Relationship between air pollution exposure and the progression of idiopathic pulmonary fibrosis in Madrid: Chronic respiratory failure, hospitalizations, and mortality. A retrospective study.

Introduction: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis. Objective: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis. Methods: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home. Results: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients. Conclusion: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration.

Introduction: Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF). Aim: This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF. Methods: This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 µM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment. Results: There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01-1.33] and OR and 95% CI = 1.80 [1.07-3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01-2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33-3.44], OR and 95% CI = 1.76 [1.15-2.66] and OR and 95% CI = 1.16 [1.03-1.3], respectively). Conclusion: This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.

The equations of ametropia: Predicting myopia

Why myopia develops, why it is reaching epidemic proportions and what is its cause are questions that puzzle many people. There is an answer to these questions and it is a simple one. This paper makes the connection between ametropic and in particular myopic development and theory to come with a summary of what we know about myopia and its governing equation.Key experiments, involving myopia and the effect of lenses in humans and animals have been done with unmistakable results. The observed effect of lenses implies a feedback mechanism. Feedback theory explains those results with mathematical precision. Disruption of emmetropization, is the mechanism behind ametropia and particularly myopia.Feedback theory for emmetropization was derived by observation of the input and output of the emmetropization feedback system in many patients. We show that it has the same equation as it is derived here independently from simple homeostasis principles.Classical observations and recent clinical studies have shown the association of many variables with myopia. They include near work, atropine, lenses, blur and outdoors versus indoors activities. We propose that human refractive development is controlled by homeostasis and based on that alone we derive the equation for the calculation of refraction for any patient and the effect of lenses.We provide software to calculate the refraction of any individual at any time.The editor of this journal makes the following statement: “This manuscript is intended for scientific discussion rather than clinical application. The present work does not intend to promote clinical under correction or no correction of myopia. Instead, clinicians should follow current clinical myopia management guidelines." (AU)

The equations of ametropia: Predicting myopia.

Why myopia develops, why it is reaching epidemic proportions and what is its cause are questions that puzzle many people. There is an answer to these questions and it is a simple one. This paper makes the connection between ametropic and in particular myopic development and theory to come with a summary of what we know about myopia and its governing equation. Key experiments, involving myopia and the effect of lenses in humans and animals have been done with unmistakable results. The observed effect of lenses implies a feedback mechanism. Feedback theory explains those results with mathematical precision. Disruption of emmetropization, is the mechanism behind ametropia and particularly myopia. Feedback theory for emmetropization was derived by observation of the input and output of the emmetropization feedback system in many patients. We show that it has the same equation as it is derived here independently from simple homeostasis principles. Classical observations and recent clinical studies have shown the association of many variables with myopia. They include near work, atropine, lenses, blur and outdoors versus indoors activities. We propose that human refractive development is controlled by homeostasis and based on that alone we derive the equation for the calculation of refraction for any patient and the effect of lenses. We provide software to calculate the refraction of any individual at any time. The editor of this journal makes the following statement: "This manuscript is intended for scientific discussion rather than clinical application. The present work does not intend to promote clinical under correction or no correction of myopia. Instead, clinicians should follow current clinical myopia management guidelines."

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price / Evolución del coste de medicamentos biológicos en pacientes con artritis reumatoide en un hospital terciario. Factores influyentes en dicha evolución

Objective: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. Methods: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. Results: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). Conclusion: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.(AU)

