The impact of multiple deprivation on the management of vestibular schwannomas.

PURPOSE: While some factors have been well-shown to affect the decision-making in treating patients with vestibular schwannomas (VS), little is known on the role of deprivation. Our objective was to assess the effect of socioeconomic background on the management of patients with VS. METHODS: This retrospective cohort study included 460 patients with sporadic VS from West of Scotland. The postcode-based, multifactorial Scottish Index of Multiple Deprivation (SIMD) was used to assess the socioeconomic background of each patient. We performed a multivariate analysis including tumour size, growth and patient age with management modality (observation, stereotactic radiotherapy, microsurgery) being the main outcome measure and outcome (need for additional treatment) an additional measure. RESULTS: We found no significant difference in the demographics, tumour characteristics and primary treatment choice between patients with different SIMD scores. In addition, there was no statistically significant difference in the growth occurrence rates following first-line treatment (p = 0.964) and in the second-line treatment choice (p = 0.460). CONCLUSIONS: Multiple deprivation does not affect decision making in patients with VS in the examined cohort. This is probably linked to the centralisation and uniformity of the service and might not necessarily be applicable to other health services without centralisation.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0-1, day 2-4 and day 6-8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54-70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002-0.064] and 0.041 [0.013-0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034-0.107], 0.060 [0.030-0.091] and 0.043 [0.001-0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006-0.071] and 0.023 [0.000-0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

Non-conventional immunomodulation in the management of sepsis.

Sepsis remains a critical global health issue, demanding novel therapeutic strategies. Traditional immunomodulation treatments such as corticosteroids, specific modifiers of cytokines, complement or coagulation, growth factors or immunoglobulins, have so far fallen short. Meanwhile the number of studies investigating non-conventional immunomodulatory strategies is expanding. This review provides an overview of adjunctive treatments with herbal-based medicine, immunonutrition, vasopressors, sedative treatments and targeted temperature management, used to modulate the immune response in patients with sepsis. Herbal-based medicine, notably within traditional Chinese medicine, shows promise. Xuebijing injection and Shenfu injection exhibit anti-inflammatory and immune-modulatory effects, and the potential to lower 28-day mortality in sepsis. Selenium supplementation has been reported to reduce the occurrence of ventilator-associated pneumonia among sepsis patients, but study results are conflicting. Likewise, the immune-suppressive effects of omega-3 fatty acids have been associated with improved clinical outcomes in sepsis. The immunomodulating properties of supportive treatments also gain interest. Vasopressors like norepinephrine exhibit dual dosage-dependent roles, potentially promoting both pro- and anti-inflammatory effects. Dexmedetomidine, a sedative, demonstrates anti-inflammatory properties, reducing sepsis mortality rates in some studies. Temperature management, particularly maintaining higher body temperature, has also been associated with improved outcomes in small scale human trials. In conclusion, emerging non-conventional immunomodulatory approaches, including herbal medicine, immunonutrition, and targeted supportive therapies, hold potential for sepsis treatment, but their possible implementation into everyday clinical practice necessitates further research and stringent clinical validation in different settings.

25-Hydroxyvitamin D concentrations do not affect the humoral or cellular immune response following SARS-CoV-2 mRNA vaccinations.

BACKGROUND: To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25[OH]D) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination. METHODS: In this prospective cohort study, blood samples were collected from 98 SARS-CoV-2 naive health care workers (HCW) receiving the first two doses of either BNT162b2 or mRNA-1273 in 2021. Wild-type spike (S) protein binding and neutralizing antibodies were determined approximately three weeks after the first dose and four to five weeks after the second dose. Antigen specific T-cells and functionality (proliferative response and interferon gamma [IFN-γ] release) were determined in 18 participants four weeks after the second dose of BNT162b2. We studied the association between 25(OH)D concentrations, which were determined prior to vaccination, and humoral and cellular immune responses following vaccination. RESULTS: We found no association between 25(OH)D concentrations (median 55.9 nmol/L [IQR 40.5-69.8]) and binding or neutralizing antibody titers after complete vaccination (fold change of antibody titers per 10 nmol/L 25(OH)D increase: 0.98 [95% CI 0.93-1.04] and 1.03 [95% CI: 0.96-1.11], respectively), adjusted for age, sex and type of mRNA vaccine. Subsequently, continuous 25(OH)D concentrations were divided into commonly used clinical categories (<25 nmol/L [n = 6, 6%], 25-49 nmol/L [n = 33, 34%], 50-75 nmol/L [n = 37, 38%] and ≥75 nmol/L [n = 22, 22%]), but no association with the humoral immune response following vaccination was found. Also, 25(OH)D concentrations were not associated with the SARS-CoV-2 specific T cell response. CONCLUSION: No association was found between 25(OH)D concentrations and the humoral or cellular immune response following mRNA vaccination against SARS-CoV-2. Based on our findings there is no rationale to advise vitamin D optimization preceding SARS-CoV-2 vaccination in HCW with moderate vitamin D status.

