Colorectal cancer disease profile and treatment patterns at an urban tertiary hospital in Rwanda.

Background: The incidence of colorectal cancer (CRC) in sub-Saharan Africa (SSA) is rising, due to improving cancer registration efforts on one hand and an increasing westernisation of diets and lifestyle on the other as well as increasing rates of comorbidities. Methods: We present data for the clinical characteristics, pathology, treatments received, and survival outcomes of patients diagnosed with CRC at King Faisal Hospital (KFH) between January 2019 and May 2023. KFH is an urban tertiary hospital in Rwanda that provides chemotherapy and surgery to cancer patients. The data were extracted from electronic medical records, imaging and histopathology reports from the patient's time of diagnosis. We plotted Kaplan-Meier estimation of survival, defined as the time from presentation to death, within the study period (2019-2023). Results: Seventy-four patients diagnosed with CRC with complete information were identified in the KFH oncology records. The mean age at diagnosis was 54.6 years, with ages ranging between 22 and 81 years. At diagnosis, 24 (32.4%) patients were less than 50 years old and 29 (39.2%) were females. The rectum (36.5%) was the most common tumour location, and 58.1 tumours were left-sided. Most patients presented with Stage III (41.9%) or IV (35.1%) disease. Adenocarcinoma was the most common histological type (98.6%) including adenocarcinoma not otherwise specified (NOS) (86.5%), mucinous adenocarcinoma (10.8%), signet ring cell carcinoma (1.4%) and followed by squamous cell carcinoma (1.4%). In terms of treatment, 19 (25.7%) patients received only chemotherapy, 43 (58.1%) patients received neo-adjuvant or adjuvant chemotherapy, 9 (12.2%) of patients received both neo-adjuvant and adjuvant chemotherapy, 49 patients (66.2%) underwent surgery and 17 (23%) patients also received radiation. At the end of the follow up period, 63 (85.1%) patients remained in surveillance, 10 (13.5%) patients died, and 1 (1.3%) patient was lost to follow up. Mean overall survival was 45.5 (SD ± 2.0) months. Conclusion: CRC patients presented at an advanced stage and required complex treatment regimens at KFH. Further epidemiologic and molecular research is needed to characterise CRC incidence and presentation at a national level in Rwanda as increasing westernisation continues to change the face of CRC in urban areas of SSA.

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease.

Melanoma-associated leptomeningeal disease (M-LMD) occurs when circulating tumor cells (CTCs) enter into the cerebral spinal fluid (CSF) and colonize the meninges, the membrane layers that protect the brain and the spinal cord. Once established, the prognosis for M-LMD patients is dismal, with overall survival ranging from weeks to months. This is primarily due to a paucity in our understanding of the disease and, as a consequence, the availability of effective treatment options. Defining the underlying biology of M-LMD will significantly improve the ability to adapt available therapies for M-LMD treatment or design novel inhibitors for this universally fatal disease. A major barrier, however, lies in obtaining sufficient quantities of CTCs from the patient-derived CSF (CSF-CTCs) to conduct preclinical experiments, such as molecular characterization, functional analysis, and in vivo efficacy studies. Culturing CSF-CTCs ex vivo has also proven to be challenging. To address this, a novel protocol for the culture of patient-derived M-LMD CSF-CTCs ex vivo and in vivo is developed. The incorporation of conditioned media produced by human meningeal cells (HMCs) is found to be critical to the procedure. Cytokine array analysis reveals that factors produced by HMCs, such as insulin-like growth factor-binding proteins (IGFBPs) and vascular endothelial growth factor-A (VEGF-A), are important in supporting CSF-CTC survival ex vivo. Here, the usefulness of the isolated patient-derived CSF-CTC lines is demonstrated in determining the efficacy of inhibitors that target the insulin-like growth factor (IGF) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, the ability to intrathecally inoculate these cells in vivo to establish murine models of M-LMD that can be employed for preclinical testing of approved or novel therapies is shown. These tools can help unravel the underlying biology driving CSF-CTC establishment in the meninges and identify novel therapies to reduce the morbidity and mortality associated with M-LMD.

