, but there are now reports that these infections can be treated medically, thus leaving prosthetic material in situ. We describe a case of methicillin-resistant Staphylococcus aureus endocarditis on a bovine pericardial pulmonary valve that responded to antibiotic therapy without the need for surgical intervention.

Immunosuppression therapy for pediatric heart transplantation.

OPINION STATEMENT: Outcomes following cardiac transplantation in childhood continue to improve. Advances in immunosuppressive therapy over the past two decades likely have contributed to this trend. The evolution in the management of immunosuppression in children has been based on clinical experience rather than on evidence-based medicine; indeed, there have been no pivotal randomized controlled trials of any form of immunosuppression in pediatric thoracic transplantation. Important trends in immunosuppressive therapy and transplant outcomes have been obtained from large transplant registries. Several trends have been identified since the last review of this topic in this journal. First, there is increased knowledge of the pharmacodynamics and pharmacokinetics of immunosuppressive drugs in children, with notable advances in the field of pharmacogenomics. These studies help explain individual variations in drug exposure, efficacy, and adverse events. They also help explain racial and ethnic variations in drug metabolism and efficacy. Second, there have been clear trends in the use of specific immunosuppressive medications. Use of induction therapy, especially polyclonal T cell-depleting antibody preparations, has increased significantly in recent years. The calcineurin inhibitor (CNI) tacrolimus is being used as the cornerstone of maintenance therapy in lieu of cyclosporine in more and more centers. Mounting evidence suggests that use of adjunctive agents (notably mycophenolate mofetil [MMF]) may improve outcomes, including survival, suggesting that monotherapy with CNIs is not the ideal maintenance therapy. Despite its increased cost, MMF has largely replaced azathioprine as the adjunctive agent of choice. Inhibitors of the mammalian target of rapamycin (i.e., sirolimus and everolimus) have not yet assumed a major place as adjunctive agents, as their safety and efficacy have not been well established in children. With the improvements in immunosuppressive therapy, the justification for routine corticosteroid use is far from clear, and many centers have shown excellent outcomes with complete steroid avoidance. Third, there is increasing interest in the importance of anti-HLA antibodies as important risk factors for adverse graft and patient outcomes. This is generating intense interest in treatments that target B cells and plasma cells. Finally, there is increasing realization that the "one size fits all" approach to immunosuppressive therapy is an obsolete concept and that the ultimate goal is to tailor immunosuppressive therapy to the needs of the individual patient. The development of reliable biomarkers of the patient's immune response to the allograft will be essential for optimal individualized immunosuppressive management.

ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.