Mortality outcomes for Maori requiring renal replacement therapy during critical illness: a single unit audit in Aotearoa New Zealand.

BACKGROUND: Maori in New Zealand (NZ) are disproportionately affected by chronic kidney disease (CKD) and experience lower life expectancy on community dialysis compared with non-Maori. We previously identified a higher renal replacement therapy (RRT) requirement for Maori in our intensive care unit (ICU), the tertiary referral centre for NZ's Te Manawa Taki region. AIM: To describe mortality outcomes by ethnicity in the population requiring RRT in our ICU. METHODS: Retrospective audit of the Australia and NZ Intensive Care Society database for adult admissions to our general ICU from Te Manawa Taki between 2014 and 2018. Patients were stratified by non-RRT requirement (non-RRT), RRT-requiring acute kidney injury (AKI-RRT) and RRT-requiring end-stage renal disease (ESRD). RESULTS: Relative to the population of Te Manawa Taki, Maori were over-represented across all strata, especially ESRD (61.8%), followed by AKI-RRT (35.0%) and non-RRT (32.4%) (P < 0.001). There was no excess mortality by ethnicity in any stratum. Crude in-ICU mortality was similar by ethnicity among AKI-RRT (30.8% among Maori, vs 31.5%; P = 1.000) and ESRD (16.4% among Maori, vs 20.6%; P = 0.826). This trend remained at 1 year. Adjusted for clinically selected variables, neither AKI-RRT nor ESRD mortality was predicted by Maori ethnicity, both in-ICU and at 1 year. Irrespective of ethnicity, AKI-RRT patients had highest in-ICU mortality (31.2%; P < 0.001), while ESRD had highest 1-year mortality (46.1%; P < 0.001). CONCLUSION: Increased RRT requirement among Maori in our ICU is due to higher representation among ESRD. We did not demonstrate excess mortality by ethnicity in any stratum. AKI-RRT had higher in-ICU mortality than ESRD, but this reversed at 1 year.

A systematic review and meta-analysis of prophylactic medication of vestibular migraine.

OBJECTIVE: Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication. METHOD: A literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored. RESULTS: Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by -13.31 points and -4.16 points, respectively, and the Dizziness Handicap Inventory score by -32.24 and -21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control. CONCLUSION: Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant.

Six-canal video head impulse test in patients with labyrinthine and retrolabyrinthine pathology: detecting vestibulo-ocular reflex deficits.

BACKGROUND: Abnormal gains in six-canal video head impulse test are attributed to semi-circular canal deficits. However, as video head impulse test responses are linked to the vestibulo-ocular reflex, it was hypothesised that abnormal gains can be caused by vestibulo-ocular reflex pathway deficits. METHODS: This study compared video head impulse test gains in 20 patients with superior semi-circular canal dehiscence (labyrinthine cause) and 20 side- and gender-matched patients with vestibular schwannomas (retrolabyrinthine cause), and investigated correlations between them (Mann-Kendall trend test). RESULTS: Vestibular schwannoma but not superior semi-circular canal dehiscence was significantly associated with abnormal lateral (odds ratio = 9.00 (95 per cent confidence interval = 1.638-49.44), p = 0.011) and posterior (odds ratio = 9.00 (95 per cent confidence interval = 2.151-37.659), p = 0.003) canal status. In vestibular schwannoma patients, there was a statistically significant degree of dependence between all ipsilesional canal video head impulse test gains; such dependence was not observed in superior semi-circular canal dehiscence. CONCLUSION: Vestibulo-ocular reflex gains differ in patients with labyrinthine and retrolabyrinthine disease; this suggests that abnormal gains can indicate deficits not only in the semi-circular canals but also elsewhere along the vestibulo-ocular reflex pathway.