Post-discharge venous thromboembolism prophylaxis in hospitalized trauma patients: A retrospective comparison of patients receiving versus not receiving post-discharge prophylaxis.

BACKGROUND: Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization, but there is a paucity of evidence to guide the use of post-discharge prophylaxis (PDP). METHODS: A retrospective cohort study of trauma patients deemed moderate-to-high risk for VTE (risk assessment profile score [RAP] ≥5) who were prescribed PDP based on an internal clinical guideline assessing injury pattern and mobility status. PDP patients were compared with those that did not receive post-discharge prophylaxis (NPDP). RESULTS: 1512 patients were included. PDP group had higher mean RAP score (7.3 vs. 6.4, p â€‹< â€‹0.001), more likely to have a complex orthopedic fracture and underwent a longer median hospital (4.7 vs. 2.9 days, p â€‹< â€‹0.001). No difference between groups in 90-day VTE (11 [1.5 â€‹%] (PDP) vs. 8 [1.0 â€‹%] (NPDP), p â€‹= â€‹0.50), clinically relevant bleeding (p â€‹= â€‹0.58), or readmission (p â€‹= â€‹0.46). CONCLUSIONS: VTE incidence, clinically relevant bleeding, and readmission 90-days after hospital discharge were low and similar between PDP and NPDP groups. PDP prescribed in a presumably higher VTE risk trauma population may mitigate the long-term risk of VTE.

Using Regional Sero-Epidemiology SARS-CoV-2 Anti-S Antibodies in the Dominican Republic to Inform Targeted Public Health Response.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT80 for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

Delivery of the HIV Service and Telemedicine Through Effective Patient-Reported Outcomes (+STEP) Intervention to Increase Screening and Treatment of Mental Health and Substance Use Disorders for People Living With HIV in Alabama: Protocol for an Effectiveness-Implementation Study.

BACKGROUND: The syndemic of mental health (MH) and substance use disorders (SUDs) is common among persons living with HIV and jeopardizes HIV treatment adherence, engagement in care, and viral load suppression. Electronic patient-reported outcomes (ePROs), completed through tablet or computer, and telemedicine are evidence- and technology-based interventions that have been used to successfully increase screening and treatment, respectively, a model that holds promise for persons living with HIV. To date, there is limited guidance on implementing ePROs and telemedicine into HIV clinical practice even though it is well known that these evidence-based tools improve diagnosis and access to care. OBJECTIVE: To address this, we aim to conduct a multicomponent intervention for persons living with HIV, including the delivery of HIV services and telemedicine through effective ePROs (+STEP), to increase screening and treatment of MH and SUD in Ryan White HIV/AIDS Program (RWHAP)-funded clinics in Alabama. METHODS: Through this intervention, we will conduct a readiness, acceptability, and accessibility assessment and implement +STEP to improve the diagnosis and treatment of MH and SUD at RWHAP clinics in Alabama. To describe implementation strategies that address barriers to the uptake of +STEP in RWHAP clinics, we will conduct qualitative interviews in years 1 (early implementation), 2 (scale up), and 4 (maintenance) with patients and key staff to evaluate barriers, facilitators, and implementation strategies. Our Results will enable us to modify strategies to enhance +STEP penetration over time and inform the implementation blueprint, which we will develop for both RWHAP clinics in Alabama and future sites. We will assess the impact of implementing +STEP on diagnoses, referrals, and health care use related to MH, SUD, and HIV by comparing clinical outcomes from patients receiving these interventions (ePROs and telemedicine) with historical controls. RESULTS: The first study site began implementation in April 2022. A total of 2 additional sites have initiated ePROs. Final results are expected in 2026. The results of this study will provide a foundation for future research expanding access to ePROs for improved diagnosis linked to telemedicine access to accelerate patients along the continuum of care from MH and SUD diagnosis to treatment. CONCLUSIONS: Achieving the end of the HIV epidemic in the United States necessitates programs that accelerate movement across the MH and SUD care continuum from diagnosis to treatment for persons living with HIV. Scaling these services represents a path toward improved treatment outcomes with both individual health and population-level prevention benefits of sustained HIV viral suppression in the era of undetectable=untransmittable (U=U). This study will address this evidence gap through the evaluation of the implementation of +STEP to establish the necessary systems and processes to screen, identify, and better treat substance use and MH for people living with HIV. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40470.

