Growth hormone (GH) exercises its growth effects by stimulating insulin-like growth factor I (IGF-I) synthesis in the liver (endocrine IGF-I) and by inducing chondrocyte differentiation/replication and local production of IGF-I (paracrine/autocrine IGF-I). Injectable recombinant human (rh)IGF-I (mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an insulin-sensitizing agent in severe insulin-resistant conditions. Although the insulin-sensitizing effect may benefit both type 1 and type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of IGF-I and include chronic liver disease, cystic fibrosis, wound healing, AIDS muscle wasting, burns, osteoporosis, Crohn’s disease, anorexia nervosa, Werner syndrome, X-linked severe combined immunodeficiency, Alzheimer’s disease, muscular dystrophy, amyotrophic lateral sclerosis, hearing loss prevention, spinal cord injury, cardiovascular protection, and prevention of retinopathy of prematurity. The most frequent side effect is hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve hyperplasia of lymphoid tissue, which may require tonsillectomy/adenoidectomy, accumulation of body fat, and coarsening of facies. The anti-apoptotic properties of IGF-I are implicated in cancer pathogenesis—a concern for long-term therapy. It is unlikely that mecasermin will be useful beyond the orphan indications of severe insulin resistance and GH insensitivity.

Topical oral sprays are frequently used to prevent and manage oropharyngeal inflammation and lesions. This study investigated the histopathologic changes noted in the oral mucosa of mice after topical application of 3 widely prescribed antibacterial products. The 25 animals were divided into 5 groups and treated for 10 days with 2 sprays daily, as follows: group 1—chlorhexidine gluconate 0.12% + benzydamine hydrochloride 0.15%; group 2—benzydamine 0.27 mg/0.18 mL x 30 mL; group 3—chlorhexidine 0.2%; group 4—fusafungine 1%; and group 5 (cohort)—physiologic serum. On day 10 after drug administration, biopsy specimens were taken from the oropharyngeal mucosa of the tongue, the cheek mucosa, and the tongue base; these were examined under a light microscope and were classified as normal or pathologic. All topical oral sprays produced some degree of histopathologic change, such as hyperplasia, fibrosis, low-grade dysplasia, congestion, or edema. The local irritant effects of topical oral sprays should be considered when treatment is selected for patients with oropharyngeal disorder.

A retrospective cohort study involving 29 Japanese patients with autoimmune hepatitis (AIH) was performed to clarify factors that predict the efficacy of prednisolone and the occurrence of various serious adverse effects. Independent predictors were identified by logistic analysis and with use of the Cox proportional hazard model. Responses to prednisolone were noted in 28 patients, who were classified into the complete remission group (52%) or the relapse group (48%). Multivariate analysis identified alanine aminotransferase, alkaline phosphatase, and immoglobulin G levels as independent predictors of relapse. The adverse effects most frequently observed were diabetes mellitus (37.9%), psychiatric/ neurologic symptoms (34.5%), and circulatory symptoms (34.5%). Predictive factors included lactate dehydrogenase, albumin, and fasting blood glucose levels for diabetes mellitus, alkaline phosphatase and C-reactive protein for psychiatric/neurologic symptoms, and autoimmune hepatitis score and lactate dehydrogenase for circulatory symptoms. Selection of an optimal treatment method for individual patients may be possible after the risks of relapse and adverse effects have been estimated.

Introduction

This study of UK patients examines clinical, healthrelated quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal®; Novartis, Switzerland) and Deferiprone (Ferriprox®; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated.

Methods

A naturalistic cohort study of 60 patients (betathalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO.

Results

Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately £19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs.

Conclusion

Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Serotonin (5-HT) receptors have been suggested to play key roles in psychosis, cognition, and mood via influence on neurotransmitters, synaptic integrity, and neural plasticity. Specifically, genetic evidence indicates that 5-HT_1A, 5-HT_2A, and 5-HT_2C receptor single-nucleotide polymorphisms (SNPs) are related to psychotic symptoms, cognitive disturbances, and treatment response in schizophrenia. Data from animal research suggest the role of 5-HT in cognition via its influence on dopaminergic, cholinergic, glutamatergic, and GABAergic function. This article provides up-to-date findings on the role of 5-HT receptors in endophenotypic variations in schizophrenia and the development of newer cognition-enhancing medications, based on basic science and clinical evidence. Imaging genetics studies on associations of polymorphisms of several 5-HT receptor subtypes with brain structure, function, and metabolism suggest a role for the prefrontal cortex and the parahippocampal gyrus in cognitive impairments of schizophrenia. Data from animal experiments to determine the effect of agonists/antagonists at 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors on behavioral performance in animal models of schizophrenia based on the glutamatergic hypothesis provide useful information. For this purpose, standard as well as novel cognitive tasks provide a measure of memory/information processing and social interaction. In order to scrutinize mixed evidence for the ability of 5-HT_1A agonists/antagonists to improve cognition, behavioral data in various paradigms from transgenic mice overexpressing 5-HT_1A receptors provide valuable insights. Clinical trials reporting the advantage of 5-HT_1A partial agonists add to efforts to shape pharmacologic perspectives concerning cognitive enhancement in schizophrenia by developing novel compounds acting on 5-HT receptors. Overall, these lines of evidence from translational research will facilitate the development of newer pharmacologic strategies for the treatment of cognitive disturbances of schizophrenia.

