Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis

Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF). Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥5 days of treatment, only 4 patients had average plasma concentrations of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml; P = 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml; P = 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P = 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r² = 0.95, P < 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population.     

Cognitive profiles of neurofibromatosis type 1 patients with minor brain malformations

Neurofibromatosis type 1 is a genetic condition associated with increased risk of abnormal brain development. The relationship between a specific type of brain malformation and a distinct cognitive sign/deficiency remains unknown. This study investigated the frequency of brain malformations in children with neurofibromatosis type 1, and the impact of those brain malformations on cognitive performance. A retrospective examination was performed of cranial magnetic resonance imaging and clinical records in 604 neurofibromatosis type 1 patients. Eighteen patients with brain malformations and intellectual evaluations were available and compared to a subset of neurofibromatosis type 1 patients (n = 20) without brain malformations. The most common brain malformations included hypothalamic hamartomas and Chiari I malformation. More complex migration disorders were also observed. Comparisons of cognitive profiles between groups revealed differences in patients with hamartomas compared with those manifesting Chiari I malformations or control subjects. As a group, those with hamartomas demonstrated below-average global intellect, whereas patients with Chiari I or no malformations performed in the average range. Disorders in cell organization, expressed as brain malformations (hamartomas or more complex defects), may comprise part of the expression of organizational and developmental defects in patients with neurofibromatosis type 1 and possibly other rat sarcoma gene-mitogen activated protein kinase pathway disorders.     

Family Social Support Modifies the Relationships Between Childhood Maltreatment Severity,Economic Adversity and Postpartum Depressive Symptoms

Objectives

This study examines the main and moderating effects of childhood abuse or neglect severity, income, and family social support on the presence of postpartum depressive symptoms (PDS).

Methods

Participants included 183 postpartum mothers who endorsed a history of childhood maltreatment (CM) and enrolled in a longitudinal study of mother and child outcomes. Participants completed questionnaires to assess CM severity, associated societal and maternal characteristics, and depressive symptom severity.

Results

The results confirm previously identified links between CM severity and PDS. Further, hierarchical linear regression analyses indicate the interaction of household income and interpersonal support from the family attenuates the relationship between CM severity and PDS. The final model accounted for 29% of the variance of PDS scores, a large effect size.

Conclusions

This study is the first to demonstrate interrelationships between income and social support on resilience to postpartum psychopathology in childhood trauma-surviving women. Social support appeared to protect against PDS for all mothers in this study while income only conferred a protective effect when accompanied by family support. For clinicians, this implies the need to focus on improving family and other relationships, especially for at-risk mothers.

     

Viral infections in newborns through exchange transfusion

Preprocedure sera of thirty one neonates requiring exchange transfusion were tested for serological markers of HBV, HCV, CMV, HIV and LFT. All the babies were investigated for these parameters one week and two months after transfusion to evaluate the risk of transmission of viral infection. Serological markers for these viral infections were also studied in the mothers and donors’ blood to establish the route of infection. Donors’ blood used for transfusion was pretested for HBsAg, VDRL and anti-HIV. HBsAg was detected one week post exchange in one baby and two months post exchange in two babies. Exchange transfusion was implicated in two of them, where one donor had HBsAg and the other anti-HBc. Vertical transmission accounted for the remaining one. Out of these HbsAg positive cases, one showed evidence of recently acquired CMV infection. Vertical transmission of anti-HCV was observed in one case. None of the neonates, mothers and donors were positive for anti-HIV. In view of probable serious consequences of HBV and HCV infections, blood used for exchange transfusion ought to be screened for anti-HBc and anti-HCV, besides routine HBsAg, VDRL and anti-HIV screening.     

Developmental Dysplasia of Hip and Post-natal Positioning: Role of Swaddling and Baby-Wearing

IntroductionTraditional swaddling, which implies restrictive immobilisation of the infant’s lower limbs with the hips in forced extension and adduction, has been shown to be a risk factor for Developmental Dysplasia of Hip (DDH).MethodsWe reviewed the literature regarding the correlation between DDH and post-natal positioning by swaddling and baby-wearing, to draw awareness of healthcare professionals towards an important risk factor for DDH that has often been overlooked.ResultsThere is overwhelming evidence in the literature, by both experimental and clinical studies, that proves the close association between improper post-natal positioning of the baby’s hips in extension-adduction and an increased incidence of DDH. On the other hand, “hip safe” swaddling which allows unrestricted flexion-abduction movements of the infants’ hips, and the use of baby-wearing devices which keep the lower limbs in an attitude of hip flexion-abduction and knee flexion, is optimal for hip development. Populations which practice these “hip-safe” techniques of infant immobilisation have a lower incidence of DDH as compared to those which practice restrictive immobilisation. Furthermore, populations which have adopted “hip-safe” positioning have demonstrated a significant decrease in the incidence of DDH. Understanding this association is vital, since this is a modifiable risk factor, rectification of which can decrease the incidence of DDH.ConclusionPolicy makers and governments must design educational campaigns tailored to their respective populations to increase awareness regarding the benefits of “hip-safe” techniques of infant positioning, since this simple intervention has the potential of decreasing the incidence of DDH.     

Short term analysis of healed post-tubercular kyphosis in younger children based on principles of congenital kyphosis

Background:

The patients with healed severe progressive tubercular kyphosis may develop late-onset paraplegia. A particular subgroup of these children (Type IB progression) may benefit from the management principles of congenital kyphosis. Self-correction may be observed by selective continued growth of anterior vertebral epiphyseal end-plates over the posterior fused mass. We report a series of cases with posterior fusion of progressive post-tubercular kyphosis with an aim to prevent further progression of kyphosis and to assess if any gradual self correction is seen in followup.

Materials and Methods:

Twelve children fulfilling inclusion criteria of clinicoradiological, hematological diagnosis of healed spine TB having no or <2 spine at risk signs having documented progression of kyphosis and neural deficit underwent posterior fusion in situ without instrumentation, using autogenous iliac crest grafts as well as allograft donor bone graft. They were followed up to maximum of 5 years.

Results:

All 12 children had a progressive increase in angle preoperatively. Mean followup was 3.6 years. Post surgery, 66% showed a clinical improvement and correction, 25% had static angle, and worsening in one patient. Thus, overall 91% have a favorable result.

Conclusion:

The mechanism of correction of deformity in presence of posterior fusion is continued growth of the anterior epiphyseal end plates and hence this leads to selective differential anterior column growth giving gradual correction of kyphosis. This avoids anterior, technically demanding and complex, internal gibbus surgeries. This procedure is simple, safe, and less morbid with good results, avoiding long term disability to the patients in selected group of patients.