Objetivo: Evaluar la evolución del coste por paciente/año y del coste por paciente/año/medicamento en pacientes en tratamientos con biológicos con artritis reumatoide (AR). Analizar y cuantificar los factores influyentes en dicha evolución tales como la optimización de medicamentos biológicos, el uso de biosimilares y los descuentos oficiales y los obtenidos tras procedimientos negociados. Además, evaluar parámetros clínicos de la actividad propios de la enfermedad en dichos pacientes. Métodos: Estudio retrospectivo, observacional, realizado en un hospital terciario español. Se incluyeron pacientes adultos diagnosticados de AR en tratamiento con biológicos desde 2009 a 2017. Resultados: Se incluyeron 320, 270 y 389 pacientes en 2009, 2013 y 2017, respectivamente. El coste paciente/año disminuyó de 10.798€ en 2009, 7.491€ en 2013 a 7.116€ en 2017. En 2017, debido a la competencia establecida, se alcanzaron descuentos del 14 y del 29,5% en etanercept y su biosimilar; 11,5, 17,8, 17,9 y 17,3% en adalimumab, certolizumab, golimumab y tocilizumab IV, respectivamente, así como un 24,6% y 43,1% en infliximab y su biosimilar. El porcentaje de pacientes optimizados en 2017 alcanzó el 35.2%. El ahorro anual en 2017 fue de 1.288.535€ (830.000€ debido a la optimización de dosis y/o pautas de administración, 249.666€ correspondiente al 7,5% del descuento oficial y 208.868€ tras procedimientos negociados). Conclusión: El coste anual por paciente en AR disminuyó considerablemente debido a diferentes factores, tales como, descuentos en la adquisición de medicamentos debido a descuentos oficiales y procedimientos negociados, junto a la optimización de terapias, siendo este último el factor que más contribuyó en dicho descenso.(AU)

Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial.

BACKGROUND: DNA methylation-based estimators of biological age are reliable biomarkers of the ageing process. We aimed to investigate a range of epigenetic ageing biomarkers in a substudy of the NEAT001/ANRS143 clinical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxil fumarate and emtricitabine in antiretroviral therapy (ART)-naive adults. METHODS: We analysed frozen whole blood samples from 168 ART-naive participants with HIV from the NEAT001/ANRS143 trial, before ART initiation and after 2 years of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtricitabine). We also included 44 participants without HIV with a similar age and sex distribution. We analysed DNA methylation. Epigenetic age estimators (Horvath's clock, Hannum's clock, GrimAge, and PhenoAge) and estimated leucocyte compositions were generated using Horvath's New Online Methylation Age Calculator and Houseman's method. We calculated epigenetic age acceleration measures for each estimator of epigenetic age. The NEAT001/ANRS143 trial is registered with ClinicalTrials.gov, NCT01066962. FINDINGS: Compared with the HIV-uninfected group, ART-naive participants with HIV showed higher epigenetic age acceleration (EAA) according to all EAA estimators (mean 2·5 years, 95% CI 1·89-3·22 for Horvath-EAA; 1·4 years, 0·74-1·99 for Hannum-EAA; 2·8 years, 1·97-3·68 for GrimAge-EAA; and 7·3 years, 6·40-8·13 for PhenoAge-EAA), with all differences being statistically significant except for Hannum-EAA (Horvath-EAA p=0·0008; Hannum-EAA p=0·059; GrimAge-EAA p=0·0021; and PhenoAge-EAA p<0·0001). Epigenetic ageing was more pronounced in participants who had CD4 counts less than 200 cells per µL (significant for PhenoAge and Hannum's clock, p=0·0015 and p=0·034, respectively) or viral loads over 100 000 copies per mL at baseline (significant for PhenoAge, p=0·017). After 2 years of ART, epigenetic age acceleration was reduced, although PhenoAge and GrimAge remained significantly higher in participants with HIV compared with participants without HIV (mean difference 3·69 years, 95% CI 1·77-5·61; p=0·0002 and 2·2 years, 0·47-3·99; p=0·013, respectively). There were no significant differences in the ART effect on epigenetic ageing between treatment regimens. At baseline, participants with HIV showed dysregulation of DNA methylation-based estimated leucocyte subsets towards more differentiated T-cell phenotypes and proinflammatory leucocytes, which was also partly restored with ART. INTERPRETATION: ART initiation partly reversed epigenetic ageing associated with untreated HIV infection. Further studies are needed to understand the long-term dynamics and clinical relevance of epigenetic ageing biomarkers in people with HIV. FUNDING: NEAT-ID Foundation.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price.

OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price.

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.

The Severity of Hypoxic-Ischemic Encephalopathy Correlates With Multiple Organ Dysfunction in the Hypothermia Era.

