RESUMEN
BACKGROUND: Numerous randomised clinical trials and real-world studies have supported the safety of paclitaxel-coated devices for the treatment of femoropopliteal occlusive disease. However, a 2018 summary-level meta-analysis suggested an increased mortality risk for paclitaxel-coated devices compared with uncoated control devices. This study presents an updated analysis of deaths using the most complete and current data available from pivotal trials of paclitaxel-coated versus control devices. METHODS: Ten trials comparing paclitaxel-coated versus control devices were included in a patient-level pooled analysis. Cox regression models were used to evaluate the effect of paclitaxel exposure on risk of death in both intention-to-treat (ITT; primary analysis) and three as-treated analysis sets accounting for treatment group crossover at the index procedure and over time. The effect of paclitaxel dose and baseline covariates were also evaluated. FINDINGS: A total of 2666 participants were included with a median follow-up of 4·9 years. No significant increase in deaths was observed for patients treated with paclitaxel-coated devices. This was true in the ITT analysis (hazard ratio [HR] 1·14, 95% CI 0·93-1·40), the as-treated analysis (HR 1·13, 95% CI 0·92-1·39), and in two crossover analyses: 1·07 (0·87-1·31) when late crossovers were censored and 1·04 (0·84-1·28) when crossovers were analysed from the date of paclitaxel exposure. There was no significant effect of paclitaxel dose on mortality risk. INTERPRETATION: This meta-analysis found no association between paclitaxel-coated device exposure and risk of death, providing reassurance to patients, physicians, and regulators on the safety of paclitaxel-coated devices. FUNDING: Becton Dickinson, Boston Scientific, Cook, Medtronic, Philips, Surmodics, and TriReme Medical.
Asunto(s)
Fármacos Cardiovasculares , Enfermedad Arterial Periférica , Humanos , Paclitaxel/efectos adversos , Enfermedad Arterial Periférica/tratamiento farmacológico , Arteria Femoral , Factores de Tiempo , Boston , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Patients with no-option chronic limb-threatening ischemia (no-option CLTI) have limited therapeutic options. The PROMISE II study evaluated, transcatheter arterialization of deep veins (TADV) as a treatment option for no-option CLTI. In the current study patients from PROMISE II were compared to patients from a registry of untreated no-option CLTI patients (CLariTI: Natural Progression of High-Risk Chronic Limb-Threatening Ischemia). METHODS: We used propensity matching to compare patients from the PROMISE II prospective study of the TADV intervention with simultaneously enrolled CLTI patients that were note candidates for PROMISE II but were enrolled in to CLariTI natural history registry. Untreated no-option CLTI (CLariTI) patients could either be no-option or patients who did not meet PROMISE II entry criteria. Risk difference between groups was calculated using common risk difference and P values were provided by propensity-score stratified Mantel-Haenszel test. The primary endpoint was amputation-free survival (AFS). RESULTS: Diabetes was present in over 75% of patients. All patients had tissue loss and 35-46% had extensive tissue loss (Rutherford 6). The unadjusted AFS at 6 months, was 66.1% by Kaplan-Meier estimate for PROMISE II patients (n = 105) compared to 39.1% in the no-option cohort of CLariTI (n = 121) and 44.0% in the full cohort (no-option and patients not meeting entry criteria combine, n = 180). The treatment group who underwent TADV for no-option CLTI had an absolute difference of 29% improved (P < 0.0001) propensity-adjusted risk difference in AFS and a relative event rate reduction of 45% compared to the no-option control patients. CONCLUSIONS: Transcatheter arterialization of deep veins (TADV) resulted in improved 6 month AFS in no-option CLTI patients and appears to be a promising therapy in patients with no-option CLTI.
Asunto(s)
Procedimientos Endovasculares , Enfermedad Arterial Periférica , Humanos , Isquemia Crónica que Amenaza las Extremidades , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Resultado del Tratamiento , Estudios Prospectivos , Nivel de Atención , Factores de Riesgo , Isquemia/diagnóstico por imagen , Isquemia/cirugía , Recuperación del Miembro/métodos , Enfermedad Crónica , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. METHODS: Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. RESULTS: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. CONCLUSIONS: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.
