A single dose of noradrenergic/serotonergic reuptake inhibitors combined with an antimuscarinic does not improve obstructive sleep apnoea severity.

Previous trials have demonstrated that the combination of noradrenergic reuptake inhibitors with an antimuscarinic can substantially reduce the apnoea-hypopnoea index (AHI) and improve airway collapsibility in patients with obstructive sleep apnoea (OSA). However, some studies have shown that when administered individually, neither noradrenergic or serotonergic agents have been effective at alleviating OSA. This raises the possibility that serotonergic agents (like noradrenergic agents) may also need to be delivered in combination to be efficacious. Therefore, we investigated the effect of an antimuscarinic (oxybutynin) on OSA severity when administered with either duloxetine or milnacipran, two dual noradrenergic/serotonergic reuptake inhibiters. A randomized, double-blind, 4 way cross-over, placebo-controlled trial in ten OSA patients was performed. Patients received each drug condition separately across four overnight in-lab polysomnography (PSG) studies ~1-week apart. The primary outcome measure was the AHI. In addition, the four key OSA endotypes (collapsibility, muscle compensation, arousal threshold, loop gain) were measured non-invasively from the PSGs using validated techniques. There was no significant effect of either drug combinations on reducing the total AHI or improving any of the key OSA endotypes. However, duloxetine+oxybutynin did significantly increase the fraction of hypopnoeas to apnoeas (FHypopnoea ) compared to placebo (p = 0.02; d = 0.54). In addition, duloxetine+oxybutynin reduced time in REM sleep (p = 0.009; d = 1.03) which was positively associated with a reduction in the total AHI (R2  = 0.62; p = 0.02). Neither drug combination significantly improved OSA severity or modified the key OSA endotypes when administered as a single dose to unselected OSA patients.

Corneal hydrops secondary to undiagnosed keratoconus.

A 21-year old female presented to the emergency department with an abnormal appearance of her left eye after trivial trauma the previous day. A protruding, opaque appearing area was noted on the left cornea. The patient underwent visual acuity testing, fluorescein staining with slit lamp examination revealing a conical corneal protrusion with corneal stromal edema suggestive of corneal hydrops. Corneal hydrops is a rare complication of keratoconus and various corneal ectasias where aqueous humor can leak into the corneal stroma causing edema and protruding pockets of fluid. Treatment is based on treating the underlying keratoconus or corneal ectasia in addition to cycloplegics, topical corticosteroids, topical antibiotics, and topical hypertonic saline.

Characterization of a novel gyrovirus in human stool and chicken meat.

BACKGROUND: Sequence-independent amplification of clinical specimens can lead to the identification of novel pathogens. OBJECTIVES: To identify novel viruses in human stool specimens from patients with diarrhea and to investigate the ecology and clinical significance of such viruses. STUDY DESIGN: Nucleic acid extracted from stool specimens from patients with diarrhea with no known etiology were subjected to random PCR amplification and Roche/454 pyrosequencing. Novel viruses identified were genetically and epidemiologically characterized. RESULTS: Four gyroviruses, chicken anemia virus (CAV), human gyrovirus (HGV)/avian gyrovirus 2 (AGV2), gyrovirus 3 (GyV3) and a novel gyrovirus (tentatively designated as gyrovirus 4 (GyV4)) were identified in human stool specimens. GyV4, as well as CAV and AGV2/HGV were also detected in chicken skin and meat used for human consumption. CONCLUSIONS: A novel gyrovirus (GyV4) was identified in human stool and in chicken meat sold for human consumption. This virus was phylogenetically distinct from previously reported gyroviruses in chicken and humans (chicken anemia virus, human gyrovirus, avian gyrovirus 2 and recently reported gyrovirus 3). The epidemiology and pathogenesis of this virus in humans and in chicken needs to be further investigated.

Protracted withdrawal from cocaine self-administration flips the switch on 5-HT(1B) receptor modulation of cocaine abuse-related behaviors.

BACKGROUND: The role of serotonin-1B receptors (5-HT(1B)Rs) in modulating cocaine abuse-related behaviors has been controversial due to discrepancies between pharmacological and gene knockout approaches and opposite influences on cocaine self-administration versus cocaine-seeking behavior. We hypothesized that modulation of these behaviors via 5-HT(1B)Rs in the mesolimbic pathway may vary depending on the stage of the addiction cycle. METHODS: To test this hypothesis, we examined the effects of increasing 5-HT(1B)R production by microinfusing a viral vector expressing either green fluorescent protein and 5-HT(1B)R or green fluorescent protein alone into the medial nucleus accumbens shell of rats either during maintenance of cocaine self-administration (i.e., active drug use) or during protracted withdrawal. RESULTS: 5-HT(1B)R receptor gene transfer during maintenance shifted the dose-response curve for cocaine self-administration upward and to the left and increased breakpoints and cocaine intake on a progressive ratio schedule, consistent with enhanced reinforcing effects of cocaine. In contrast, following 21 days of forced abstinence, 5-HT(1B)R gene transfer attenuated breakpoints and cocaine intake on a progressive ratio schedule of reinforcement, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. CONCLUSIONS: This unique pattern of effects suggests that mesolimbic 5-HT(1B)Rs differentially modulate cocaine abuse-related behaviors, with a facilitative influence during periods of active drug use, in striking contrast to an inhibitory influence during protracted withdrawal. These findings suggest that targeting 5-HT(1B)Rs may lead to a novel treatment for cocaine dependence and that the therapeutic efficacy of these treatments may vary depending on the stage of the addiction cycle.

Telehome monitoring in patients with cardiac disease who are at high risk of readmission.

Patients with chronic conditions are heavy users of the health care system. There are opportunities for significant savings and improvements to patient care if patients can be maintained in their homes. A randomized control trial tested the impact of 3 months of telehome monitoring on hospital readmission, quality of life, and functional status in patients with heart failure or angina. The intervention consisted of video conferencing and phone line transmission of weight, blood pressure, and electrocardiograms. Telehome monitoring significantly reduced the number of hospital readmissions and days spent in the hospital for patients with angina and improved quality of life and functional status in patients with heart failure or angina. Patients found the technology easy to use and expressed high levels of satisfaction. Telehealth technologies are a viable means of providing home monitoring to patients with heart disease at high risk of hospital readmission to improve their self-care abilities.