A Study Protocol to Increase Engagement in Evidence Based Hospital and Community Based Care Using a Serious Injection Related Infections (SIRI) Checklist and Enhanced Peer for Hospitalized PWID (ShaPe).

Background: With the opioid crisis, surging methamphetamine use, and healthcare disruptions due to SARS-CoV-2, serious injection related infections (SIRIs), like endocarditis, have increased significantly. Hospitalizations for SIRI provide a unique opportunity for persons who inject drugs (PWID) to engage in addiction treatment and infection prevention, yet many providers miss opportunities for evidence-based care due to busy inpatient services and lack of awareness. To improve hospital care, we developed a 5-item SIRI Checklist for providers as a standardized reminder to offer medication for opioid use disorder (MOUD), HIV and HCV screening, harm reduction counseling, and referral to community-based care. We also formalized an Intensive Peer Recovery Coach protocol to support PWID on discharge. We hypothesized that the SIRI Checklist and Intensive Peer Intervention would increase use of hospital-based services (HIV, HCV screening, MOUD) and linkage to community-based care: PrEP prescription, MOUD prescription, and related outpatient visit(s). Methods: This is a feasibility study and randomized control trial of a checklist and intensive peer intervention for hospitalized PWID with SIRI admitted to UAB Hospital. We will recruit 60 PWID who will be randomized to one of 4 groups (SIRI Checklist, SIRI Checklist + Enhanced Peer, Enhanced Peer, and Standard of Care). Results will be analyzed using a 2x2 factorial design. We will use surveys to collect data on drug use behaviors, stigma, HIV risk, and PrEP interest and awareness. Our primary outcome of feasibility will include the ability to recruit hospitalized PWID and retain them in the study to determine post-discharge clinical outcomes. Additionally, we will explore clinical outcomes using a combination of patient surveys and electronic medical record data (HIV, HCV testing, MOUD and PrEP prescriptions).This study is approved by UAB IRB #300009134. Discussion: This feasibility study is a necessary step in designing and testing patient-centered interventions to improve public health for rural and Southern PWID. By testing low barrier interventions that are accessible and reproducible in states without access to Medicaid expansion and robust public health infrastructure, we aim to identify models of care that promote linkage and engagement in community care. Trial Registration: NCT05480956.

Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

Implementation and Impact of Critical Care Pharmacist Addition to a Telecritical Care Network.

Critical care pharmacists when incorporated into the ICU team, have been shown to improve outcomes in critically ill patients by decreasing mortality, improving morbidity and reducing cost. As telehealth continues to evolve, the incorporation of a critical care pharmacist into a comprehensive telecritical care (TCC) service will allow increased comprehensive pharmacotherapeutic care for those in smaller, community or rural hospitals. OBJECTIVES: To describe the implementation of a TCC pharmacist into an established TCC network, classify interventions performed, and quantify cost avoidance generated through pharmacist interventions. DESIGN: Multicenter, observational cohort study and retrospective return on investment, performed between December 2019 and December 2021. SETTING AND PARTICIPANTS: Critically ill adult patients, admitted to an ICU located in any of our eight community hospitals (50 ICU beds) within a large, 25-hospital integrated healthcare system (563 ICU beds total) in the United States. MAIN OUTCOMES AND MEASURES: The TCC pharmacist service was implemented in 8-hour shifts, initially available 5 days per week, then expanded to 7 days per week. Critical care pharmacist interventions were categorized by clinical type established utilizing American Society of Health-System Pharmacists benchmarking standards and the latest cost avoidance data. RESULTS: During the 2-year analysis period, TCC pharmacists documented 2,838 interventions generating $1,664,254 of gross cost avoidance and a return on investment of 4.5:1. CONCLUSIONS AND RELEVANCE: It is feasible to implement a TCC pharmacist within an established TCC network. Our experience showed enhanced comprehensive care of critically ill patients located in community hospitals within a large, integrated healthcare system, demonstrated significant cost avoidance, and has led to other initiatives, including a collaborative clinical/operational partnership with Life Flight.

SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.

Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. Funding: This study was funded by the US CDC.

Less Is More: A Multimodal Pain Management Strategy Is Associated With Reduced Opioid Use in Hospitalized Trauma Patients.

INTRODUCTION: Adequate pain control is critical to the management and recovery of acutely injured patients. Opioids are associated with various adverse effects, and drug overdose is the leading cause of injury-related death in the United States. We hypothesized that a multimodal pain management protocol would reduce opioid use while still optimizing pain control. METHODS: The study included the preanalysis (August 2017-September 2018) and postanalysis (October 2018-August 2019) of a multimodal pain management strategy implemented in hospitalized adult patients admitted to the trauma service at a single American College of Surgeons-verified level-1 trauma center. Patients less than 18 y of age, pregnant patients, or imprisoned patients were excluded. The primary endpoint was opioid prescription on discharge (morphine milligram equivalent [MME]). The secondary endpoints included inpatient MMEs, nonopioid adjunct use, and pain scores. Subgroup analysis evaluating opioid use based on Injury Severity Score groups (mild, moderate, or severe) and by the Abbreviated Injury Scale body region was performed. RESULTS: There were 1755 patients in the PRE group and 1723 patients in the POST group. MMEs prescribed on discharge decreased from median 15 (interquartile range: 37.5) to 1.2 (interquartile range: 22.5) (P < 0.001). More patients in the POST group were discharged opioid-free (44% versus 37%, P < 0.001). There was a significant increase in the use of all nonopioid pain medications. Pain scores did not change. Subgroup analysis revealed a significant decrease in discharge MMEs in mild and moderate Injury Severity Score groups and in all injured body regions except the chest. CONCLUSIONS: The implementation of a multimodal pain management protocol in trauma patients targeting scheduled nonopioid medications and patient education is feasible and is associated with reduced opioid amount prescribed on discharge, without compromising pain control.

Complications following surgical treatment of adolescent idiopathic scoliosis: a 10-year prospective follow-up study.

BACKGROUND: Accurate reporting of long-term complications of surgical treatment of adolescent idiopathic scoliosis (AIS) is critical, but incomplete. This study aimed to report on the rate of complications following surgical treatment of AIS among patients with at least 10 years of follow-up. METHODS: This was a retrospective review of prospectively collected data from a multicenter registry of patients who underwent surgical treatment for AIS with minimum 10-year follow-up. Previously published complications were defined as major if they resulted in reoperation, prolonged hospital stay/readmission, neurological deficits, or were considered life-threatening. Rates and causes of reoperations were also reviewed. RESULTS: Two hundred and eighty-two patients were identified with mean age at surgery of 14.6 ± 2.1 years. Mean follow-up was 10.6 (range 9.5-14) years. Eighty-seven patients had anterior spinal fusion (ASF); 195 had posterior spinal fusion (PSF). The overall major complication rate was 9.9% (n = 28) in 27 patients. Among PSF patients, the complication rate was 9.7% (n = 19) in 18 patients. The complications were surgical site infection (37%), adding-on (26%), pulmonary (16%), neurologic (11%), instrumentation (5%), and gastrointestinal (5%). In ASF patients, the complication rate was 10.3% (n = 9) among nine patients. The complications were pulmonary (44%), pseudoarthrosis (22%), neurologic (11%), adding-on (11%), and gastrointestinal (11%). The reoperation rate was 6.0% (n = 17) among 17 patients. Although most of the complications presented within the first 2 years (60.7%), surgical site infection and adding-on were also seen late into the 10-year period. CONCLUSION: This is the largest prospective study with at least a 10-year follow-up of complications following spinal fusion for AIS, the overall major complication rate was 9.9% with a reoperation rate of 6.0%. Complications presented throughout the 10-year period, making long-term follow-up very important for surveillance. LEVEL OF EVIDENCE: Therapeutic II.

