Disentangling the effect of out-of-home care on child mental health.

BACKGROUND: Children in out-of-home care are consistently found to have poor mental health compared to children in the general population. However, UK research has so far failed to disentangle the impact of the care system on children's mental health outcomes from the effects of the adverse circumstances that led to their admission to care. OBJECTIVE: This research investigated the association between care placement and the presence of child mental health problems after controlling for children's pre-care experiences. It also identified factors associated with mental health problems among children in care. PARTICIPANTS AND SETTING: The sample comprised three groups of children involved with child welfare services due to maltreatment, including children in out-of-home care (n = 122), reunified children (n = 82) and those who had never been in care (n = 159). METHODS: The mental health of the children in the three groups was compared, using information collected from their parents/foster carers and social workers. RESULTS: The odds of a child in out-of-home care having a mental health problem were not significantly higher than those of a child who had never been in care (AOR = 1.24; p = 0.462). However, the odds of a child in out-of-home care having reactive attachment disorder (RAD) were significantly higher than those of a child who had never been in care (AOR=1.92; p = 0.032). CONCLUSIONS: These findings make an important contribution to international debates about whether placing children in care is beneficial or detrimental to their wellbeing, and highlight a range of inter-linking factors associated with the mental health of children in out-of-home care.

Mind-mindedness in parents of looked-after children.

The studies reported here aimed to test the proposal that mind-mindedness is a quality of personal relationships by assessing mind-mindedness in caregiver-child dyads in which the relationship has not spanned the child's life or in which the relationship has been judged dysfunctional. Studies 1 and 2 investigated differences in mind-mindedness between adoptive parents (ns = 89, 36) and biological parents from the general population (ns = 54, 114). Both studies found lower mind-mindedness in adoptive compared with biological parents. The results of Study 2 showed that this group difference was independent of parental mental health and could not fully be explained in terms of children's behavioral difficulties. Study 3 investigated differences in mind-mindedness in foster carers (n = 122), parents whose children had been the subject of a child protection plan (n = 172), and a community sample of biological parents (n = 128). The level of mind-mindedness in foster carers and parents who were involved with child protection services was identical and lower than that in the community sample; children's behavioral difficulties could not account for the difference between the 2 groups of biological parents. In all 3 studies, nonbiological carers' tendency to describe their children with reference to preadoption or placement experiences was negatively related to mind-mindedness. These findings are in line with mind-mindedness being a relational construct. (PsycINFO Database Record

Baseline cytokine profiling identifies novel risk factors for invasive fungal disease among haematology patients undergoing intensive chemotherapy or haematopoietic stem cell transplantation.

BACKGROUND: Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD. METHODS: We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment. Nine single nucleotide polymorphisms (TLR1, TLR2, TLR3, TLR4.1, TLR4.2, TLR6, CLEC7A, CARD9, and INFG) were investigated among transplant recipients and donors. FINDINGS: The incidence of IFD in this cohort was 16.9% (29/172). Median baseline serum concentrations of IL-15, IL-2R, CCL2, and MIP-1α were significantly higher whilst IL-4 was lower in patients with proven/probable IFD compared to those with no evidence of IFD. Baseline high IL-2R and CCL2 were associated with increased risk of IFD in the multivariate analysis (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.037], and hazard ratio 2.7 [95% CI 1.2-6.1; P = 0.016], respectively). However, these differences were not significant in follow up measurements. Similarly, no significant independent prognostic value was associated with baseline cytokine profile. INTERPRETATION: High baseline IL-2R and CCL2 concentrations were independent indicators of the risk of developing IFD and could be used to identify patients for enhanced prophylaxis and early antifungal therapy.

Triazole antifungals used for prophylaxis and treatment of invasive fungal disease in adult haematology patients: Trough serum concentrations in relation to outcome.