OBJECTIVES: The objectives are to 1) determine whether there is a positive correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction and 2) evaluate the organ dysfunction pattern in infants with hypoxic-ischemic encephalopathy in the hypothermia era. DESIGN: Retrospective observational study of prospective data collected between April 2009 and December 2012. SETTING: The study took place in the neonatal ICU of Hospital Sant Joan de Déu-Hospital Clínic of Barcelona. PATIENTS: Prospective consecutive newborns with greater than or equal to 36 weeks of gestation, greater than or equal to 1,800 g of weight at birth, and a diagnosis of hypoxic-ischemic encephalopathy was included. INTERVENTIONS: Severity of hypoxic-ischemic encephalopathy was established before starting controlled hypothermia. Six organ systems and 23 clinical and laboratory variables were studied by means of an asymmetrical grading scale. Data were recorded daily during the first 72 hours of life. MEASUREMENTS AND MAIN RESULTS: Seventy-nine patients were studied. All presented with multiple organ dysfunction on day 1. There were differences in the number of affected organs on day 1 according to hypoxic-ischemic encephalopathy stage (p < 0.001). Scale scores correlated positively with the severity of hypoxic-ischemic encephalopathy (area under the curve ranged from 0.77 to 0.87 on every day studied). There were significant differences in the severity of dysfunction of each organ system among the three hypoxic-ischemic encephalopathy stages (p < 0.05). Although the most frequently involved were hepatic and pH and electrolyte imbalance, the most severely affected were the respiratory and cardiovascular systems. CONCLUSIONS: In the hypothermia era, multiple organ dysfunction continues to be almost universal in newborns with hypoxic-ischemic encephalopathy. There is a high correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction during the first 3 days of life. A high index of suspicion of relevant multiple organ dysfunction is required in infants admitted with a diagnosis of severe hypoxic-ischemic encephalopathy. Patients with moderate hypoxic-ischemic encephalopathy present wide variability in the severity of multiple organ dysfunction. In the absence of multiple organ dysfunction, a perinatal hypoxic-ischemic origin of acute severe neonatal encephalopathy should be carefully reconsidered.

Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults: HAE-QoL.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. OBJECTIVE: The objective of this study was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. METHODS: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. RESULTS: Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft version of the HAE-QoL was pilot tested in 332 patients, and accurate data were obtained from 290 patients from 11 countries. The reduction process resulted in a new version with 25 items and 7 dimensions (treatment difficulties, physical functioning and health, disease-related stigma, emotional role and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0.45 and 0.64, respectively) and with SF-36v2 dimensions (P < .004). HAE-QoL scores discriminated significantly among severity groups (median: asymptomatic 133.5 vs severe 84.0; P < .001); between patients with and without long-term prophylaxis (median: 101 vs 90; P = .001); and between patients with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). CONCLUSIONS: The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence.

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

BACKGROUND: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. METHODS: In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. RESULTS: Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15). CONCLUSIONS: Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

Efficacy and safety of nucleoside reverse transcriptase inhibitor-sparing salvage therapy for multidrug-resistant HIV-1 infection based on new-class and new-generation antiretrovirals.

BACKGROUND: The advent of new antiretrovirals has expanded the therapeutic options for multiple drug-resistant HIV-1 infection. The role of recycled nucleoside reverse transcriptase inhibitors (NRTIs) in this scenario remains uncertain. METHODS: Observational study of 122 consecutive patients with prior triple-class failure and multidrug-resistant HIV infection who started a salvage regimen with at least three of the new antiretrovirals darunavir, etravirine, raltegravir and maraviroc. Virological, immunological and clinical outcomes were compared according to the inclusion or not of NRTIs in the regimen, after 48 weeks of follow-up. RESULTS: All patients received at least two and 65% received three fully active drugs in the salvage regimen. In 63 patients recycled NRTIs were added to new drugs (NRTI-containing group) and 59 patients did not receive NRTIs (NRTI-sparing group). Both groups were comparable at baseline regarding the number of prior failures, resistance profile, CD4 cell count and HIV plasma viral load. The rates of HIV-1 RNA suppression below 50 copies/mL at week 48 (intent-to-treat analysis) were similar in the two groups: 46/59 [78%, 95% confidence interval (CI) 67%-88%] in the NRTI-sparing group and 49/63 (78%, 95% CI 67%-88%) in the NRTI-containing group. No significant differences were found in CD4 cell count increases. Drug-related adverse events leading to drug discontinuations only occurred in the NRTI-containing group (5 of 63, NRTI-related in 3 cases). CONCLUSIONS: The addition of NRTIs with reduced activity, according to genotypic resistance tests, does not seem to improve the efficacy of salvage regimens containing three of the new antiretrovirals in patients with multidrug-resistant HIV-1 infection.

