Post-Traumatic Stress Disorder and Risk of Degenerative Synucleinopathies: Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review was conducted to answer whether adult-onset post-traumatic stress disorder (PTSD) is associated with increased risk of Parkinson's disease (PD) and related synucleinopathies. DESIGN: A systematic search of Medline (Ovid), Embase (Elsevier), PsycInfo (Ovid), Cochrane Library (Wiley), and Web of Science (Clarivate) was performed using MeSH headings and equivalent terms for PTSD, PD, DLB, and related disorders. SETTING: No restrictions. PARTICIPANTS: Eligible articles were published in peer-reviewed journals, sampled adult human populations, and treated PTSD and degenerative synucleinopathies as exposures and outcomes, respectively. MEASUREMENTS: Extracted data included diagnostic methods, sample characteristics, matching procedures, covariates, and effect estimates. Bias assessment was performed with the Newcastle-Ottawa scale. Hazard ratios were pooled using the random effects model, and the Hartung-Knapp adjustment was applied due to the small number of studies. RESULTS: A total of six articles comprising seven unique samples (total n = 1,747,378) met eligibility criteria. The risk of PD was reported in three retrospective cohort studies and one case-control study. Risk of DLB was reported in one retrospective cohort, one case-control, and one prospective cohort study. No studies addressed potential relationships with multiple system atrophy or pure autonomic failure. Meta-analysis of hazard ratios from four retrospective cohort studies supported the hypothesis that incident PTSD was associated with PD and DLB risk (pooled HR 1.88, 95% C.I. 1.08-3.24; p = 0.035). CONCLUSIONS: The sparse literature to-date supports further investigations on the association of mid- to late-life PTSD with Parkinson's and related neurodegenerative disorders.

High catalytic activity of heteropolynuclear cyanide complexes containing cobalt and platinum ions: visible-light driven water oxidation.

A near-stoichiometric amount of O2 was evolved as observed in the visible-light irradiation of an aqueous buffer (pH 8) containing [Ru(II) (2,2'-bipyridine)3 ] as a photosensitizer, Na2 S2 O8 as a sacrificial electron acceptor, and a heteropolynuclear cyanide complex as a water-oxidation catalyst. The heteropolynuclear cyanide complexes exhibited higher catalytic activity than a polynuclear cyanide complex containing only Co(III) or Pt(IV) ions as C-bound metal ions. The origin of the synergistic effect between Co and Pt ions is discussed in relation to electronic and local atomic structures of the complexes.

Physical Violence and Aggression in Parkinson's Disease: A Systematic Review.

BACKGROUND: Physical violence and aggression (PVA), defined as behaviors with the potential to cause bodily injury, are unfortunate risks in the management of all-cause neurodegenerative dementias. While dementia in Parkinson's disease (PD) may not be evident for many years after clinical onset, neuropsychiatric disturbances occur at all stages of the disease. At issue is whether PVA in PD is associated with clinical factors that can be targets for prevention and management in the absence of a prevailing dementia syndrome. OBJECTIVE: This systematic review examined the extent to which PVA in PD without dementia is a clinically significant concern and whether it is associated with factors that could warrant proactive management. METHODS: A systematic search of 9 electronic databases used MeSH headings and equivalent terms for PD, aggression, and violence. Eligible manuscripts were original articles that were published in peer-reviewed journals and reported on adults with PD in the awake state with PVA as possible outcomes. Extracted data included study design, PD ascertainment methods and characteristics, PVA assessment methods, subject demographics, psychiatric and medical comorbidities, and pertinent results. Inciting and confounding factors were extracted from case reports. Quality assessment tools were applied in accordance with the study design (e.g., observational, qualitative, or case report). RESULTS: The search identified 10 manuscripts: 2 observational quantitative studies (total n with PD = 545), 1 qualitative study (n with PD = 20), and 7 case reports (n = 7). The observational studies suggested that PVA is less common than other neuropsychiatric disturbances, but heterogeneous methods and quality concerns prevented further conclusions. In the case reports, all patients were male, and most were early onset. In 6 of the reports, PVA occurred in the context of bilateral subthalamic nucleus deep brain stimulation. CONCLUSIONS: PVA, while relatively rare in PD, can be a significant management issue that is associated with select premorbid characteristics and antiparkinsonian motor treatments. As PVA may be under-reported, further understanding of its frequency, causes, risk factors, and outcomes would benefit from its systematic assessment, ideally using self-report and informant-based questionnaires.