Triazole antifungal drugs are widely used for the prophylaxis and treatment of invasive fungal disease (IFD). Efficacy may depend on attaining minimum effective plasma concentrations. The aim of this study was to ascertain the proportion of samples in which the recommended concentrations were achieved in patients given these drugs in relation to outcome. In-patients prescribed standard doses of fluconazole, itraconazole solution, posaconazole suspension, or oral voriconazole for at least one week were studied. Pre-dose serum triazole concentrations were measured using validated methods. There were 359 samples from 90 patients. The median (range) number of samples per patient was 3 (1-13), and the median (range) fluconazole, itraconazole, posaconazole (prophylaxis), posaconazole (treatment), and voriconazole serum concentrations were 5.64 (0.11-18), 0.57 (0-5.3), 0.31 (0.02-2.5), 0.65 (0.02-2.5), and 0.95 (0.10-5.4) mg/l, respectively. The number of samples in which the recommended pre-dose concentrations were achieved was 98 (54%), 9 (20%), 2 (18%), and 29 (49%) for itraconazole, posaconazole (>0.7 mg/l prophylaxis), posaconazole (treatment), and voriconazole, respectively. No significant differences were detected in the median triazole trough concentrations between patients with proven/probable IFD compared to those with no evidence of IFD. However, itraconazole was not detected in 10 samples (7 patients). The small number of patients who achieved the recommended trough posaconazole concentrations may explain the high rate of break-through IFD observed in patients prescribed this drug. Except for fluconazole, the number of patients prescribed standard doses of triazoles who achieved recommended trough triazole concentrations was low. The prospective use of serum triazole measurements assay may have improved outcomes with itraconazole, posaconazole, and with voriconazole.

Pancreatic amylase is an environmental signal for regulation of biofilm formation and host interaction in Campylobacter jejuni.

Campylobacter jejuni is a commensal bacterium in the intestines of animals and birds and a major cause of food-borne gastroenteritis in humans worldwide. Here we show that exposure to pancreatic amylase leads to secretion of an α-dextran by C. jejuni and that a secreted protease, Cj0511, is required. Exposure of C. jejuni to pancreatic amylase promotes biofilm formation in vitro, increases interaction with human epithelial cell lines, increases virulence in the Galleria mellonella infection model, and promotes colonization of the chicken ileum. We also show that exposure to pancreatic amylase protects C. jejuni from stress conditions in vitro, suggesting that the induced α-dextran may be important during transmission between hosts. This is the first evidence that pancreatic amylase functions as an interkingdom signal in an enteric microorganism.

Reunifying abused or neglected children: Decision-making and outcomes.

Little is known about decision-making regarding the reunification of children in care, or about the consequences of these decisions for the children concerned. This study compared decision-making and outcomes for 149 maltreated children in seven English authorities (68 reunified, 81 who remained in care). Children were followed up six months after their return home or, for those who were not reunified, six months after the 'effective decision' that they should remain in care. They were followed up again four years (on average) after the return or effective decision. Data were extracted from case files at baseline and six month follow-up and were gathered from surveys of social workers and teachers at final follow-up. The two key predictors of reunification were assessments that parental problems had improved and that risks to the child were not unacceptably high. Two-thirds returned to improved family circumstances, sometimes due to a change in the household they returned to, but others were reunified despite persisting concerns. However 35% re-entered care within six months and 63% re-entered at some point during the four-year follow-up period, often due to recurring abuse or neglect. At final follow-up remaining in care was the strongest predictor of positive outcomes on a range of dimensions, even once children's characteristics and histories were taken into account. Outcomes were especially poor for neglected children who were reunified, irrespective of whether reunification was stable or unstable. Results show the potential of the care system to produce positive outcomes for maltreated children.

A comprehensive diagnostic approach using galactomannan, targeted ß-d-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients.

Invasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12-730) d. Baseline chest computerized tomography (CT) was performed pre-therapy. Twice-weekly surveillance with galactomannan (GM) was combined with targeted ß-d-glucan (BDG) testing on patients with possible IFD or who were GM-positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow-up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy-proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.

