Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to Fio2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/Fio2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

INTRODUCTION: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. METHODS: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). RESULTS: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. CONCLUSIONS: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.

The Effects of Chronic Steroid Use on Postoperative Complications Following Thyroidectomy.

BACKGROUND: Patients undergoing thyroidectomy are sometimes on chronic steroids for underlying disease. This study examined the postoperative risk profile of thyroidectomy patients on chronic steroids. METHODS: Patients in the National Surgical Quality Improvement Program (NSQIP) database who underwent thyroidectomy were sorted by presence or absence of chronic steroid use. Clinicodemographics, comorbidities, and postoperative complications were recorded and compared between the two. Univariate and multivariate analyses compared the groups and calculated odds ratios (OR). RESULTS: We identified 42,857 patients. 41,903 (97.8%) patients were not on chronic steroids, while 954 (2.2%) were. Most underwent total thyroidectomy (18,748, 43.75%) or total lobectomy (16,323, 38.09%). Following univariate and multivariate analyses, patients on chronic steroids had increased risk of postoperative bleeding and transfusions (OR = 0.375, p = 0.046, 95% CI 0.223-0.988), open wound infection (OR = 0.226, p < 0.001, 95% CI 0.117-0.437), pulmonary embolism (OR = 0.312, p = 0.034, 95% CI 0.106-0.918), and ventilator use > 48 h (OR = 0.401, p < 0.008, 95% CI 0.205-0.785). CONCLUSIONS: Chronic steroid use prior to thyroidectomy is an independent risk factor for multiple postoperative complications, namely postoperative bleeding and transfusions, open wound infection, pulmonary embolism, and ventilator use over 48 h. Patients on chronic steroids should be medically optimized before thyroidectomy to reduce the risk of potentially life-threatening complications.

Psychosocial Burden of Pediatric and Adult Patients With Congenital Versus Traumatic Facial Differences: Assessment of Psychiatric Distress and Healthcare Utilization in the United States From 2004 to 2012.

BACKGROUND: Psychiatric distress and its effects on healthcare utilization in pediatric patients with congenital and traumatic facial differences remain poorly understood. This study analyzes the psychosocial burden along with mental health and reconstructive surgery services utilization of this patient population in comparison with adult patients with such facial differences. METHODS: The 2004-2012 Medical Expenditures Panel Survey was queried for all patients with facial differences. Socioeconomic variables, Patient Health Questionnaire 2 and Kessler 6 scores, responses from validated screening surveys, and utilization of mental health and reconstructive surgery (ie, plastic surgery and otolaryngology) services were compared between pediatric and adult patients with congenital and traumatic facial differences. RESULTS: Children ages 5 to 12 years were more likely to be affected by facial trauma, whereas adolescents aged 13 to 17 years were more affected by congenital facial conditions. Pediatric patients with congenital facial conditions had higher rates of medical care, education, and special therapy utilization ( P < 0.0001), although their facial trauma counterparts used mental health services more often ( P < 0.0001). In adults, more facial trauma patients reported poorer perceived mental health status ( P = 0.01). Among patients with any facial difference, distressed adult patients were less likely to see a reconstructive surgeon even when controlling for socioeconomic variables (0.55 [0.31-0.97], P = 0.04). CONCLUSIONS: In the pediatric population, psychosocial considerations should include both age and etiology of facial differences to best optimize care. Among adults with facial trauma, poor mental health may contribute to lower rates of surgical follow-up, highlighting a potential benefit for provision of mental health services earlier for these patient populations.

