Evaluation of drug interaction software to identify alerts for transplant medications

BACKGROUND: The ability of computerized physician order entry (CPOE) systems to identify clinically significant drug interactions is dependent upon the integrity of the drug information populating the software. A CPOE system with incomplete or inaccurate drug information will fail to identify clinically important drug interactions and, therefore, fail to reduce preventable adverse drug events (pADEs). OBJECTIVE: To evaluate, from the prescribers' perspective, the ability of a common drug interaction database to identify clinically important drug interactions involving drugs used in transplantation. METHODS: The clinical significance of drug interactions involving 5 transplant drugs was evaluated by an expert panel to determine whether alerts should be generated for physicians not involved in the transplant at the time of order entry. Drug interactions included in the analysis were generated from the expert panel, a common drug interaction database, and 2 standard drug interaction references. Responses on the clinical significance were used to calculate the sensitivity, specificity, and positive and negative predictive values for each severity setting of a common electronic drug interaction database. RESULTS: Overall, the database failed to identify approximately 70% of interactions considered significant by the expert panel. Of the alerts that were generated, >85% were considered clinically significant. The database was most deficient in identifying interactions resulting from additive toxicity. CONCLUSIONS: To expect a decrease in pADEs caused by drug interactions, the information used to populate CPOE systems must be validated. Establishing consistency and integrity of this information may be a future role for pharmacists.     

Autozygome maps dispensable DNA and reveals potential selective bias against nullizygosity

PurposeCopy number variants are an important source of human genome diversity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated.MethodsWe analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring.ResultsAnalysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping “dispensable” DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages.ConclusionsThe autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy individuals.Genet Med 2012:14(5):515–519     

Proximal realignment surgery for unilateral chronic patella dislocation in Morquio syndrome: a case report

Mucopolysaccharidosis IVA (MPS IVA: Morquio A syndrome) is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Patients with MPS IVA appear healthy at birth. Morquio-specific radiographic changes can be observed prior to clinical signs and symptoms. Patients are usually affected by a severe joint degeneration from the 2nd or 3rd decade. Hyperlaxity of the joints is prominent due to the excess of intermediate metabolites. We report a patient with inherited dwarfism, in which a proximal soft tissue realignment procedure was performed to treat chronic patellar dislocation.     

Treatment of Airway Complications Following Lung Transplantation

ObjectiveTo describe our experience in airway complications following lung transplantation and to suggest a management strategy using different interventional bronchoscopic techniques.MethodRetrospective analysis of all airway complications following lung transplantation from January 1999 to July 2007.ResultsDuring this period, 223 patients underwent lung transplantation, with a total of 345 airway anastomoses. In 70 (20.23%), there were complications requiring endoscopic intervention. A total of 631 procedures were carried out in 52 patients. Thirty-three patients presented a combination of bronchial stenosis and bronchomalacia, 18 patients had bronchial stenosis alone and 1 patient presented dehiscence of the anastomosis. In most cases, pneumatic balloon dilatation was effective, although temporarily, and ultimately 47 patients required endobronchial stent placement. The most common complication associated with the use of stents was granulation tissue formation, seen in 57.3% of patients. After stent placement, forced expiratory volume in one second (FEV₁) improved significantly.ConclusionAirway complications after lung transplantation are frequent. Balloon dilatation was effective in only a few patients with bronchial stenosis, requiring stent placement in most. Airway permeabilization after endobronchial stent placement improved FEV₁ in these patients. Based on our experience, we propose a management strategy for airway complications after lung transplantation.     

Isolated medial cuneiform fractures: report of two cases and review of the literature

Although fractures of the midfoot are common, cuneiform fractures are rarely seen. These fractures are frequently associated with other fractures of the midfoot such as Lisfranc fracture-dislocations. However, isolated cuneiform fractures are extremely rare, with few cases reported in the relevant literature. Herein, the authors report 2 cases of isolated medial cuneiform fractures. One of the patients was treated with headless screw fixation due to displacement in fracture configuration, and the other was treated conservatively. Fractures were united without any complication in both patients. In this report, the authors discuss the mechanism of injury, diagnostic challenges, and treatment options of isolated medial cuneiform fractures.     

Waiting for lung transplantation: quality of life, mood, caregiving strain and benefit, and social intimacy of spouses

BACKGROUND: The emotional and physical well-being of lung transplant patients is enhanced by the availability and stability of a primary caregiver. METHODS: We describe the quality of life (QOL), mood, caregiving strain and benefits, and social intimacy of 73 lung transplant caregivers who completed the QOL Inventory, SF-36 Health Survey, Profile of Mood States, Caregiver Strain Index, Caregiver Benefit Index, and Miller Social Intimacy Scale. RESULTS: Clinically low QOL was reported by 17.8-35.6% of spouses. Relative to a normative sample, spouses reported significantly lower physical (z = 4.01, p < 0.001) and emotional (z = 7.01, p < 0.001) QOL. Over half (56.2%) had clinically elevated caregiving strain. Heightened physical strain (80.8%), inconvenience (79.5%), feeling confined (72.6%), feeling upset that patient has changed so much (69.9%) contributed most to caregiver strain, while discovering inner strength (60.3%), support from others (53.4%), and realizing what is important in life (42.5%) were noted caregiving benefits. Higher caregiving strain was associated with more mood disturbance (r = 0.42, p < 0.001), lower emotional QOL (r = -0.39, p < 0.002), lower social intimacy (r = -0.37, p < 0.002), and longer disease duration (r = 0.55, p < 0.001). CONCLUSION: Spouses of patients awaiting lung transplantation may experience QOL deficits and high caregiver strain. Interventions to improve QOL and reduce caregiver strain are needed.     

Complexity and function of cytokine responses in experimental infection by Echinococcus granulosus

Cytokines are important in the regulation of the immune system and are secreted by a variety of cells in response to self and non-self stimuli. Communication within cells, in the same or distant anatomical sites, occurs via cytokines which determine the quality and intensity of inflammatory and adaptive immune responses. Infection by helminths is characterized by a dominant secretion of type-2 cytokines; IL-4, IL-5, IL-10 (among others), which down-regulates the induction and functions of type-1 cytokines. The molecular mechanisms involved in the polarization of type-2 responses and their biological significance in helminthic infections are unknown, and probably depends on each host-parasite system. Understanding these issues may contribute to immune therapy against parasitic infections. Here we summarize our data obtained in Echinococcus granulosus experimental infection regarding type-2 cytokine induction and its putative role in the host-parasite interaction. Results suggest that induction of cytokine responses at different stages of infection is complex and depends on several parameters. In addition, they support the hypothesis that early IL-10, secreted by B cells in response to non-proteic antigens, may favour parasite survival and the establishment of a polarized type-2 cytokine response.