Baseline evaluation of serum markers of inflammation and their utility in clinical practice in paediatric liver transplant recipients.

BACKGROUND: Several biomarkers of penetrating infections vs. rejection in liver transplant (LT) have been suggested; however, baseline values in paediatric LT recipients have not been studied. AIM: We evaluated the baseline concentration of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) in a post-LT paediatric group. METHODS: We measured serum PCT, CRP and IL-6 in 58 consecutive paediatric LT recipients. Specimens were collected for group 1 (n=22) at day 1, group 2 (n=12) at day 7 post-LT and group 3 (n=24) at onset of febrile episode. Day 7 samples were obtained from patients who had no graft dysfunction or signs/symptoms of sepsis. RESULTS: Median values for PCT were: group 1 was 5.16 µg/L (95% CI, 2.18-21.13); group 2: 0.170 µg/L (95% CI, 0.15-0.36) and, group 3: 1.93 µg/L (95% CI, 1.36-2.66) for bacterial and fungal infection, 0.19 µg/L (95% CI, 0.10-0.48) for rejection, and 0.31 µg/L (95% CI, 0.15-0.44) for viral infection. The area under the ROC (AUROC) for PCT, CRP and IL-6 in bacterial infection vs. rejection was 1.0 (P<0.0001), 0.842 (95% CI 0.686-0.998; P<0.0001) and 0.739 (95% CI 0.559-0.919; P 0.0046), respectively. CONCLUSION: PCT levels were significantly higher in bacterial and fungal infection in comparison to other inflammatory markers. PCT proved to be the most specific parameter in differentiating bacterial infection from viral infection and allograft rejection.

Experience of microbiological screening of human hepatocytes for clinical transplantation.

Hepatocyte transplantation is being used in patients with liver-based metabolic disorders and acute liver failure. Hepatocytes are isolated from unused donor liver tissue under GMP conditions. Cells must be free of microbiological contamination to be safe for human use. The experience of microbiological screening during 72 hepatocyte isolation procedures at one center is reported. Samples were taken at different stages of the process and tested using a blood culture bottle system and Gram stain. Bacterial contamination was detected in 37.5% of the UW organ preservative solutions used to transport the liver tissue to the Cell Isolation Unit. After tissue processing the contamination was reduced to 7% overall in the final hepatocyte product, irrespective of the presence of initial contamination of the transport solution. The most common organisms recovered were coagulase-negative staphylococci, a skin commensal. A total of 41 preparations of fresh or cryopreserved hepatocytes were used for cell transplantation in children with liver-based metabolic disorders without any evidence of sepsis due to infusion of hepatocytes. In conclusion, the incidence of bacterial contamination of the final product was low, confirming the suitability of the organs used, hepatocyte isolation procedure, and the environmental conditions of the clean room.

Development and application of the active surveillance of pathogens microarray to monitor bacterial gene flux.

BACKGROUND: Human and animal health is constantly under threat by emerging pathogens that have recently acquired genetic determinants that enhance their survival, transmissibility and virulence. We describe the construction and development of an Active Surveillance of Pathogens (ASP) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes. RESULTS: The microarray consists of 4958 reporters from 151 bacterial species and include genes for the identification of individual bacterial species as well as mobile genetic elements (transposons, plasmid and phage), virulence genes and antibiotic resistance genes. The ASP microarray was validated with nineteen bacterial pathogens species, including Francisella tularensis, Clostridium difficile, Staphylococcus aureus, Enterococcus faecium and Stenotrophomonas maltophilia. The ASP microarray identified these bacteria, and provided information on potential antibiotic resistance (eg sufamethoxazole resistance and sulfonamide resistance) and virulence determinants including genes likely to be acquired by horizontal gene transfer (e.g. an alpha-haemolysin). CONCLUSION: The ASP microarray has potential in the clinic as a diagnostic tool, as a research tool for both known and emerging pathogens, and as an early warning system for pathogenic bacteria that have been recently modified either naturally or deliberately.