Factors affecting periodontal healing of the adjacent second molar after lower third molar surgery: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aim to evaluate the effect modifiers which may influence the periodontal healing of the adjacent second molar after lower third molar surgery. MATERIALS AND METHODS: Prospective studies including patients with third molars requiring removal, with at least 6 months follow-up were considered. Outcomes were periodontal probing depth (PPD) reduction, final PPD, clinical attachment level (CAL) change, final CAL, alveolar bone defect (ABD) reduction, and final ABD depth. Meta-regression was performed to identify factors. RESULTS: Fourteen studies were included in the quantitative synthesis. At 6 months, the PPD reduction was 1.06 mm (95% CI, 0.72 to 1.39 mm) and the remaining PPD was 3.81 mm (95% CI, 3.00 to 4.62 mm). Baseline PPD was strongly correlated with the remaining PPD at 6 months (p < 0.001, adjusted R2 = 70.05%). CONCLUSIONS: Lower third molar surgery results in a modest reduction in PPD, CAL, and ABD; however, periodontal defects still remain at 6 months and beyond. Baseline PPD is strongly correlated with final PPD. While age is not shown to have effect on most of the periodontal parameters, a larger baseline PPD is more likely to manifest with increasing age and third molar surgery should be done before severe periodontitis occurs to avoid persistent periodontal defects. CLINICAL RELEVANCE: This study shows that lower third molar surgery results in modest improvement in periodontal parameters on adjacent second molars and identified factors such as baseline PPD which may affect the healing, which may guide the pre-, peri-, and post-operative management of lower third molar surgery.

Accuracy and safety of in-house surgeon-designed three-dimensional-printed patient-specific implants for wafer-less Le Fort I osteotomy.

OBJECTIVES: The design and fabrication of three-dimensional (3D)-printed patient-specific implants (PSIs) for orthognathic surgery are customarily outsourced to commercial companies. We propose a protocol of designing PSIs and surgical guides by orthognathic surgeons-in-charge instead for wafer-less Le Fort I osteotomy. The aim of this prospective study was to evaluate the accuracy and post-operative complications of PSIs that are designed in-house for Le Fort I osteotomy. MATERIALS AND METHODS: The post-operative cone beam computer tomography (CBCT) model of the maxilla was superimposed to the virtual surgical planning to compare the discrepancies of pre-determined landmarks, lines, and principal axes between the two models. Twenty-five patients (12 males, 13 females) were included. RESULTS: The median linear deviations of the post-operative maxilla of the x, y, and z axes were 0.74 mm, 0.75 mm, and 0.72 mm, respectively. The deviations in the principal axes for pitch, yaw, and roll were 1.40°, 0.90°, and 0.60°, respectively. There were no post-operative complications related to the PSIs in the follow-up period. CONCLUSIONS: The 3D-printed PSIs designed in-house for wafer-less Le Fort I osteotomy are accurate and safe. CLINICAL RELEVANCE: Its clinical outcomes and accuracy are comparable to commercial PSIs for orthognathic surgery. TRIAL REGISTRATION: Clinical trial registration number: HKUCTR-2113. Date of registration: 29 July 2016.

Management of Craniosynostosis in Lethal Perinatal Hypophosphatasia.

Although perinatal lethal hypophosphatasia (HPP) was once a disease with a universally poor prognosis, it has now become a rare but treatable condition with the advent of enzyme replacement therapy with asfotase alfa. As a result, a greater population of patients with perinatal HPP are presenting with abnormal head shape and craniosynostosis. The authors present here 3 cases of perinatal lethal HPP, 1 treated with traditional open cranial vault remodeling and 2 treated utilizing distraction osteogenesis techniques. All patients demonstrated outcomes comparable to those previously reported with traditional observation or open cranial vault repair. Thorough consideration and discussion between the surgical team and patient's family is needed to determine a treatment plan that best addresses the goals of patient and family in light of recent advances in medical treatment in this rare patient population in which surgical interventions were previously nearly impossible. This article further supports the safety and efficacy of surgical intervention and explores the utility of distraction osteogenesis to address craniosynostosis in this patient population.

To Operate or Not to Operate? Reconstructive Surgical Burden and Quality of Life of Pediatric Patients with Facial Differences.