Noninvasive Ventilation or CPAP in the Initial Treatment Phase of Small Infants With Respiratory Failure.

BACKGROUND: Respiratory failure in infants is a common reason for admission to the pediatric ICU (PICU). Although high-flow nasal cannula (HFNC) is the preferred first-line treatment at our institution, some infants require CPAP or noninvasive ventilation (NIV). Here we report our experience using CPAP/NIV in infants < 10 kg. METHODS: We conducted a retrospective review of infants < 10 kg treated with CPAP/NIV in our PICUs between July 2017-May 2021 in the initial phase of treatment. Demographic, support type and settings, vital signs, pulse oximetry, and intubation data were extracted from the electronic health record. We compared subjects successfully treated with CPAP/NIV with those who required intubation. RESULTS: We studied 62 subjects with median (interquartile range) age 96 [6.5-308] d and weight 4.5 (3.4-6.6) kg. Of these, 22 (35%) required intubation. There were no significant differences in demographics, medical history, primary interface, pre-CPAP/NIV support, and device used to deliver CPAP/NIV. HFNC was used in 57 (92%) subjects before escalation to CPAP/NIV. Subjects who failed CPAP/NIV were less likely to have bronchiolitis (27% vs 60%, P = .040), less likely to be discharged from the hospital to home (68% vs 93%, P = .02), had a longer median hospital length of stay (LOS) (26.9 [21-50.5] d vs 10.4 [5.6-28.4] d, P = .002), and longer median ICU LOS (14.6 [7.9-25.2] d vs 5.8 [3.8-12.4] d, P = .004). Initial vital signs and FIO2 were similar, but SpO2 was lower and FIO2 higher at 6 h and 12 h after support initiation for subjects who failed CPAP/NIV. Initial CPAP/NIV settings were similar, but subjects who failed CPAP/NIV had higher maximum and final inspiratory/expiratory pressure. CONCLUSIONS: Most infants who failed initial HFNC support were successfully managed without intubation using NIV or CPAP. Bronchiolitis was associated with a lower rate of CPAP/NIV failure, whereas lower SpO2 and higher FIO2 levels were associated with higher rates of intubation.

High-Frequency Jet Ventilation in Infants With Congenital Heart Disease.

BACKGROUND: High-frequency jet ventilation (HFJV) is primarily used in neonates but may also have a role in the treatment of infants with congenital heart disease and severe respiratory failure. We hypothesized that HFJV would result in improved gas exchange in these infants. METHODS: We retrospectively reviewed the records of all pediatric patients with complex congenital heart disease treated HFJV in our pediatric cardiac ICU between 2014 and 2018. Patients in whom HFJV was started while on extracorporeal membrane oxygenation (ECMO) were excluded. We extracted data on demographics, pulmonary mechanics, gas exchange, the subsequent need for ECMO, use of inhaled nitric oxide, and outcomes. RESULTS: We included 27 subjects (median [interquartile range {IQR}] weight 4.4 [3.3-5.4] kg; median [IQR] age 2.5 [0.3-5.4] months), 22 (82%) of whom had cyanotic heart disease. Thirteen subjects (48%) survived and 6 (22%) required ECMO. HFJV was started after a median (IQR) of 8.4 (2.1-26.3) d of conventional mechanical ventilation. The subjects spent a median (IQR) of 1.2 (0.5-2.8) d on HFJV. The median (IQR) pre-HFJV blood gas results (n = 25) were pH 7.22 (7.17-7.31), [Formula: see text] 69 (51-77) mm Hg, and [Formula: see text] 51 (41-76) mm Hg. Median (IQR) initial HFJV settings were peak inspiratory pressure of 45 (36-50) cm H2O, breathing frequency of 360 (360-380) breaths/min, and inspiratory time of 0.02 (0.02-0.03) s. Compared with conventional mechanical ventilation, at 4-6 h after HFJV initiation, there were significant improvements in the median pH (7.22 vs 7.34; P = .001) and [Formula: see text] (69 vs 50 mm Hg; P = .001), respectively, but no difference in median [Formula: see text] (51 vs 53 mm Hg; P = .97). CONCLUSIONS: HFJV was associated with a decrease in [Formula: see text] and an increase in pH in infants with congenital heart disease who remained on HFJV 4 to 6 h after initiation.