Maori Health Outcomes in Intensive Care Following Cardiac Surgery in Aotearoa New Zealand.

BACKGROUND: Maori, the indigenous peoples of Aotearoa New Zealand (NZ) experience disproportionately worse outcomes in cardiovascular health compared to non-Maori. Waikato Hospital provides tertiary cardiothoracic services to the Midland region of NZ, and has instituted an official policy to eliminate ethnic inequity in health. We aimed to audit the outcomes of our cardiothoracic intensive care unit (ICU) against this standard. METHOD: We analysed data from the prospectively-entered Australia and NZ Intensive Care Society database for all planned cardiothoracic ICU admissions from 2014 to 2018 at Waikato Hospital for patients aged 15-years and older (n=2,736). Outcomes measured were in-ICU, in-hospital, and 1-year mortality. RESULTS: Maori were under-represented in this cohort (17.9%) compared to the general Midland population. Maori patients were younger (median 60 vs 68-years old, p<0.001), were more commonly female (34.8% vs 23.6%, p<0.001), domiciled in more deprived areas (2018 NZ Index of Deprivation of 9 vs 6, p<0.001), and more likely to have rheumatic heart disease (35.6% vs 16.6%, p<0.001). More non-Maori required coronary vessel only surgery (57.4% vs 45.2%), whilst more Maori required valvular only surgery (41.1% vs 31.2%) (p<0.001 overall). Baseline Acute Physiology and Chronic Health Evaluation (APACHE) III risk of death score was higher for Maori (1.53% vs 0.89%, p<0.001), as was the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (2.04% vs 1.55%, p<0.001). Unadjusted mortality was higher for Maori in-ICU (3.1% vs 1.3%, p=0.005) and at 1-year (7.1% vs 3.8%, p=0.002). Adjusted in-ICU mortality, however, was predicted by combined coronary-valvular surgery (adjusted odds ratio, AOR 25.5 [95% confidence interval (CI) 3.30-348.46], p=0.005), Australia and New Zealand Risk of Death (ANZROD) score (AOR 1.11 [CI 1.05-1.19] p<0.001), and renal replacement therapy requirement (AOR 154.56 [CI 30.86-1,107.17] p<0.001), but not by Maori ethnicity (AOR 0.27 [CI 0.03-1.43] p=0.156). CONCLUSION: Our audit has identified significant inequity for Maori at our cardiothoracic ICU. Maori are sicker on presentation for planned cardiac surgery, as evidenced by higher admission severity scores, and experience higher unadjusted mortality up to 1-year compared to non-Maori. Maori also appear under-represented despite a greater burden of cardiovascular disease in the community. Further study is required to identify if upstream risk factors, including failure of early detection and referral for disease, contribute to these findings.

A systematic review of facial plastic surgery simulation training models.

OBJECTIVES: The coronavirus disease 2019 pandemic has led to a need for alternative teaching methods in facial plastics. This systematic review aimed to identify facial plastics simulation models, and assess their validity and efficacy as training tools. METHODS: Literature searches were performed. The Beckman scale was used for validity. The McGaghie Modified Translational Outcomes of Simulation-Based Mastery Learning score was used to evaluate effectiveness. RESULTS: Overall, 29 studies were selected. These simulated local skin flaps (n = 9), microtia frameworks (n = 5), pinnaplasty (n = 1), facial nerve anastomosis (n = 1), oculoplastic procedures (n = 5), and endoscopic septoplasty and septorhinoplasty simulators (n = 10). Of these models, 14 were deemed to be high-fidelity, 13 low-fidelity and 2 mixed-fidelity. None of the studies published common outcome measures. CONCLUSION: Simulators in facial plastic surgical training are important. These models may have some training benefits, but most could benefit from further assessment of validity.