Neonatal neurological morbidity associated with uterine rupture.

AIMS: To compare neonatal neurological morbidity associated with uterine rupture with morbidity associated with a non-reassuring fetal status. METHODS: We conducted a retrospective cohort analysis. Twenty-one cases of term infants delivered after a symptomatic uterine rupture were analyzed and compared with a randomly selected group of 63 infants born after a non-reassuring fetal heart rate pattern. RESULTS: Prevalence of uterine rupture was 0.058%. Maternal factors and infant general data were similar in both groups. Infants delivered after a uterine rupture had lower Apgar scores at 1 and 5 min, lower umbilical blood pH, and required more advanced resuscitation than infants delivered after a non-reassuring fetal status. Prevalence of hypoxic-ischemic encephalopathy in the uterine rupture group was 33%, compared with 5% in the other group (P<0.01, relative risk 3.7). Four infants in the uterine rupture group (19%) had moderate or severe encephalopathy; all of them had also multisystem dysfunction and an adverse outcome. No infant in the non-reassuring fetal status group showed moderate or severe encephalopathy. CONCLUSIONS: Uterine rupture is a considerable sentinel event that involves a high rate of early and late neurological morbidity in the newborn infant.

Compact laser radar and three-dimensional camera.

A novel three-dimensional (3D) camera is capable of providing high-precision 3D images in real time. The camera uses a diode laser to illuminate the scene, a shuttered solid-state charge-coupled device (CCD) sensor, and a simple phase detection technique based on the sensor shutter. The amplitude of the reflected signal carries the luminance information, while the phase of the signal carries range information. The system output is coded as a video signal. This camera offers significant advantages over existing technology. The precision in range is dependent only on phase shift and laser power and theoretically is far superior to existing time-of-flight laser radar systems. Other advantages are reduced size and simplicity and compact and inexpensive construction. We built a prototype that produced high-resolution images in range the (z) and x-y.

Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study).

OBJECTIVE: This study evaluated maintenance with lopinavir/ritonavir monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication. DESIGN: Randomized, controlled, open-label, multicenter, pilot clinical trial. METHODS: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for >1 month and had maintained serum HIV RNA <50 copies/mL for >6 months prior to enrollment. RESULTS: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/muL (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log10 viremia, or time with HIV RNA <50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained virally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/microL: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed. CONCLUSION: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides.

Cardiovascular support for low birth weight infants and cerebral hemodynamics: a randomized, blinded, clinical trial.

BACKGROUND: Maintaining adequate organ blood flow is the target of vasopressor treatment, but the impact of these measures on cerebral perfusion has not yet been evaluated systematically in a randomized, blinded, clinical trial. OBJECTIVES: To explore the effects on brain hemodynamics of 2 different inotropic agents used to treat systemic hypotension among low birth weight (LBW) infants. DESIGN AND METHODS: Newborns of <1501 g birth weight or <32 weeks' gestational age, with a mean blood pressure (MBP) lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (DP) (2.5, 5, 7.5, or 10 microg/kg per minute; n = 28) or epinephrine (EP) (0.125, 0.250, 0.375, or 0.5 microg/kg per minute; n = 32), at doses that were increased in a stepwise manner every 20 minutes until the optimal MBP (MBP-OP) was attained and maintained. OUTCOME MEASURES: Continuous monitoring of quantitative changes in cerebral concentrations of oxyhemoglobin and deoxyhemoglobin, cerebral intravascular oxygenation (HbD) (the difference between oxyhemoglobin and deoxyhemoglobin), and cerebral blood volume (CBV) were assessed with near-infrared spectroscopy. MBP, heart rate, transcutaneous Pco2 and Po2, and peripheral oxygen saturation were recorded continuously and analyzed at baseline, 20 minutes after each dose increase (T1, T2, T3, and T4) until MBP-OP was reached, and then every 20 minutes up to 1 hour of stable MBP-OP. RESULTS: Fifty-nine infants were considered for analysis. Patients did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks, respectively, in the DP group and 944 +/- 281 g and 27.7 +/- 2.4 weeks in the EP group). Studies were performed at a mean age of 5.3 +/- 3.7 hours of life (range: 2-16 hours). MBP-OP was attained for 96.3% of patients with DP and 93.7% with EP (responders). For those patients, MBP, heart rate, CBV, and HbD increased from baseline throughout the study period, with no differences between groups except for a higher heart rate with EP. Changes in MBP were correlated significantly with changes in HbD. Dose escalation of drugs produced no differences between groups in the behavior of the variables, except for a greater heart rate with EP from 20 minutes after dose 2 (T2) onward. Drug-induced changes in cerebral hemodynamics varied with gestational age; the EP-induced increase in CBV was greater among less mature patients (<28 weeks), whereas the DP-induced increase in CBV was greater among patients of > or =28 weeks. CONCLUSIONS: Among hypotensive LBW infants, cardiovascular support with low/moderate-dose DP or low-dose EP increased cerebral perfusion, as indicated by the increase in both CBV and HbD. Low-dose EP was as effective as low/moderate-dose DP in increasing MBP among LBW infants.