OBJECTIVE: The Craniofacial Condition Quality of Life Scale (CFC-QoL) was used to evaluate the relationship between surgical burden and quality of life (QoL). DESIGN: Patient-parent dyads completed the CFC-QoL which queries the following QoL domains: Bullying, Peer Problems, Psychological Impact, Family Support, Appearance Satisfaction, and Desire for Appearance Change. Stepwise multivariate linear regressions were performed for each QoL domain. SETTING: Urban tertiary care center. PATIENTS, PARTICIPANTS: Pediatric patients with facial differences, and their parents. INTERVENTION: Survey study. MAIN OUTCOME MEASURE(S): Demographic, diagnostic, and surgical characteristics were collected. Surgical burden was calculated as the standard deviation from the mean number of surgeries per diagnostic cohort. RESULT: Patients (N = 168) were majority female (57.1%) and Hispanic (64.3%). Diagnoses were cleft lip and/or palate (CLP,n = 99) or other craniofacial conditions (CFC,n = 69). Average patient age was 2.3 ± 5.6 years at first reconstructive surgery and 12.3 ± 3.4 years at study enrollment. Patients received an average of 4.3 ± 4.1 reconstructive surgeries.Worse Bullying was associated with higher surgical burden. Worse Peer Problems was associated with higher surgical burden, but only for children with non-CLP CFCs. Worse Family Support was associated with CFC diagnosis, female sex, and higher surgical burden. Worse Psychological Impact was associated with higher surgical burden. Worse Appearance Satisfaction was associated with younger age and with lower surgical burden. Greater Desire for Appearance Change was associated with older age, higher surgical burden, CLP diagnosis, female sex, and non-Hispanic ethnicity. Socioeconomic status did not predict QoL per patient self- or parent-proxy report. CONCLUSIONS: Higher surgical burden was associated with worse QoL outcomes in multiple domains.

Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis.

BACKGROUND: Traumatic brain injuries (TBI) among military veterans are increasingly recognized as important causes of both short and long-term neuropsychological dysfunction. However, the association between TBI and the development of dementia is controversial. This systematic review and meta-analysis sought to quantify the risks of all-cause dementia including Alzheimer's diseases and related dementias (ADRD), and to explore whether the relationships are influenced by the severity and recurrence of head injuries. METHODS: Database searches of Medline, Embase, Ovid Healthstar, PubMed and PROSPERO were undertaken from inception to December 2020 and supplemented with grey literature searches without language restrictions. Observational cohort studies examining TBI and incident dementia among veterans were analysed using Dersimonian-Laird random-effects models. RESULTS: Thirteen cohort studies totalling over 7.1 million observations with veterans were included. TBI was associated with an increased risk of all-cause dementia (hazard ratio [HR] = 1.95, 95% confidence interval [CI]: 1.55-2.45), vascular dementia (HR = 2.02, 95% CI: 1.46-2.80), but not Alzheimer's disease (HR = 1.30, 95% CI: 0.88-1.91). Severe and penetrating injuries were associated with a higher risk of all-cause dementia (HR = 3.35, 95% CI: 2.47-4.55) than moderate injuries (HR = 2.82, 95% CI: 1.44-5.52) and mild injuries (HR = 1.91, 95% CI: 1.30-2.80). However, the dose-response relationship was attenuated when additional studies with sufficient data to classify trauma severity were included. CONCLUSION: TBI is a significant risk factor for incident all-cause dementia and vascular dementia. These results need to be interpreted cautiously in the presence of significant heterogeneity.

Functional outcomes at PICU discharge in hemato-oncology children at a tertiary oncology center in Hong Kong.

BACKGROUND: Advancements in cancer treatment have resulted in longer survival but often at the expense of new therapy-associated morbidities. The aim of this study is to evaluate functional outcomes of hemato-oncology patients at PICU discharge, and to identify associated risk factors. METHODS: A single-center retrospective observational study. All children (< 19 years) with a hemato-oncology diagnosis admitted to the Hong Kong Children's Hospital PICU over a 2-year period were included. Functional status upon admission and discharge were compared. Univariable and multi-variable analyses were employed to identify risk factors associated with new morbidities. RESULTS: Out of 288 PICU admissions, there were 277 live discharges (mortality 4%), of which 52 (18.8%) developed new morbidities. Emergency admission, severity of illness at admission, organ dysfunction and support were associated with new morbidities (OR 1.08-11.96; p < 0.05). Adjusting for confounding factors, higher Pediatric Logistic Organ Dysfunction 2 score at admission was significantly associated with development of new morbidities (OR 1.34; 95% CI 1.18-1.54; p < 0.001). CONCLUSION: Critically ill children with hemato-oncological diseases had a higher rate of developing new morbidities (18.8%) compared with the general PICU population (4-8%). This was associated with severity of illness at admission. Further work is warranted to understand the lasting effects of these new morbidities and mitigating interventions.