Orthotopic Heart Auto-Transplantation in a Swine Model.

BACKGROUND AND AIM: The porcine heart bears the best resemblance to the human heart and remains the preferred preclinical model for anatomical, physiological, and medical device studies. In an effort to study phenomena related strictly to ischemia reperfusion and donor preservation protocols, it is essential to avoid the immune responses related to allotransplantation. Orthotopic auto-transplantation is a unique strategy to the field of cardiac transplantation for ex vivo experimentation. Nevertheless, auto-transplantation carries its own technical challenges related to insufficient length of the great vessels that are to be transected and re-anastomosed. METHODS: A novel method for orthotopic cardiac auto-transplantation in the porcine model was developed and was described herein. Porcine models were used for ex vivo experimentation of a novel device to study ischemia reperfusion injury. RESULTS: A total of five porcine models were used for ex vivo experimentation of a novel device to mitigate ischemia reperfusion injury and determine effects of donor preservation. Modifications to routine cardiac transplantation protocols to allow for successful auto-transplantation are described. CONCLUSION: Orthotopic cardiac auto-transplantation in the porcine model is a plausible and technically feasible method for reliable study of ischemia reperfusion injury and donor preservation protocols. Here, we describe methods for both direct orthotopic porcine cardiac auto-transplantations as well as a simplified protocol that can be substituted for full surgical auto-transplantation for the studies of preservation of donor hearts.

Sustained local inhibition of thrombin preserves renal microarchitecture and function after onset of acute kidney injury.

Acute kidney injury (AKI) management remains mainly supportive as no specific therapeutic agents directed at singular signaling pathways have succeeded in clinical trials. Here, we report that inhibition of thrombin-driven clotting and inflammatory signaling with use of locally-acting thrombin-targeted perfluorocarbon nanoparticles (PFC NP) protects renal vasculature and broadly modulates diverse inflammatory processes that cause renal ischemia reperfusion injury. Each PFC NP was complexed with ~13,650 copies of the direct thrombin inhibitor, PPACK (proline-phenylalanine-arginine-chloromethyl-ketone). Mice treated after the onset of AKI with PPACK PFC NP exhibited downregulated VCAM-1, ICAM-1, PGD2 prostanoid, M-CSF, IL-6, and mast cell infiltrates. Microvascular architecture, tubular basement membranes, and brush border components were better preserved. Non-reperfusion was reduced as indicated by reduced red blood cell trapping and non-heme iron. Kidney function and tubular necrosis improved at 24 hours versus the untreated control group, suggesting a benefit for dual inhibition of thrombosis and inflammation by PPACK PFC NP.

Weight-based enoxaparin dosing and deep vein thrombosis in hospitalized trauma patients: A double-blind, randomized, pilot study.