Vesicoureteral reflux: can the urethra be adequately assessed by using contrast-enhanced voiding US of the bladder?

PURPOSE: To prospectively evaluate contrast material-enhanced voiding ultrasonography (US) for assessment of the urethra by using voiding cystourethrography (VCUG) as the reference standard. MATERIALS AND METHODS: This study was approved by the ethics committee on human research. Written informed consent was obtained for all patients. A total of 146 pediatric patients suspected of having vesicoureteral reflux underwent US with a galactose-based contrast agent. The bladder was instilled with contrast agent and then filled with saline. US images of the urethra were videotaped before catheterization and during voiding. VCUG was subsequently performed in all patients. In female patients, the probe (a 3.5- or 5-MHz sector array or a 7.5-MHz linear transducer) was positioned longitudinally between the labia. In male patients, the transducer was placed longitudinally on the scrotum and then displaced distally toward the penile urethra. During voiding, attention was focused on the distention of the urethral walls and on the caliber of both the posterior and anterior urethra, which were measured with calipers. Sensitivity and specificity were estimated by using a confidence interval (CI) of 95%. RESULTS: All female patients and 75 male patients showed a normal urethra at both US and VCUG. Posterior urethral valves (PUV) were diagnosed in three patients at voiding US and were confirmed with findings from VCUG. Urethral stenosis was diagnosed in two male patients at voiding US and was confirmed with findings from VCUG. Seven male patients who had undergone surgery for PUV were adequately evaluated with both modalities. Sensitivity of voiding US was 100% (CI 95%: 96.5%, 100%); specificity was 100% (CI 95%: 69.9%, 100%). CONCLUSION: Voiding US is a reliable imaging modality for studying the urethra.

Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants.

HYPOTHESIS: Laying supine with the head in midline position improves cerebral venous return by preventing functional occlusion of the vessels of the neck. OBJECTIVES: To assess changes in cerebral blood volume (DeltaCBV) and cerebral blood flow (CBF) with the position of the head in ventilated patients using a noninvasive method. The influence of the type of ventilation and birth weight was evaluated. METHODS: Thirteen conventionally ventilated and 8 high-frequency oscillatory ventilated infants, with mean gestational ages and birth weights of 31 +/- 5 weeks (24--38) and 1575 +/- 803 g (560--3000), respectively, were studied 5.8 +/- 7.8 days (1--33) after birth. DeltaCBV (mL/100 g) and CBF (mL/100 g/min) were measured by near-infrared spectroscopy with the head in supine midline position (DeltaCBVs, CBFs) and rotated 90 to one side (DeltaCBVlat, CBFlat). Heart rate, peripheral saturation, transcutaneous PCO(2), and blood pressure were monitored continuously. Ventilatory settings remained constant throughout the study period. RESULTS: Mean DeltaCBVs was lower than mean DeltaCBVlat, although no changes in blood pressure, transcutaneous PCO(2), oxygenation, or heart rate occurred. This change in DeltaCBV was not associated with the type of ventilation or birth weight, but the differences tended to be greater (dDeltaCBV = DeltaCBVlat-DeltaCBVs) in the smallest infants (<1200 g). In contrast, CBF did not vary. CONCLUSION: The supine midline position of the head favors cerebral venous drainage and helps to prevent elevation of CBV. SPECULATION: This finding may be important in the first days of life, particularly in tiny preterm infants recovering from lung disease with improving lung compliance, in which functional obstruction of cerebral venous drainage should be avoided.