Clinical Characteristics and Outcomes of Acute Childhood Encephalopathy in a Tertiary Pediatric Intensive Care Unit.

AIM: Childhood encephalopathy comprises a wide range of etiologies with distinctive distribution in different age groups. We reviewed the pattern of encephalopathy admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital. METHODS: We reviewed the medical records and reported the etiologies, clinical features, and outcomes of children with encephalopathy. RESULTS: Twenty-four admissions to the PICU between April 2019 and May 2020 were reviewed. The median (interquartile range) age was 10.0 (14.7) years and 62.5% were boys. Confusion (66.7%) was the most common presentation. Adverse effects related to medications (33.3%) and metabolic disease (20.8%) were predominant causes of encephalopathies in our study cohort. Methotrexate was responsible for most of the medication-associated encephalopathy (37.5%), whereas Leigh syndrome, pyruvate dehydrogenase deficiency and Wernicke's encephalopathy accounted for those with metabolic disease. The median Glasgow Coma Scale (GCS) on admission was 12.5 (9.0). Antimicrobials (95.8%) and antiepileptic drugs (60.9%) were the most frequently given treatment. Children aged 2 years or younger were all boys (P = 0.022) and had a higher proportion of primary metabolic disease (P = 0.04). Intoxication or drug reaction only occurred in older children. The mortality was 8.3%, and over half of the survivors had residual neurological disability upon PICU discharge. Primary metabolic disease (P = 0.002), mechanical ventilation (P = 0.019), failure to regain GCS back to baseline level (P = 0.009), and abnormal cognitive function on admission (P = 0.03) were associated with cerebral function impairment on PICU discharge. CONCLUSIONS: Primary metabolic encephalopathy was prevalent in younger children, whereas drug-induced toxic encephalopathy was common among older oncology patients. Survivors have significant neurologic morbidity. Failure to regain baseline GCS was a poor prognostic factor for neurological outcomes.

Recommendations on the Management of Interhospital Transport of Pediatric Patients With Mediastinal Mass.

PURPOSE: Children with mediastinal masses often present with insidious symptoms to nonspecialist centers and require interhospital transport to oncology centers for definitive care. We evaluated clinical characteristics and patient outcomes and proposed a management protocol. MATERIALS AND METHODS: This is a retrospective review of all children with mediastinal mass at the pediatric intensive care unit of the Hong Kong Children's Hospital between April 2019 and March 2020. RESULTS: Ten children with a median age of 14.5 years (interquartile range, 9.3-17.0 years) were included. Leukemia and lymphoma accounted for the majority of cases (n = 6, 60%). Nearly all patients (n = 9, 90%) required interhospital transport before definitive treatment could be instituted. There were no deaths, but 2 patients were transported with significant respiratory compromise. Among patients requiring more than 1 interhospital transport, there was a higher incidence of shortness of breath (100% vs 40%; odds ratio, 33; P = 0.048) and orthopnea (80% vs 0%; odds ratio, 33; P = 0.048), whereas none had a neck mass (0% vs 80%; odds ratio, 0.03; P = 0.048). CONCLUSIONS: Children with mediastinal mass are at risk of life-threatening cardiorespiratory compromise. Pretransport assessment, planning, and stabilization along with clear management plans for deterioration during transport are crucial especially for patients who are symptomatic at time of presentation, to reduce risks associated with delays in arriving at the specialist point of care for definitive treatment.

The benefits of emotionally salient cues on event-based prospective memory in bipolar patients and schizophrenia patients.