BACKGROUND: Venous thromboembolism is a cause of morbidity and mortality in trauma patients. Chemoprophylaxis with low-molecular-weight heparin at a standardized dose is recommended. Conventional chemoprophylaxis may be inadequate. We hypothesized that a weight-adjusted enoxaparin prophylaxis regimen would reduce the frequency of venous thromboembolism in hospitalized trauma patients and at 90-day follow-up. METHODS: This prospective, randomized pilot study enrolled adult patients admitted to a level 1 trauma center between July 2013 and January 2015. Subjects were randomized to receive either standard (30 mg subcutaneously every 12 hours) or weight-based (0.5mg/kg subcutaneously every 12 hours) enoxaparin. Surveillance duplex ultrasound for lower extremity deep vein thrombosis was performed on hospital days 1, 3, and 7, and weekly thereafter. The primary outcome was deep vein thrombosis during hospitalization. Secondary outcomes included venous thromboembolism at 90 days and significant bleeding events. RESULTS: Two hundred thirty-four (124 standard, 110 weight-based) subjects were enrolled. There was no difference between standard and weight-based regarding age, body mass index, percentage female gender, injury severity score, or percentage that had surgery. There was a trend toward less in-hospital deep vein thrombosis in weight-based (12 [9.7%] standard vs 4 [3.6%] weight-based, P = .075). At 90 days, there was no difference in venous thromboembolism (12 [9.7%] standard vs 6 [5.5%] weight-based, P =.34). There was 1 bleeding event, which occurred in a standard subject. CONCLUSION: Weight-based enoxaparin dosing for venous thromboembolism chemoprophylaxis in trauma patients may provide better protection against venous thromboembolism than standard. A definitive study is necessary to determine whether weight-based dosing is superior to standard.

Role of Cortical Auditory Evoked Potentials in Reducing the Age at Hearing Aid Fitting in Children With Hearing Loss Identified by Newborn Hearing Screening.

Recording of free-field cortical auditory evoked potential (CAEP) responses to speech tokens was introduced into the audiology management for infants with a permanent childhood hearing impairment (PCHI) during 2011-2015 at a U.K. service. Children with bilateral PCHI were studied from two sequential cohorts. Thirty-four children had followed an audiology pathway prior to CAEP introduction, and 44 children followed a pathway after the introduction of CAEP and were tested with unaided and aided CAEP responses. Data analysis explored the age of diagnosis, hearing aid fitting, and referral for cochlear implant (CI) assessment for each of these groups. CAEP offered a novel educative process for the parents and audiologists supporting decision-making for hearing aid fitting and CI referral. Delays in hearing aid fitting and CI referral were categorized as being due to the audiologist's recommendation or parental choice. Results showed that the median age of hearing aid fitting prior to CAEP introduction was 9.2 months. After the inclusion of CAEP recording in the infant pathways, it was 3.9 months. This reduction was attributable to earlier fitting of hearing aids for children with mild and moderate hearing losses, for which the median age fell from 19 to 5 months. Children with profound hearing loss were referred for CI assessment at a significantly earlier age following the introduction of CAEP. Although there has also been a national trend for earlier hearing aid fitting in children, the current study demonstrates that the inclusion of CAEP recording in the pathway facilitated earlier hearing aid fitting for milder impairments.

Seizure Prophylaxis in Patients with Traumatic Brain Injury: A Single-Center Study.

The use of prophylactic anticonvulsants to prevent early post-traumatic seizures (PTSs) is recommended but inconsistently employed in patients with traumatic brain injury (TBI). The authors evaluated outcomes associated with prophylaxis administration in patients with TBI at a Level 1 trauma center. All patients admitted with TBI from October 2007 through May 2012 were included. Our primary outcome was the incidence of early PTSs. Secondary outcomes included mortality, length of hospital and intensive care unit (ICU) stays, and incidence of late seizures. Of the 2,111 patients with TBI, 557 (26.4%) received seizure prophylaxis and 1,554 (73.6%) did not. Two early PTSs occurred in the prophylaxis group (0.4%), whereas 21 occurred in the non-prophylaxis group (1.4%) (p = 0.05). The overall mortality rate was higher in patients who received prophylaxis (14.2% vs. 6.2%; p < 0.001), and the mean hospital length of stay (LOS) was longer (6.8 ± 6.9 vs. 3.8 ± 5 days; p < 0.001). In patients with severe and moderate TBI, the rate of prophylaxis administration was approximately half, whereas significantly fewer patients with mild TBI received prophylaxis than did not (20.2% vs 79.8%, p < 0.001). Lower Glasgow Coma Scale (GCS) score and longer hospital LOS were associated with early PTS (p = 0.008 for both comparisons), but sex and age were not. Brain hemorrhage was present in 78.3% of those patients who experienced early seizures. In our cohort, patients who received seizure prophylaxis had a lower GCS score, higher overall mortality rate, longer LOS, and more frequent ICU admissions, suggesting that patients who received prophylaxis were likely more severely injured.

