Interim Safety Profile From the Feasibility Study of the BrainGate Neural Interface System.

BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.

Antibiotic exposure and room contamination among patients colonized with vancomycin-resistant enterococci.

OBJECTIVE: To determine whether total and antianaerobic antibiotic exposure increases the risk of room contamination among vancomycin-resistant enterococci (VRE)-colonized patients. DESIGN AND SETTING: A 14-month study in 2 intensive care units at an academic tertiary care hospital in Boston, Massachusetts. PATIENTS: All patients who acquired VRE or were VRE-colonized on admission and who had environmental cultures performed. METHODS: We performed weekly environmental cultures (2 sites per room) and considered a room to be contaminated if there was a VRE-positive environmental culture during the patient's stay. We determined risk factors for room contamination by use of the Cox proportional hazards model. RESULTS: Of 142 VRE-colonized patients, 35 (25%) had an associated VRE-positive environmental culture. Patients who contaminated their rooms were more likely to have diarrhea than those who did not contaminate their rooms (23 [66%] of 35 vs 41 [38%] of 107; P = .005) and more likely to have received antibiotics while VRE colonized (33 [94%] of 35 vs 86 [80%] of 107; P = .02). There was no significant difference in room contamination rates between patients exposed to antianaerobic regimens and patients exposed to nonantianaerobic regimens or between patients with and patients without diarrhea, but patients without any antibiotic exposure were unlikely to contaminate their rooms. Diarrhea and antibiotic use were strongly confounded; although two-thirds of room contamination occurred in rooms of patients with diarrhea, nearly all of these patients received antibiotics. In multivariable analysis, higher mean colonization pressure in the ICU increased the risk of room contamination (adjusted hazard ratio per 10% increase, 1.44 [95% confidence interval, 1.04-2.04]), whereas no antibiotic use during VRE colonization was protective (adjusted hazard ratio, 0.21 [95% confidence interval, 0.05-0.89]). CONCLUSIONS: Room contamination with VRE was associated with increased mean colonization pressure in the ICU and diarrhea in the VRE-colonized patient, whereas no use of any antibiotics during VRE colonization was protective.

Prior environmental contamination increases the risk of acquisition of vancomycin-resistant enterococci.

BACKGROUND: Patients colonized with vancomycin-resistant enterococci (VRE) frequently contaminate their environment, but the environmental role of VRE transmission remains controversial. METHODS: During a 14-month study in 2 intensive care units, weekly environmental and twice-weekly patient surveillance cultures were obtained. VRE acquisition was defined as a positive culture result >48 h after admission. To determine risk factors for VRE acquisition, Cox proportional hazards models using time-dependent covariates for colonization pressure and antibiotic exposure were examined. RESULTS: Of 1330 intensive care unit admissions, 638 patients were at risk for acquisition, and 50 patients (8%) acquired VRE. Factors associated with VRE acquisition included average colonization pressure (hazard ratio [HR], 1.4 per 10% increase; 95% confidence interval [CI], 1.2-1.8), mean number of antibiotics (HR, 1.7 per additional antibiotic; 95% CI, 1.2-2.5), leukemia (HR, 3.1; 95% CI, 1.2-7.8), a VRE-colonized prior room occupant (HR, 3.1; 95% CI, 1.6-5.8), any VRE-colonized room occupants within the previous 2 weeks (HR, 2.5; 95% CI, 1.3-4.8), and previous positive room culture results (HR, 3.4; 95% CI, 1.2-9.6). In separate multivariable analyses, a VRE-colonized prior room occupant (HR, 3.8; 95% CI, 2.0-7.4), any VRE-colonized room occupants within the previous 2 weeks (HR, 2.7; 95% CI, 1.4-5.3), and previous positive room culture results (HR, 4.4; 95% CI, 1.5-12.8) remained independent predictors of VRE acquisition, adjusted for colonization pressure and antibiotic exposure. CONCLUSIONS: We found that prior room contamination, whether measured via environmental cultures or prior room occupancy by VRE-colonized patients, was highly predictive of VRE acquisition. Increased attention to environmental disinfection is warranted.

The impact of gown-use requirement on hand hygiene compliance.

