Transitional care for patients with surgical pediatric hepatobiliary disease: Choledochal cysts and biliary atresia

Choledochal cysts (CDCs) and biliary atresia (BA) are rare pediatric hepatobiliary anomalies that require surgical intervention due to increased risk of malignancy and liver failure, respectively. The underlying disease and operative procedures place patients at risk for long‐term complications, which may continue to affect them into adulthood. Lack of a transitional care model in the health‐care system potentiates the challenges they will face following aging out of their pediatric providers' care. We sought to elucidate the long‐term complications and challenges patients with CDCs and BA face, review the current literature regarding transitioning care, and propose guidelines aiding adult providers in continued care and surveillance of these patients. A literature review was performed to assess short‐term and long‐term complications after surgery and the current standards for transitioning care in patients with a history of CDCs and BA. While transitional programs exist for patients with other gastrointestinal diseases, there are few that focus on CDCs or BA. Generally, authors encourage medical record transmission from pediatric to adult providers, ensuring accuracy of information and compliance with treatment plans. Patients with CDCs are at risk for developing biliary malignancies, cholangitis, and anastomotic strictures after resection. Patients with BA develop progressive liver failure, necessitating transplantation. There are no consensus guidelines regarding timing of follow up for these patients. Based on the best available evidence, we propose a schema for long‐term surveillance.     

Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress.

BACKGROUND: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers. DESIGN: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline. METHODS: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed. RESULTS: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample. CONCLUSION: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.     

Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.     

ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy.

OBJECTIVE: To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. METHODS: Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. RESULTS: Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with N1 latency in HIV patients and negatively with P3b amplitude in all subjects. CONCLUSIONS: These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART.     

Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

Compliance in amblyopia therapy: objective monitoring of occlusion.

AIM/BACKGROUND--This study aimed to determine the feasibility of objective compliance monitoring of amblyopia therapy in clinical research. Occlusion has been the mainstay of amblyopia therapy for over 250 years, yet it has never been subjected to rigorous evaluation. Treatment regimens range arbitrarily from a few minutes to most of the waking hours of the day. Compliance is problematic and as, hitherto, accurate objective monitoring has been impossible it is not known how much occlusion is required to effect an improvement in vision. METHODS--An occlusion dose monitor (ODM) has been developed. The ODM consists of a modified occlusion patch and a miniature battery driven datalogger which periodically monitors patch skin contact. The patch is a standard disposable item with two miniature electrocardiogram electrodes attached to its undersurface. The datalogger comprises a high speed static RAM and a clock driven address counter. Data are retrieved using an IBM PC/AT computer. Fifteen child amblyopes were randomly allocated unilateral occlusion of 1, 4, or 8 hours per day for 4 weeks. Owing to data loss, presumed because of accumulation and discharge of static electricity, an additional child was included in the 8 hour group. Outcome measures were objective (ODM) and subjective (diary) compliance with treatment, logMAR visual acuity, and contrast sensitivity. RESULTS--Objective monitoring of occlusion is technically feasible and clinically informative. CONCLUSION--Objective monitoring of occlusion has opened up new research opportunities which, it is hoped, will enable the dose-effect relation of occlusion therapy in the various types of amblyopia to be investigated objectively, and facilitate the design of effective therapeutic regimens.