Prospective memory (PM) refers to the ability to remember to carry out a delayed intention in the future. Evidence suggests that emotionally salient cues can enhance PM functions in healthy population, but whether the benefit exists in schizophrenia and bipolar patients remains unclear. This study aimed to examine and compare the potential enhancement effect of emotional PM cues in schizophrenia patients and bipolar patients. Twenty-eight clinically stable schizophrenia participants, 26 euthymic bipolar participants and 29 controls completed a computerized PM task involving PM cues with different types of valences (i.e., positive, neutral and negative). All the three groups showed better PM performance when negative PM cues were presented compared with positive and neutral PM cues. The sizes of the enhancement effects of negative PM cues were large (all Cohen's d ≥ 1.00) and comparable across three groups. Our findings suggested that patients with schizophrenia and bipolar disorders could benefit from negative PM cues to an extent similar to healthy individuals, thus extended the notion of psychosis continuum to the important area of emotion-cognition interaction.

Diagnostic Yield of Bronchoalveolar Lavage in Immunocompromised Children.

Results from early studies in the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised adults and children were variable. This prospective study aimed to determine the diagnostic yield of BALs in immunocompromised children over the first 18 months of service at a newly established children's hospital. Relationship between BAL results and changes in antimicrobial management was also studied. Twenty-one bronchoscopic BALs were performed on 18 children; 14 BALs (66.7%) yielded at least 1 pathogen and 7 (33.3%) yielded no pathogen. Two pathogens were found in 2 samples, and 1 pathogen was identified in 12 samples. Bacteria (n = 7 patients), viruses (n = 8 patients) and fungus (Pneumocycstis jirovecii in one patient) were yielded. Of the 21 BALs, 8 (38.1%) were associated with changes in antimicrobial management (Fisher's exact test, p = 0.018). No significant side effects such as pneumothorax or pulmonary hemorrhages were observed in this series. In conclusion, BAL in immunocompromised children is rewarding and has potential to impact on antimicrobial management.

Myocardial oedema in an 8-year-old Chinese boy with Idiopathic systemic capillary leak syndrome.

BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is rare, and there has been about 32 cases reported in children worldwide since this disorder was first described in 1960. Clinical guidelines on the management approach stemming from robust scientific evidence are lacking. This case report presents the first reported paediatric case of severe ISCLS with significant myocardial oedema and emphasizes this disease's impact on a child's cardiac function. CASE PRESENTATION: A Chinese boy had his first attack of severe hypovolaemic shock that responded to fluid resuscitation when he was 6 years of age. His second attack developed at 8 years of age. He was then transferred to our cardiac unit for refractory hypotensive shock. The patient's echocardiogram revealed ventricular wall thickening with significant cardiac dysfunction requiring extracorporeal membrane oxygenation support. Subsequently, he made a full recovery, including his myocardial wall thickness and function. The echocardiographic findings suggested myocardial oedema that was transient in nature. Clinical and laboratory investigation from both episodes were compatible with ISCLS. CONCLUSION: ISCLS is rare, and therefore there is only a limited understanding on the pathophysiology of this disorder. The current treatment approach is based on a few case reports and series. During the acute phase, optimal supportive management is paramount. Our case highlights the importance of early recognition and consideration for extracorporeal membrane oxygenation support in patients with a life-threatening presentation, as it was lifesaving for this child who suffered myocardial oedema and ventricular dysfunction.

Activators and repressors: A balancing act for X-inactivation.

In early female embryos X-chromosome inactivation occurs concomitant with up regulation of the non-coding RNA, Xist, on the future inactive X-chromosome. Up regulation of Xist and coating of the future inactive X is sufficient to induce silencing. Therefore unlocking the mechanisms of X-chromosome inactivation requires thorough understanding of the transcriptional regulators, both activators and repressors, which control Xist. Mouse pluripotent embryonic stem cells, which have two active X chromosomes, provide a tractable ex vivo model system for studying X-chromosome inactivation, since this process is triggered by differentiation signals in these cultured cells. Yet there are significant discrepancies found between ex vivo analyses in mouse embryonic stem cells and in vivo studies of early embryos. In this review we elaborate on potential models of how Xist is up regulated on a single X chromosome in female cells and how ex vivo and in vivo analyses enlighten our understanding of the activators and repressors that control this non-coding RNA gene.