Asunto(s)
Angioplastia de Balón/mortalidad , Análisis de Datos , Stents Liberadores de Fármacos , Paclitaxel/administración & dosificación , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/terapia , Angioplastia de Balón/tendencias , Stents Liberadores de Fármacos/tendencias , Humanos , Mortalidad/tendencias , Ensayos Clínicos Controlados Aleatorios como Asunto/métodosRESUMEN
Endothelial dysfunction is a hallmark of pulmonary arterial hypertension (PAH) but there are no established methods to study pulmonary artery endothelial cells (PAECs) from living patients. We sought to culture PAECs from pulmonary artery catheter (PAC) balloons used during right-heart catheterisation (RHC) to characterise successful culture attempts and to describe PAEC behaviour.PAECs were grown in primary culture to confluence and endothelial cell phenotype was confirmed. Standard assays for apoptosis, migration and tube formation were performed between passages three to eight. We collected 49 PAC tips from 45 subjects with successful PAEC culture from 19 balloons (39%).There were no differences in subject demographic details or RHC procedural details in successful versus unsuccessful attempts. However, for subjects who met haemodynamic criteria for PAH, there was a higher but nonsignificant (p=0.10) proportion amongst successful attempts (10 out of 19, 53%) versus unsuccessful attempts (nine out of 30, 30%). A successful culture was more likely in subjects with a lower cardiac index (p=0.03) and higher pulmonary vascular resistance (p=0.04). PAECs from a subject with idiopathic PAH were apoptosis resistant compared to commercial PAECs (p=0.04) and had reduced migration compared to PAECs from a subject with portopulmonary hypertension with high cardiac output (p=0.01). PAECs from a subject with HIV-associated PAH formed fewer (p=0.01) and shorter (p=0.02) vessel networks compared to commercial PAECs.Sustained culture and characterisation of PAECs from RHC balloons is feasible, especially in PAH with high haemodynamic burden. This technique may provide insight into endothelial dysfunction during PAH pathogenesis.
Asunto(s)
Arteria Pulmonar , Enfermedades Vasculares , Catéteres , Células Cultivadas , Células Endoteliales , Humanos , PulmónRESUMEN
BACKGROUND: Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. METHODS: RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic-diastolic hypertension aged 18-75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. FINDINGS: Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (-8·5 mm Hg, SD 9·3) than with the sham procedure (-2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: -6·3 mm Hg, 95% CI -9·4 to -3·1, p=0·0001). No major adverse events were reported in either group. INTERPRETATION: Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic-diastolic hypertension in the absence of medications. FUNDING: ReCor Medical.
Asunto(s)
Desnervación/métodos , Procedimientos Endovasculares/métodos , Hipertensión/cirugía , Riñón/inervación , Riñón/cirugía , Arteria Renal/inervación , Adolescente , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial/tendencias , Femenino , Humanos , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Renal/cirugía , Método Simple Ciego , Resultado del Tratamiento , Ultrasonografía/instrumentación , Adulto JovenRESUMEN
High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55â years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1â µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.
Asunto(s)
Enfermedades del Tejido Conjuntivo/complicaciones , Sulfato de Deshidroepiandrosterona/sangre , Estradiol/sangre , Cardiopatías Congénitas/complicaciones , Hipertensión Pulmonar/sangre , Posmenopausia/sangre , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Prueba de PasoRESUMEN
Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct type of pulmonary hypertensive disease, characterized by incomplete or abnormal resolution of acute pulmonary embolism such that residual emboli become organized and fibrotic. CTEPH can occur in patients without a prior history of venous thromboembolism, and is diagnosed based on precapillary pulmonary hypertension on right heart catheterization with evidence of chronic emboli on ventilation/perfusion scan, chest imaging, or pulmonary angiogram. Pulmonary endarterectomy (PEA) is often curative, and results in improved survival. In patients for whom PEA is not feasible, medical therapy has been effective in improving hemodynamics and functional capacity.
Asunto(s)
Hipertensión Pulmonar/etiología , Embolia Pulmonar/complicaciones , Cateterismo Cardíaco/métodos , Enfermedad Crónica , Endarterectomía/métodos , Hemodinámica , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Arteria Pulmonar/patología , Embolia Pulmonar/terapiaRESUMEN
BACKGROUND: Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. METHODS: We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. RESULTS: We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL- compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P < .01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P < .01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P = .01 at 14 days post-treatment; 1 trial). CONCLUSION: AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.
Asunto(s)
Antimaláricos/farmacología , Artemisininas/farmacología , Culicidae/parasitología , Etanolaminas/farmacología , Fluorenos/farmacología , Malaria Falciparum , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/uso terapéutico , Arteméter , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Humanos , Lumefantrina , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE OF REVIEW: Pulmonary hypertension is a common complication of systemic sclerosis (SSc), and remains a leading cause of morbidity and mortality. We will review recent developments in the recognition, classification and treatment of pulmonary hypertension in SSc. RECENT FINDINGS: Advances in screening for pulmonary arterial hypertension (PAH) and use of exercise haemodynamics may help to identify pulmonary vascular disease earlier in SSc. Recent studies have led to changes in recommendations for adjunct therapy and selection of pulmonary vasodilators for the treatment of SSc-associated PAH. SUMMARY: Recent advances in the diagnosis, classification and management of pulmonary hypertension in SSc have continued to improve our understanding of this challenging disease. Ongoing investigation in the pathogenesis of this disease will afford the opportunity to develop targeted therapies to improve outcomes for SSc patients with pulmonary hypertension.