Risk of Resistant Organisms and Clostridium difficile with Prolonged Systemic Antibiotic Prophylaxis for Central Nervous System Devices.

BACKGROUND: Prolonged systemic antibiotic prophylaxis for central nervous system (CNS) devices may be associated with increased risk of antimicrobial resistance. The primary objective of this study was to determine the impact of prolonged CNS device antibiotic prophylaxis on the growth of resistant microorganisms and Clostridium difficile. METHODS: This retrospective, observational, cohort study included patients admitted to intensive care units with traumatic brain injury or other neurocritical illness. Patients who received a CNS device and antibiotic prophylaxis for at least 72 h were compared to patients with similar neurologic injuries who did not receive a CNS device. RESULTS: Study (n = 116) and control (n = 557) patients had mean APACHE II scores of 17.7 ± 9.2 and 15.1 ± 10.6 (p = 0.004) with 53.4 and 24.6 % receiving craniotomies (p < 0.001), respectively. Mean CNS device duration was 9.9 days, and 73 % of patients received cefuroxime for prophylaxis. The study cohort had a higher absolute incidence of resistant organisms compared with the control cohort (15.5 vs 4.1 %; odds ratio 1.93, 95 % CI 0.93-4.03, p = 0.078), though the study was underpowered to show statistical significance in multivariate analysis. C. difficile incidence was similar between groups (2.6 vs 2.0 %; odds ratio 1.45, 95 % CI 0.35-6.12, p = 0.61). CONCLUSION: We found a higher incidence of resistant organisms in patients receiving prolonged antibiotic prophylaxis with a CNS device, but similar incidence of C. difficile compared to controls. Lack of data supporting prolonged antibiotic prophylaxis for CNS devices and the risk of nosocomial infections with resistant organisms encourage limiting prophylactic antibiotics to a short periprocedural course.

Real-time ultrasound-guided needle injection of the mouse jugular vein.

This unit describes a novel method for direct venous injection into mice that offers potentially significant advantages over commonly used mouse vein injection techniques. This is achieved via percutaneous needle placement into the mouse jugular vein under real-time B-mode ultrasound (US) imaging. Real-time US imaging of the injection process allows for immediate determination of the overall success of injection. Unique, and potentially significant, advantages of this technique over others include: (1) direct visual confirmation of needle tip placement in the lumen of the vein, (2) immediate visual detection of extravascular extravasation of injectate, when compared to blinded techniques, such as tail vein injections, and (3) reduced morbidity and mortality compared to surgical vascular access techniques (i.e., jugular vein cannulation). This technique may lead to more accurate determination of the success of the injection procedure for each mouse, thus improving the quality of acquired data in dependent mouse experiments.

Predicting the type of hearing loss using click auditory brainstem response in babies referred from newborn hearing screening.

