Does age worsen EEG slowing and attention deficits in obstructive sleep apnea syndrome?

OBJECTIVE: The aim of this study was to determine whether EEG slowing is more pronounced in older than younger OSAS patients and to verify whether this cortical slowing is correlated to daytime performance, respiratory perturbation and sleep fragmentation. METHODS: Twelve young OSAS patients (mean age 38.2+/-2.0 y) and 13 older OSAS patients (mean age 62.2+/-1.9 y) along with 13 young controls (mean age 35.8+/-2.0 y) and 14 older controls (mean age 60.2+/-2.0 y) underwent a polysomnographic evaluation followed by a waking EEG recording. As a global index of cortical slowing, a ratio of slow-to-fast frequencies was calculated in all cortical regions. Daytime performance was assessed using the four choice reaction time test. RESULTS: Differences in waking EEG and in daytime performance were analyzed by ANOVAs with Group and Age as factors. Waking EEG did not yield a Group by Age interaction. OSAS patients had higher ratios across all regions than controls. Similarly, daytime performance revealed no Group by Age interaction. However, OSAS patients showed more lapses than controls and older subjects were slower than younger subjects. CONCLUSIONS: Our results indicate that age does not interact with OSAS to worsen the severity of cortical slowing, but age can add to the OSAS effect to worsen daytime performance deficits in OSAS patients. SIGNIFICANCE: The daytime performance deficits observed particularly in elderly OSAS patients warrant a careful clinical assessment of these patients to prevent accidents and injuries.     

A skin abscess model for teaching incision and drainage procedures

Background  

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.     

The Specific Endothelin A Receptor Antagonist ZD4054: Preclinical and Clinical Results

ContextZD4054 is a specific endothelin A (ET_A) receptor antagonist being investigated for the treatment of hormone-resistant prostate cancer (HRPC). ZD4054 binds specifically to the ET_A receptor, with no detectable activity at the ET_B receptor. In preclinical studies, ZD4054 inhibited endothelin (ET-1)-mediated changes in cellular invasiveness in vitro, and inhibited angiogenesis and growth of tumour xenografts in vivo. Consistent with its specific binding profile, ZD4054 inhibited ET_A-receptor-mediated antiapoptotic events while allowing ET_B-receptor-mediated proapoptotic signalling.Evidence acquisitionThe preclinical and clinical activity of ZD4054 is reviewed.Evidence synthesisIn the clinical setting, stable levels of circulating ET-1 following single ZD4054 doses up to 240 mg demonstrated the absence of ZD4054 activity at the ET_B receptor. ZD4054 is cleared principally via the urine, with a terminal elimination half-life of approximately 8–12 hours and with little accumulation after once-daily oral dosing.In a Phase 2 trial, patients with metastatic HRPC who were pain free or mildly symptomatic for pain were randomized to once-daily oral tablets of ZD4054 10 mg (n = 107), or 15 mg (n = 98), or matched placebo (n = 107). ZD4054 was generally well tolerated in this population, with an adverse effect profile consistent with its known pharmacological activity. The most common adverse effects were headache, peripheral oedema and nasal congestion. At the primary analysis there was no statistically significant difference in time to progression between the ZD4054-treated groups and placebo (hazard ratio [HR]: ZD4054 10 mg, 0.88 [80% CI 0.71, 1.09]; ZD4054 15 mg, 0.83 [0.66, 1.03]). However, a promising signal for prolonged overall survival was observed, which was sustained at a subsequent analysis (HR versus placebo: ZD4054 10 mg, 0.55 [80% CI 0.41, 0.73]; ZD4054 15 mg, 0.65 [0.49, 0.86]).ConclusionsThese results support the strategy of targeting the ET_A receptor in prostate cancer, and mandate further investigation of ZD4054 in Phase 3 clinical trials.     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

Lien précarité – durée et complexité des séjours hospitaliers en secteur de court séjour

BackgroundSeveral studies have shown that socioeconomic deprivation is associated with increased hospitalization lengths of stay (LOS) and costs. Yet, the French DRG-based information system (PMSI) does not take deprived situations into account. Hence, we aimed at extracting routinely available variables measuring deprivation from the Hospital Information System and at assessing their association with severity of illness and hospital LOS.MethodsWe performed record linkage between the PMSI database concerning stays of patients aged more than 16 years in the short-stay sector of Assistance publique–Hôpitaux de Paris in 2007 and an administrative database which provided the following deprivation measures: recipients of Couverture Médicale Universelle (basic or complementary health insurances adapted for underprivileged French citizens) or Aide Médicale d’État (health and medical emergency insurances adapted for underprivileged non French citizens living in France) and homeless patients. We compared length of stays showing a deprivation measure to others after adjustment on morbidity, age and sex.ResultsAmong 352,721 stays, the prevalence of the deprivation measures ranged from 0.71% for “homelessness” to 6.24% for complementary Couverture Médicale Universelle. Stays showing a deprivation measure had specific illnesses and had more frequently associated comorbidities or complications than others. After adjustment, deprivation measures were associated with significantly increased LOS (by 5% for Couverture Médicale Universelle to 48% for emergency Aide Médicale d’État.ConclusionRoutine extraction of deprivation measures from Hospital Information Systems is feasible. Age, sex and illness being equal, these deprivation measures were associated with more complicated cases and increased LOS. We recommend that case mix-based hospital prospective payment systems take socioeconomic deprivation into account.