BACKGROUND: Hand hygiene compliance remains low, despite its effectiveness in preventing infections. Gowns are routinely used to reduce dissemination of organisms within hospitals. Use of gowns is time consuming and costly, and their effectiveness, compared with that of hand hygiene alone, is debated. Among the arguments supporting a gown-use requirement is the potential to boost awareness of infection control, leading to improved hand hygiene compliance. METHODS: Hand hygiene compliance was recorded in a 14-month crossover trial comparing compliance at 2 intensive care units during periods with and without a gown-use requirement. RESULTS: During 170 h of observation, 1619 hand hygiene opportunities were recorded. Compliance was 10% before care was given and 36% after care was given. Compliance with glove and gown use was 62% and 63%, respectively. After-care hand hygiene compliance for nurses, physicians, and therapists was 40%, 38%, and 22%, respectively. Compliance after patient contact, body fluid contact, and other in-room activity was 42%, 48%, and 22%, respectively. For periods with and without a gown-use requirement, overall after-care compliance (37% vs. 34%) and rates by personnel and activity type were similar. In the subgroup of patients on contact precautions, hand hygiene compliance during the period with a gown-use requirement versus the period without a gown-use requirement was 11% versus 10% (P=.85) before care was given and 45% versus 39% (P=.09) after care was given. In this subgroup, after adjustment for type of in-room activity, medical personnel, intensive care unit, and observer, the predicted after-care hand hygiene compliance during periods with and without a gown-use requirement was 48% versus 41% (P=.02). CONCLUSIONS: The hypothesis that a gown-use requirement might improve hand hygiene compliance in the intensive care unit could not be confirmed. In the subgroup of patients on contact precautions, improvement in hand hygiene compliance associated with the gown-use requirement was small and did not affect precare rates.

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.

The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection or receipt of a CMV-seropositive donor liver has been shown to be an independent predictor of bacteremia in orthotopic liver transplant (OLT) recipients. However, prevention of CMV infection through use of intense CMV prophylaxis has not been examined to assess the impact on bacteremia in liver transplant recipients. METHODS: We analyzed the impact of CMV prophylaxis on rates of bacteremia by examining 192 consecutive OLT recipients during a 2-year follow-up period. RESULTS: There were 29 episodes of bacteremia. Univariate analysis of risk factors for bacteremia showed that invasive fungal disease, initial anti-lymphocyte immunosuppression, treatment for rejection, and use of solumedrol were significantly associated with increased risk. Receipt of >or=14 days of ganciclovir prophylaxis (hazard ratio [HR], 0.40; 95% CI [confidence interval], 0.18-0.87; P=.02), end-to-end biliary anastomosis, and receipt of <10 units of red blood cells (RBCs) were significantly associated with a decreased risk. Three-variable analysis controlling for end-to-end anastomosis and use of <10 units of RBCs, showed that use of >or=14 days of ganciclovir was still associated with a reduced risk of bacteremia (HR, 0.44; 95% CI, 0.20-0.98; P=.0437). CONCLUSIONS: Among factors associated with bacteremia, use of prophylactic ganciclovir is independently associated with a significant reduction of bacteremia in OLT recipients.

Role of environmental contamination as a risk factor for acquisition of vancomycin-resistant enterococci in patients treated in a medical intensive care unit.

BACKGROUND: Colonization pressure, proximity to another case, exposure to a nurse who cares for another case, enteral feeding, and the use of sucralfate, vancomycin hydrochloride, cephalosporins, or antibiotics are among the defined risk factors for acquisition of vancomycin-resistant enterococci (VRE) in the intensive care unit (ICU) setting. However, the role of rooms with contaminated environmental surfaces has not been well delineated. METHODS: Retrospective case-control study conducted on patients admitted to the medical ICU (MICU) of a tertiary-care, university-affiliated medical center during a 9-month period. Patients who acquired VRE (cases) were matched with 2 randomly selected control subjects who did not acquire VRE and had been in the MICU for at least the same number of days. RESULTS: Thirty cases were matched with 60 appropriate controls. Cases were more likely to have been in the hospital for longer than 7 days before MICU admission (P =.009); to have occupied a specific room with persisting contaminated surfaces (P =.06); to have had a central venous catheter (P =.05); to have received vancomycin (P =.02), cephalosporins (P =.03), and quinolones (P =.006) before MICU admission; and to have received vancomycin (P =.02) and metronidazole sodium phosphate (P =.03) after MICU admission. Multivariate analysis showed that a hospital stay of longer than 1 week before MICU admission (P =.04), use of vancomycin before or after MICU admission (P =.03), use of quinolones before MICU admission (P =.03), and placement in a contaminated room (P =.02) were the best predictors of VRE acquisition. CONCLUSIONS: Among all other factors associated with VRE transmission, VRE acquisition may depend on room contamination, even after extensive cleaning. This study underscores the need for better cleaning and the role of the environment in transmission of VRE.

Attributable mortality of Stenotrophomonas maltophilia bacteremia.

A systematic evaluation of the attributable mortality of Stenotrophomonas maltophilia bacteremia was undertaken in a matched, retrospective, case-control study. We determined the attributable mortality rate (26.7%) and mortality risk ratio (an 8-fold increase) of S. maltophilia bacteremia. The attributable mortality rate for S. maltophilia bacteremia is similar to the attributable mortality rate for other nosocomial bloodstream infections.