High-Flow Nasal Cannula in Pediatric Critical Asthma.

BACKGROUND: High-flow nasal cannula (HFNC) has been used in the treatment of pediatric asthma, although high-quality data comparing HFNC to aerosol mask nebulizer are lacking. We hypothesized that HFNC would perform similarly to the aerosol mask for meaningful clinical outcomes in children with critical asthma. METHODS: We retrospectively reviewed the medical records of children with critical asthma (age 2-17 y) with a modified pulmonary index score (MPIS) ≥ 8 admitted to our pediatric ICU as part of a quality improvement project. Patients were managed with our MPIS-based, respiratory therapist-driven protocol. Subjects were divided into 2 cohorts by initial respiratory support: HFNC or aerosol mask. Data included demographics, initial respiratory support, and MPIS over time. Primary outcome was hospital length of stay (LOS). Secondary outcome was difference in MPIS over time. RESULTS: We included 171 subjects, with 104 in the HFNC group and 67 in the aerosol mask group. Median (interquartile range [IQR]) age was lower in the HFNC group (5 [IQR 4-9] vs 7 [IQR 5-10] y, P = .006)], while other demographic characteristics were similar. Initial MPIS was similar between HFNC and aerosol mask groups (11 [IQR 9-12] vs 10 [IQR 9-12], P = .15). There were no significant differences for hospital LOS (2.9 [IQR 2.1-3.9] vs 3.0 [IQR 2.3-4.4] d, P = .47), pediatric ICU LOS (1.9 [IQR 1.4-2.8] vs 1.8 [IQR 1.5-3.0] d, P = .92), or time to MPIS < 6 (1.0 [IQR 0.6-1.6] vs 1.3 [IQR 0.8-1.9) d, P = .09) between the HFNC and aerosol mask groups, respectively. Median time on continuous albuterol was shorter in the HFNC group compared to the aerosol mask group (1.0 [IQR 0.7-1.8] vs 1.5 [IQR 0.9-2.3] d, P = .048). Of note, 16 (24%) subjects in the aerosol mask group were eventually treated with HFNC. Use of a helium-oxygen mixture and noninvasive ventilation was similar between groups. CONCLUSIONS: HFNC performed similarly to aerosol mask in pediatric patients with critical asthma.

High-Frequency Jet Ventilation in Pediatric Acute Respiratory Failure.

BACKGROUND: High-frequency jet ventilation (HFJV) is primarily used in premature neonates; however, its use in pediatric patients with acute respiratory failure has been reported. The objective of this study was to evaluate HFJV use in the pediatric critical care setting. We hypothesized that HFJV would be associated with improvements in oxygenation and ventilation. METHODS: Medical records of all patients who received HFJV in the pediatric ICU of a quaternary care center between 2014 and 2018 were retrospectively reviewed. Premature infants who had not been discharged home were excluded, as were those in whom HFJV was started while on extracorporeal membrane oxygenation. Data on demographics, pulmonary mechanics, gas exchange, and outcomes were extracted and analyzed using chi-square testing for categorical variables, nonparametric testing for continuous variables, and a linear effects model to evaluate gas exchange over time. RESULTS: A total of 35 subjects (median age = 2.9 months, median weight = 5.2 kg) were included. Prior to HFJV initiation, median (interquartile range) oxygenation index (OI) was 11.3 (7.2-16.9), [Formula: see text] = 133 (91.3-190.0), pH = 7.18 (7.11-7.27), [Formula: see text] = 64 (52-87) mm Hg, and [Formula: see text] = 74 (64-125) mm Hg. For subjects still on HFJV (n = 25), there was no significant change in OI, [Formula: see text], or [Formula: see text] at 4-6 h after initiation, whereas pH increased (P = .001) and [Formula: see text] decreased (P = .001). For those remaining on HFJV for > 72 h (n = 12), the linear effects model revealed no differences over 72 h for OI, [Formula: see text], [Formula: see text], or mean airway pressure, but there was a decrease in [Formula: see text] while pH and [Formula: see text] increased. There were 9 (26%) subjects who did not survive, and nonsurvivors had higher Pediatric Index of Mortality 2 scores (P = .01), were more likely to be immunocompromised (P = .01), were less likely to have a documented infection (P = .02), and had lower airway resistance (P = .02). CONCLUSIONS: HFJV was associated with improved ventilation among subjects able to remain on HFJV but had no significant effect on oxygenation.