[Clinical and economic impact of an ambulatory cataract surgery center without anesthesia in an area with poor ophthalmologic coverage]. / Impact médico-économique d'un centre de chirurgie ambulatoire de la cataracte sans parcours anesthésique dans un territoire en tension.

INTRODUCTION: The Ambulatory Clinic for Cataract Surgery (CACC) is a public department of the Bourges Medical Center, with a fast-track protocol without perioperative anesthesia care launched in 2015. This study aimed to evaluate the benefits of the CACC in terms of access to cataract surgery. METHODS: This retrospective study included all patients undergoing cataract surgery between 2012 and 2018. Data were collected from the French PMSI database. In order to evaluate the impact of the CACC, the surgical activity and change in indicators of patient flow and usage, as well as clinical and economic factors were analyzed. RESULTS: Between 2012 and 2018, with the same number of ophthalmologists, surgical activity increased by 50.2% in the Cher (vs. a mean increase of 22.7% in France). The patient loss ratio decreased by 5.9 points, the attraction and self-sufficiency ratios increased by 2.3 and 8.6 points respectively. The standardized rate of healthcare utilization for cataract surgery increased by 4.3 points (from 11.6 to 15.9 surgeries per 1000 inhabitants). As a result, Cher became the second highest French Department in 2018 in terms of utilization rate despite its 96th place out of 109 Departments in terms of density of ophthalmologists. CONCLUSION: The ambulatory cataract surgery center without anesthesia for selected patients might represent a solution in medical deserts to improve access to cataract surgery without increasing costs.

Maori health outcomes in an intensive care unit in Aotearoa New Zealand.

Maori are the indigenous people of New Zealand, and suffer disparate health outcomes compared to non-Maori. Waikato District Health Board provides level III intensive care unit services to New Zealand's Midland region. In 2016, our institution formalised a corporate strategy to eliminate health inequities for Maori. Our study aimed to describe Maori health outcomes in our intensive care unit and identify inequities. We performed a retrospective audit of prospectively entered data in the Australian and New Zealand Intensive Care Society database for all general intensive care unit admissions over 15 years of age to Waikato Hospital from 2014 to 2018 (n = 3009). Primary outcomes were in-intensive care unit and in-hospital mortality. The secondary outcome was one-year mortality. In our study, Maori were over-represented relative to the general population. Compared to non-Maori, Maori patients were younger (51 versus 61 years, P < 0.001), and were more likely to reside outside of the Waikato region (37.2% versus 28.0%, P < 0.001) and in areas of higher deprivation (P < 0.001). Maori had higher admission rates for trauma and sepsis (P < 0.001 overall) and required more renal replacement therapy (P < 0.001). There was no difference in crude and adjusted mortality in-intensive care unit (16.8% versus 16.5%, P = 0.853; adjusted odds ratio 0.98 (95% confidence interval 0.68 to 1.40)) or in-hospital (23.7% versus 25.7%, P = 0.269; adjusted odds ratio 0.84 (95% confidence interval 0.60 to 1.18)). One-year mortality was similar (26.1% versus 27.1%, P=0.6823). Our study found significant ethnic inequity in the intensive care unit for Maori, who require more renal replacement therapy and are over-represented in admissions, especially for trauma and sepsis. These findings suggest upstream factors increasing Maori risk for critical illness. There was no difference in mortality outcomes.

[Epidemiology of ocular emergencies in a non-university hospital: Clinical characteristics and severity grading according to the Base Score]. / Épidémiologie des urgences ophtalmologiques dans un centre hospitalier non universitaire : spécificités cliniques et sévérité selon le Base Score.