Nocardia nova aortitis after coronary artery bypass surgery.

Cardiac nocardiosis is a rare disease that is nearly always associated with cardiac operation. We report the case of a patient with a 10-month history of intermittent fevers after coronary artery bypass operation who presented with progressive shortness of breath and fever. He was found to have a large aortic aneurysm secondary to Nocardia nova infection likely transmitted during his original bypass operation. This is the first reported case of Nocardia aortitis after coronary bypass operation and serves to alert physicians of this rare but serious postoperative complication.

Toxoplasmosis following alemtuzumab based allogeneic haematopoietic stem cell transplantation.

Alemtuzumab is a humanised monoclonal antibody against CD52 used as an immunosuppressive agent in allogeneic HSCT. Regimens including alemtuzumab for allogeneic haematopoietic stem cell transplant (HSCT) conditioning have been associated with an increased incidence of viral complications. Patients with prior toxoplasma exposure undergoing alemtuzumab containing HSCT could therefore be expected to be at a higher risk of toxoplasma reactivation. We conducted a retrospective review of 220 alemtuzumab based allogeneic HSCT performed over a 4 year period, of which 202 were reduced intensity conditioning (RIC) HSCT. A total of 67 patients (30%) in whom the pre-transplant recipient toxoplasma IgG test was positive were classified as high-risk for toxoplasma infection. All patients started trimethoprim/sulfamethoxazole prophylaxis following HSCT when the neutrophil count was > or = 1x10(9)/l. Two high-risk patients developed toxoplasma invasive disease with cerebral involvement at 2 and 4 months post-transplantation respectively. The incidence of toxoplasma disease in the entire cohort and amongst high-risk patients was 0.9% and 3.0% respectively. Despite in vivo T-cell depletion with alemtuzumab, the incidence of toxoplasma disease in our cohort was comparable with previously reported T-cell replete HSCT studies.

Immunization issues before and after solid organ transplantation in children.

Solid-organ transplant recipients are at risk from various infectious diseases, many of which can be prevented by immunizations that could reduce morbidity and mortality. However, it is not uncommon for children requiring transplantation to have received inadequate or no immunizations pre-transplant. Every effort should be made to immunize transplant candidates early in the course of their disease according to recommended schedules prior to transplantation. It is also important to immunize their household contacts and healthcare workers. In this review, we summarize the major immunization issues for children undergoing transplantation, the data currently available on immunization safety and efficacy, and suggest immunization practices to reduce vaccine-preventable disease. There is a real need for a standardized approach to the administration and evaluation of immunizations in this group of patients.

Risk factors for fungal infection in paediatric liver transplant recipients.

Fungal infection (FI) is a major and potentially fatal complication in liver transplantation (LT). Published experience of FI in paediatric LT is limited. We therefore reviewed case records of 79 children, aged between 0.16 and 16 yr, who underwent LT between 1997 and 1998 to document the incidence of, and identify risk factors for, FI. Sixty-eight pre-, peri- and post-LT variables were assessed in relation to FI by univariate and multivariate analyses. The major indications for LT were biliary atresia in 26 (33%) patients, fulminant hepatic failure in 16 (20%) and intrahepatic cholestasis in 11 (14%); eight patients required re-LT. Thirty-two (40.5%) children developed a FI within 1 yr of LT. The median time to FI was 42 days (range 1-342 days). Candida spp. caused 29 (90.7%) FIs; 21 (66%) of these were Candida albicans. Although FI was associated with increased mortality, most patients responded well to antifungal treatment. The variables independently associated with FI were pre-LT fungal colonization and pyrexia and, post-LT, bacterial infection, Epstein-Barr virus (EBV) infection and tacrolimus administration. Identifying risk factors for FI should contribute to the development of strategies for prophylaxis or preemptive therapy.

Hepatocyte transplantation for inherited factor VII deficiency.

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.