Initial Modified Pulmonary Index Score Predicts Hospital Length of Stay for Asthma Subjects Admitted to the Pediatric Intensive Care Unit.

BACKGROUND: Scoring systems are frequently used to assess the severity of pediatric asthma exacerbations. The modified pulmonary index score (MPIS) has been found to be highly correlated with length of stay (LOS) in the pediatric intensive care unit (PICU). We sought to evaluate the use of the MPIS to predict hospital LOS for patients admitted to our PICU. METHODS: We retrospectively reviewed the medical records of pediatric asthma subjects aged 2-17 y admitted to our PICU between June 2014 and November 2017. We divided subjects a priori into 3 groups (low: MPIS 0-5; medium: MPIS 6-9; high: MPIS ≥ 10) based upon each subject's first MPIS documented in the PICU. Hospital LOS, PICU LOS, time on continuous albuterol, and increased respiratory support were compared between groups. RESULTS: 143 subjects were included. There were no differences for demographics, medical history, cause of exacerbations, or mean heart rate between groups. There were significant differences between groups for mean breathing frequency (P < .001), [Formula: see text] (P = .01), and [Formula: see text] (P < .004). There were significant differences between groups for route of admission (P = .02), high-flow nasal cannula use (P < .001), and use of a helium-oxygen mixture (P < .001). There were significant differences between groups for median hospital LOS (1.2 vs 2.3 vs 3.4 d, P < .001), PICU LOS (0.39 vs 1.3 vs 2 d, P < .001), and time on continuous albuterol (7.4 vs 20.6 vs 34.7 h, P < .001). After adjusting for demographics and medical history, the incidence risk ratio for hospital LOS was 2.09 for PICU admission for an MPIS of 6-9 and 2.68 for an MPIS ≥ 10 when compared to an MPIS < 6. CONCLUSIONS: The MPIS thresholds used in our pathway appropriately predicted LOS in our cohort of subjects with asthma admitted to the PICU. Higher MPIS was associated with increased hospital LOS, PICU LOS, and time on continuous albuterol.

A Respiratory Therapist-Driven Asthma Pathway Reduced Hospital Length of Stay in the Pediatric Intensive Care Unit.

BACKGROUND: Asthma is a common reason for admissions to the pediatric intensive care unit (PICU). Since June 2014, our institution has used a pediatric asthma clinical pathway for all patients, including those in PICU. The pathway promotes respiratory therapist-driven bronchodilator weaning based on the Modified Pulmonary Index Score (MPIS). This pathway was associated with decreased hospital length of stay (LOS) for all pediatric asthma patients; however, the effect on PICU patients was unclear. We hypothesized that the implementation of a pediatric asthma pathway would reduce hospital LOS for asthmatic patients admitted to the PICU. METHODS: We retrospectively reviewed the medical records of all pediatric asthma subjects 2-17 y old admitted to our PICU before and after pathway initiation. Primary outcome was hospital LOS. Secondary outcomes were PICU LOS and time on continuous albuterol. Data were analyzed using the chi-square test for categorical data, the t test for normally distributed data, and the Mann-Whitney test for nonparametric data. RESULTS: A total of 203 eligible subjects (49 in the pre-pathway group, 154 in the post group) were enrolled. There were no differences between groups for age, weight, gender, home medications, cause of exacerbation, medical history, or route of admission. There were significant decreases in median (interquartile range) hospital LOS (4.4 [2.9-6.6] d vs 2.7 [1.6-4.0] d, P < .001), median PICU LOS (2.1 [1.3-4.0] d vs 1.6 [0.8-2.4] d, P = .003), and median time on continuous albuterol (39 [25-85] h vs 27 [13-42] h, P = .001). Significantly more subjects in the post-pathway group were placed on high-flow nasal cannula (32% vs 6%, P = .001) or noninvasive ventilation (10% vs 4%, P = .02). CONCLUSION: The implementation of an asthma pathway was associated with decreased hospital LOS, PICU LOS, and time on continuous albuterol. There was also an increase in the use of high-flow nasal cannula and noninvasive ventilation after the implementation of this clinical pathway.