OBJECTIVE: This study aimed to analyse the epidemiological characteristics of ophthalmological emergencies at the Bourges Medical Center (CHB) and to identify factors associated with severity according to the Base Score in a region of France considered a healthcare desert. METHODS: All consecutive charts of patients seen for an eye-related condition between January 1 and April 30, 2019 in the ocular emergency department of the CHB were studied retrospectively. Seven demographic and nine medical variables were collected, and ocular severity was defined according to the Base Score. Linear regressions were performed to identify the factors associated with higher severity. RESULTS: 1809 patients were included (mean age: 53.3±22.7 years, 51.4% women), of whom 1619 (89.5%) were self-referred. Ocular surface disease (12.5%) was the most frequent diagnosis. The severity of the eye-related condition was significantly associated with the following factors: male gender, distance from home to the emergency department, presentation soon after the onset of symptoms, and referral from a physician (ophthalmologist or not). The regression coefficient was greater than 1 only for the patient referral pattern. CONCLUSION: The current study highlights that when patients with ocular emergencies can self-refer to an ocular emergency department within a French healthcare desert, 9 patients out of 10 self-refer. Referral from a physician is the main factor associated with ocular severity; thus, these cases should be considered severe until proven otherwise.

Predicting Ischemic Risk Using Blood Oxygen Level-Dependent MRI in Children with Moyamoya.

BACKGROUND AND PURPOSE: Moyamoya is a progressive steno-occlusive arteriopathy. MR imaging assessment of cerebrovascular reactivity can be performed by measuring the blood oxygen level-dependent cerebrovascular reactivity response to vasoactive stimuli. Our objective was to determine whether negative blood oxygen level-dependent cerebrovascular reactivity status is predictive of ischemic events in childhood moyamoya. MATERIALS AND METHODS: We conducted a retrospective study of a consecutive cohort of children with moyamoya who underwent assessment of blood oxygen level-dependent cerebrovascular reactivity. The charts of patients with written informed consent were reviewed for the occurrence of arterial ischemic stroke, transient ischemic attack, or silent infarcts. We used logistic regression to calculate the OR and 95% CI for ischemic events based on steal status. Hazard ratios for ischemic events based on age at blood oxygen level-dependent cerebrovascular reactivity imaging, sex, and moyamoya etiology were calculated using Cox hazards models. RESULTS: Thirty-seven children (21 female; median age, 10.7 years; interquartile range, 7.5-14.7 years) were followed for a median of 28.8 months (interquartile range, 13.7-84.1 months). Eleven (30%) had ischemic events, 82% of which were TIA without infarcts. Steal was present in 15 of 16 (93.8%) hemispheres in which ischemic events occurred versus 25 of 58 (43.1%) ischemic-free hemispheres (OR = 19.8; 95% CI, 2.5-160; P = .005). Children with idiopathic moyamoya were at significantly greater risk of ischemic events (hazard ratio, 3.71; 95% CI, 1.1-12.8; P = .037). CONCLUSIONS: Our study demonstrates that idiopathic moyamoya and the presence of steal are independently associated with ischemic events. The use of blood oxygen level-dependent cerebrovascular reactivity could potentially assist in the selection of patients for revascularization surgery and the direction of therapy in children with moyamoya.

Evaluation of plasma and erythrocyte fatty acids C15:0, t-C16:1n-7 and C17:0 as biomarkers of dairy fat consumption in adolescents.

INTRODUCTION: Pentadecanoic (C15:0), heptadecanoic (C17:0) and trans-palmitoleic (t-C16:1n-7) fatty acids (FAs) are often used as biomarkers for dairy fat in adults. This study aimed to investigate the relationship between dairy product intake and these FAs in adolescents. MATERIAL AND METHODS: Healthy adolescents were randomized to one of three groups (Group 1: control; Group 2: consume 3 dairy servings/day; and Group 3: consume ≥ 4 servings/d). C15:0, C17:0 and t-C16:1n-7 were quantified using gas chromatography. Dietary intakes were assessed by 24 h diet recalls. RESULTS: No difference was observed in FAs at baseline or 6 months (mo), however, at 12 mo, erythrocyte C15:0 increased in group 3 (+0.37 µg/ml, p = 0.01). Dairy intake increased in both intervention groups (Group 2: +1.4 servings/d; Group 3: +2.4 servings/d, p < 0.0001) and positively correlated with erythrocyte C15:0 at 12 mo. CONCLUSION: Erythrocyte FAs appear to be associated with increasing dairy intakes during adolescence.

