Mindfulness-Based Stress Reduction for Symptom Management in Older Individuals with HIV-Associated Neurocognitive Disorder.

The growing number of people aging with HIV represents a group vulnerable to the symptom burdens of HIV-associated neurocognitive disorder (HAND). Among younger groups, Mindfulness-Based Stress Reduction (MBSR) has been shown to help people living with HIV manage HIV-related and other life stress, and although there is some theoretical and empirical evidence that it may be effective among those with cognitive deficits, the approach has not been studied in older populations with HAND. Participants (n = 180) 55 years or older with HIV and cognitive impairment were randomly assigned to either an 8-week MBSR arm or a waitlist control. We assessed the impact of MBSR compared to a waitlist control on psychological outcomes [stress, anxiety, depression, and quality of life (QOL)] and cognitive metrics (e.g., speed of information processing, working memory, attention, impulsivity) measured at baseline, immediately post intervention (8 weeks) and one month later (16 weeks). Intent to treat analyses showed significant improvement in the MBSR group compared to control on symptoms of depression from baseline to 8 weeks, however, the difference was not sustained at 16 weeks. The MBSR group also showed improvement in perceived QOL from baseline to 16 weeks compared to the waitlist control group. Cognitive performance did not differ between the two treatment arms. MBSR shows promise as a tool to help alleviate the symptom burden of depression and low QOL in older individuals living with HAND and future work should address methods to better sustain the beneficial impact on depression and QOL.

Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic Nerve Pacing Catheter.

OBJECTIVES: Over 30% of critically ill patients on positive-pressure mechanical ventilation have difficulty weaning from the ventilator, many of whom acquire ventilator-induced diaphragm dysfunction. Temporary transvenous phrenic nerve pacing using a novel electrode-bearing catheter may provide a means to prevent diaphragm atrophy, to strengthen an atrophied diaphragm, and mitigate the harms of mechanical ventilation. We tested the initial safety, feasibility, and impact on ventilation of this novel approach. DESIGN: First-in-Humans case series. SETTING: Angiogram suite. PATIENTS: Twenty-four sedated, mechanically ventilated patients immediately prior to an elective atrial septal defect repair procedure. INTERVENTIONS: A 9.5-Fr central venous catheter with 19 embedded electrodes was placed via Seldinger technique into the left subclavian vein and superior vena cava and evaluated for up to 90 minutes. The electrode combinations determined to provide best transvenous stimulation of the right and left phrenic nerves were activated in synchrony with mechanically ventilated breaths. MEASUREMENTS AND MAIN RESULTS: One patient could not be tested for reasons unrelated to the device. In the 23 patients who underwent the full protocol, transvenous stimulation activated the diaphragm in 22 of 23 (96%) left phrenic capture attempts and 20 of 23 (87%) right phrenic capture attempts. In one subject, a congenital left-sided superior vena cava precluded right-sided capture. Significant reductions in ventilator pressure-time-product were achieved during stimulation assisted breaths in all 22 paced subjects (range, 9.9-48.6%; p < 0.001). There were no adverse events either immediately or at 2-week follow-up. CONCLUSIONS: In this First-in-Human series, diaphragm pacing with a temporary catheter was safe and effectively contributed to ventilation in conjunction with a mechanical ventilator.

Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation.

RATIONALE: Ventilator-induced diaphragm dysfunction is a significant contributor to weaning difficulty in ventilated critically ill patients. It has been hypothesized that electrically pacing the diaphragm during mechanical ventilation could reduce diaphragm dysfunction. OBJECTIVES: We tested a novel, central line catheter-based, transvenous phrenic nerve pacing therapy for protecting the diaphragm in sedated and ventilated pigs. METHODS: Eighteen Yorkshire pigs were studied. Six pigs were sedated and mechanically ventilated for 2.5 days with pacing on alternate breaths at intensities that reduced the ventilator pressure-time product by 20-30%. Six matched subjects were similarly sedated and ventilated but were not paced. Six pigs served as never-ventilated, never-paced control animals. MEASUREMENTS AND MAIN RESULTS: Cumulative duration of pacing therapy ranged from 19.7 to 35.7 hours. Diaphragm thickness assessed by ultrasound and normalized to initial value showed a significant decline in ventilated-not paced but not in ventilated-paced subjects (0.84 [interquartile range (IQR), 0.78-0.89] vs. 1.10 [IQR, 1.02-1.24]; P = 0.001). Compared with control animals (24.6 µm2/kg; IQR, 21.6-26.0), median myofiber cross-sectional areas normalized to weight and sarcomere length were significantly smaller in the ventilated-not paced (17.9 µm2/kg; IQR, 15.3-23.7; P = 0.005) but not in the ventilated-paced group (24.9 µm2/kg; IQR, 16.6-27.3; P = 0.351). After 60 hours of mechanical ventilation all six ventilated-paced subjects tolerated 8 minutes of intense phrenic stimulation, whereas three of six ventilated-not paced subjects did not (P = 0.055). There was a nonsignificant decrease in diaphragm tetanic force production over the experiment in the ventilated-paced and ventilated-not paced groups. CONCLUSIONS: These results suggest that early transvenous phrenic nerve pacing may mitigate ventilator-induced diaphragm dysfunction.

Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

Antidepressant drugs are usually administered for several weeks for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long-term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine to naïve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs) in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of 0.7 mg/kg fluoxetine on long-term potentiation (LTP) and long-term depression (LTD) in the CA1 hippocampal subfield. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining and immunohistochemical experiments revealed decreased AMPA-R Ca(2+) permeability in the stratum radiatum (s.r.) together with increased GluA2-containing Ca(2+) impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.