OBJECTIVES: This study examined the ability of click auditory brainstem response (ABR) undertaken below the age of 6 months (from expected date of delivery) to differentiate between conductive and sensorineural hearing loss (SNHL), using the latency of wave V measured 20 dB above threshold. DESIGN: Subjects were recruited if they had an ABR threshold of ≥ 40 dB nHL and ≤ 70 dB nHL in one or both ears measured below the age of 6 months and they had also attended follow-up appointments for behavioral assessment of their hearing in which the type of hearing loss had been confirmed. Forty-five children (84 ears) with SNHL, 82 children (141 ears) with temporary conductive hearing loss (TCHL), and 5 children (10 ears) with permanent conductive hearing loss (PCHL) were recruited. The differences between mean wave V latencies measured 20 dB above ABR threshold were examined using the independent t-test for the groups of cases with SNHL, TCHL, and PCHL. Signal-detection theory was used to examine the relationship between sensitivity and specificity when the latency of wave V 20 dB above threshold was used to identify the presence of SNHL. Receiver operating characteristics were generated and the coordinates of the curve examined for the best compromise between sensitivity and false-alarm rate. The specificity, positive predictive value, and probability of missing a true case were determined for the most promising criteria. RESULTS: There were significant differences between the two groups with SNHL and TCHL. The mean latency of wave V 20 dB above threshold was 1 msec shorter in those with SNHL compared with those with TCHL. There were significant differences between children with PCHL and SNHL but no difference between those with PCHL and TCHL. When a criterion of < 7.6 msec was chosen to predict the presence of SNHL the test sensitivity was 0.98, test specificity 0.71, and positive predictive value was 0.66. Nine out of 10 of those with a latency 20 dB above threshold of < 7.0 msec had an SNHL. CONCLUSIONS: The latency of wave V 20 dB above threshold measured using click ABR is a useful indicator of the type of hearing loss in babies referred from newborn hearing screening.

Predicting the degree of hearing loss using click auditory brainstem response in babies referred from newborn hearing screening.

OBJECTIVES: The predictive ability of the auditory brainstem response (ABR) is an important factor governing the program sensitivity of neonatal hearing screens. The study examined the accuracy of the click-evoked auditory brainstem response (ck-ABR) when undertaken below the age of 6 months (from expected date of delivery) in predicting the pure-tone thresholds subsequently found to be present in children with a congenital permanent childhood hearing impairment. DESIGN: Children with permanent childhood hearing impairment were ascertained from neonatal screening programs that have been subject to longitudinal evaluation. Ninety-two children who had ck-ABR recorded when below 6 months of age and repeatable ear specific pure-tone audiometry were recruited. Those with recognized temporary middle ear effusions at either test were excluded. The relationship between ABR and pure-tone thresholds was tested using the Pearson correlation coefficient with a linear regression model used to estimate pure-tone threshold (dependent variable) from ABR (independent variable). Correlation coefficients were obtained for pure-tone frequencies at octave intervals between 0.25 kHz and 4 kHz and at various frequency combinations. The difference between ABR and pure-tone threshold was analyzed. Those with a difference of greater than 20 dB were further examined. The ABR and pure-tone differences were also compared in babies born at term and prematurely. RESULTS: Of the 92 children recruited to the study two children had a confirmed auditory neuropathy spectrum disorder (2%) and 10 (11%) had an audiometrically confirmed progressive hearing impairment. When these children were excluded, there was a high linear positive correlation (r = 0.90, SE = 14.3 dB) between the ABR and pure-tone thresholds averaged at 2 to 4 kHz. Although the correlation varied for different audiometric configurations, in all cases with a sloping hearing loss the correlation with their best frequency was weaker than the correlation at 2 to 4 kHz. For the total cohort the mean difference between ABR and pure-tone thresholds averaged at 2 to 4 kHz was 4.4 dB (SD = 19.29). The modal difference was 0 dB (58%) and 76 % had a difference of 20 dB or less. ABR underestimated the subsequently recorded pure-tone thresholds by more than 20 dB in 11 children and 10 of these children showed progression of their hearing loss measured by serial pure-tone audiometry. ABR overestimated the pure-tone thresholds by more than 20 dB in 15 children. Nine of these children (60%) had suffered a perinatal illness and the mean difference between the pure-tone and ABR thresholds was significantly greater in those born at <35 weeks of gestation (p < 0.001). CONCLUSIONS: There is a high positive linear correlation between ck-ABR and pure-tone average thresholds at 2 to 4 kHz. However, the predictive value of ABR is reduced in certain neonatal groups. The cause for this is discussed as are the implications for undertaking a test battery at this age to improve the predictive accuracy.