Relationships Between Early Nutrition and Blood Glucose Concentrations in Very Preterm Infants.

OBJECTIVES: The aim of the study was to determine whether changes to early nutrition are associated with levels of glycemia in very preterm infants. METHODS: A retrospective, observational study of infants <1500 g or <30 weeks' gestation admitted to Neonatal Intensive Care, National Women's Hospital, New Zealand, before (Old Protocol) and after (New Protocol) a change in nutritional protocol. Nutritional intakes were calculated and averaged by day for postnatal days 1 to 7 (week 1) and 1 to 28 (month 1). Relationships between glycemia measures, macronutrient intakes, and achievement of 10% enteral feeds (≥10% total intake) were explored using logistic regression. RESULTS: Old Protocol (n = 190) and New Protocol (n = 267) groups had similar baseline characteristics. In week 1, New Protocol infants received more protein, less fat, and carbohydrate, had lower mean blood glucose concentrations (BGCs) (mean ±â€ŠSD 4.9 ±â€Š1.2 vs 5.6 ±â€Š1.4 mmoll/L, P < 0.0001), less hyperglycemia (BGC > 8.5 mmol/L, 71 [27%] vs 80 [42%], P = 0.0005), but similar hypoglycemia (BGC < 2.6). In month 1, New Protocol infants also had less hyperglycemia (105 [39%] vs 96 [51%], P = 0.02) and lower mean BGC (5.0 ±â€Š1.1 vs 5.5 ±â€Š1.1 mmol/L, P < 0.0001), but insulin usage was similar. After adjustment for birth weight z score and gestational age, hyperglycemia was significantly associated with week 1 intakes (g ·â€Škg ·â€Šday) of protein (odds ratio [95% confidence intervals] 0.47 [0.23-0.79], P = 0.004), fat (0.54 [0.40-0.74], P < 0.0001), and carbohydrate (1.25 [1.09-1.44], P < 0.0001). These relationships were similar for month 1. Each additional day to achieve 10% enteral feeds was associated with increased odds of hypoglycemia (1.09 [1.00-1.18], P = 0.04) and hyperglycemia (1.16 [1.06-1.28], P = 0.002). CONCLUSIONS: In very preterm infants, macronutrient balance and small, early enteral feeds may assist glycemic control.

Antineoplastic agents exacerbating Charcot Marie Tooth disease: red flags to avoid permanent disability.

BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common form of hereditary neuropathy. Due to the high prevalence of mild and undiagnosed forms, patients with CMT disease may be exposed to severe neurotoxicity following the administration of neurotoxic chemotherapies. The aim of this report is to alert oncologists to the potential to precipitate severe irreversible peripheral neuropathies when administering neurotoxic compounds to undiagnosed CMT patients. MATERIAL AND METHODS: A retrospective research in the OncoNeuroTox database was performed (2010-2016), searching for patients with the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN) and CMT disease. A comprehensive literature review for previously published cases was performed using the Pubmed and Cochrane databases (1972-2017). RESULTS: Among 428 patients with CIPN, we identified eight patients with concomitant CMT disease. Seven patients out of the eight had no previous diagnosis of CMT disease, although accurate familial history disclosed mild signs of peripheral neuropathy in five cases. Patients themselves had minor stigmata of long-standing peripheral damage. Patients received chemotherapy regimens based on vinca alkaloids, taxanes or a combination of vinca alkaloids and platinum compounds. In two cases, cumulative doses were below or equal to the expected neurotoxic threshold. Following chemotherapy administration, patients developed severe length-dependent sensory-motor deficits. Despite early drug discontinuation, most patients remained severely disabled. CONCLUSION: A brief checklist to disclose long-standing signs of peripheral neuropathy could be helpful to detect patients with undiagnosed hereditary neuropathies who could be at risk of developing severe irreversible neurotoxicity following the administration of neurotoxic agents.

Current status of atypical antipsychotics for the treatment of fibromyalgia.

The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study.

INTRODUCTION: Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression. METHODS: 23 patients with fibromyalgia and depressive symptomatology received 25-50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patient's global impression scale. RESULTS: Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects. DISCUSSION: Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.