Despite advances in polymer and drug technology, the underlying stent platform remains a key determinant of clinical outcome. A clear understanding of stent design and the differences between various stent platforms are of increasing importance for the interventional cardiologist. Reduction in stent strut thickness has been associated with improved stent deliverability, improved procedural outcome, and lower rates of subsequent restenosis. Newer-generation 316L-SS stent designs have enabled reduced strut thickness while retaining radial strength and minimizing recoil, but with significant loss of radiopacity, leading to reduced visibility. Cobalt chromium alloys have enabled a reduction in stent strut thickness to around 80–90 mm while retaining modest radiopacity, but due to higher elastic properties, have been associated with greater stent recoil. Development of a novel 33% platinum chromium alloy with high radial strength and high radiopacity has enabled design of a new, thin-strut, flexible, easily visualized, and highly trackable stent platform, the use of which is further illustrated in several clinical case descriptions.

Ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) and neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (NPH) were compared for relief of pain in patients with acute otitis externa. Patients received 7 d of treatment with CIP/DEX twice daily or NPH 3 times daily. Ear pain was assessed by patients/caregivers twice daily and by the study investigator on days 3, 8, and 18 (4-point scale). Higher percentages of CIP/DEX-treated patients had relief of severe pain over time (P=.0013) and relief of significant pain (moderate or severe pain) over time (P=.0456), compared with NPH-treated patients. The percentage of CIP/DEX-treated patients with severe pain decreased rapidly within the first 12 h; this contrasted with an increase in pain among NPH-treated patients. CIP/DEX-treated patients had significantly less inflammation (P=.0043) and edema (P=.0148) than NPH-treated patients. Overall, these results support greater pain relief attained over the first 3 d in patients with acute otitis externa treated with CIP/DEX compared with NPH and a rapid reduction in severe pain after initiation of treatment.

The suboptimal outcomes of current chronic hepatitis B treatments have prompted the notion of combination therapy as a means of augmenting the therapeutic response. In this study, investigators compared lamivudine monotherapy versus its combination with conventional or pegylated interferon-α, pooling data from all pertinent randomized controlled studies into the meta-analysis. The studies were evaluated for methodologic quality and heterogeneity. Rates of sustained virologic and biochemical responses and of hepatitis B e antigen clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. Analysis yielded greater sustained virologic, biochemical, and seroconversion rates with the addition of conventional (odds ratio [OR]=4.5, 95% confidence interval [CI]=2.2–9.4,P}<.001; OR=2.1, 95% CI=1.3–3.2,P=.002; and OR=2.6, 95% CI=1.4–4.8,P=.001, respectively) and pegylated (OR=2.0, 95% CI=1.1–3.6,P=.02; OR=1.8, 95% CI=1.3–2.6,P}<.001; and OR=1.6, 95% CI=1.1–2.3,P=.03, respectively) interferon-α to lamivudine, with the former also yielding greater hepatitis B e antigen clearance rates (OR=2.6, 95% CI=1.3–5.2,P=.008). As previous studies suggested that pegylated interferon monotherapy and its combination with lamivudine were comparable, the use of this combination is not justified. In contrast, when conventional interferon-α is used, its combination with lamivudine should be considered.

A population-based, retrospective claims analysis was undertaken to explore the economic profile of a nebulized ipratropium and albuterol combination product (DuoNeb® [DN], DEY, L.P., Napa, Calif). This analysis was performed to review expenditures and resource utilization of patients with chronic obstructive pulmonary disease (COPD) who were taking DN or generic ipratropium and albuterol (dual single agents [DSA]). Cohort selection criteria applied to the PharMetrics managed care claims database yielded 1531 patients: 468 DN and 1063 DSA. Total per-member-per-month (PMPM) expenditures were $1840.36 for DN and $2046.73 DSA (Δ$206.37;P=.22). Emergency department (ED) costs were $36.67 for DN and $52.84 for DSA (Δ$16.17;P=.03). Differences in regression analysis adjusted least squares means between DSA and DN were $264.62 (P=.083) for total expenditures and $20.81 (P=.03) for ED costs. Resource utilization reflected expenditure observations; ED visits were 0.93 for DN and 1.33 for DSA (P < .001). Inpatient expenditures (DN $874.97, DSA $1105.80; Δ$230.83) represented the largest portion of total costs: 45% with DN and 54% with DSA. The DN cohort was associated with statistically fewer individuals who reported interruptions (0.78 vs 0.85;P=.003). The DN cohort did not appear to be more expensive than the DSA group, was associated with statistically lower ED expenditures, and included fewer individuals with therapy interruptions. Future analyses should include clinical data to better elucidate the full impact of DN on healthcare resources and compliance in the COPD population.