Asunto(s)
Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Esclerodermia Sistémica/complicaciones , Vasodilatadores/uso terapéutico , Humanos , Hipertensión Pulmonar/clasificaciónRESUMEN
OBJECTIVES: Pulmonary vascular dysfunction is associated with adverse prognosis in patients with the acute respiratory distress syndrome; however, the prognostic impact of pulmonary arterial compliance in acute respiratory distress syndrome is not established. DESIGN, SETTING, PATIENTS: We performed a retrospective analysis of 363 subjects with acute respiratory distress syndrome who had complete baseline right heart catheterization data from the Fluid and Catheter Treatment Trial to test whether pulmonary arterial compliance at baseline and over the course of treatment predicted mortality. MAIN RESULTS: Baseline pulmonary arterial compliance (hazard ratio, 1.18 per interquartile range of 1/pulmonary arterial compliance; 95% CI, 1.02-1.37; p = 0.03) and pulmonary vascular resistance (hazard ratio, 1.28 per interquartile range; 95% CI, 1.07-1.53; p = 0.006) both modestly predicted 60-day mortality. Baseline pulmonary arterial compliance remained predictive of mortality when pulmonary vascular resistance was in the normal range (p = 0.02). Between day 0 and day 3, pulmonary arterial compliance increased in acute respiratory distress syndrome survivors and remained unchanged in nonsurvivors, whereas pulmonary vascular resistance did not change in either group. The resistance-compliance product (resistance-compliance time) increased in survivors compared with nonsurvivors, suggesting improvements in right ventricular load. CONCLUSIONS: Baseline measures of pulmonary arterial compliance and pulmonary vascular resistance predict mortality in acute respiratory distress syndrome, and pulmonary arterial compliance remains predictive even when pulmonary vascular resistance is normal. Pulmonary arterial compliance and right ventricular load improve over time in acute respiratory distress syndrome survivors. Future studies should assess the impact of right ventricular protective acute respiratory distress syndrome treatment on right ventricular afterload and outcome.
Asunto(s)
Arteria Pulmonar/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Resistencia Vascular , Adulto , Anciano , Área Bajo la Curva , Presión Arterial , Adaptabilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Dificultad Respiratoria/mortalidad , Estudios Retrospectivos , Volumen Sistólico , Tasa de SupervivenciaRESUMEN
CONDENSED ABSTRACT: The factors that impact the clinical effectiveness of bare nitinol stents in claudicants with symptomatic femoropopliteal atherosclerosis are incompletely known. The authors analyzed variables that may influence stent durability and provide a benchmark for their effectiveness. Data analyzed from six studies (999 patients) included baseline noninvasive hemodynamic tests, angiographic characteristics, ultrasound defined stent patency and target lesion revascularization through 12-months. Baseline ankle-brachial index and lesion length predicted stent patency and target lesion revascularization and when combined interacted significantly to better predict outcomes. This meta-analysis provides an important comparator against which emerging therapies that treat claudicants with femoropopliteal atherosclerosis can be assessed. SUBJECT CODE: Peripheral Artery Disease BACKGROUND: The performance of bare metal nitinol stents in patients with symptomatic femoropopliteal peripheral artery disease (PAD) is not well defined. METHODS: Patient-level data from six large prospective trials sponsored by medical device manufacturers was abstracted and analyzed to identify a cohort of patients with claudication and femoropopliteal artery occlusive disease. Twelve-month binary patency and target lesion revascularization (TLR) rates were primary outcomes. Stent patency was assessed by duplex ultrasonography (DUS) and TLR was a clinically driven intervention. To characterize the effects of patient characteristics on the outcomes, meta-regression was performed via mixed effects logistic regression models with patient-level covariates. RESULTS: About 999 patients were analyzed; the mean ABI was 0.68 ± 0.18, the mean lesion length was 84 ± 53 mm, the mean lesion stenosis was 78%, and nearly two thirds of patients had mild to severe calcification. The mean Rutherford clinical category was 2.7 ± 0.6 and ranged from 2.6 to 2.8 in all studies. The 12-month patency across all studies was 69.8% and TLR rates ranged from 9.2% to 19.7%. Multivariable analysis demonstrated that baseline ABI and baseline target lesion length predicted both primary patency and TLR. Further, these two variables interacted significantly to better predict TLR outcomes when used in combination. CONCLUSION: The 12-month clinical effectiveness of bare nitinol stents to treat patients with symptomatic femoropopliteal PAD is acceptable and is impacted by clinical and lesion-specific characteristics. These data provide an important and useful benchmark to compare the clinical benefit of emerging endovascular PAD therapies. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Aleaciones , Procedimientos Endovasculares/instrumentación , Arteria Femoral , Claudicación Intermitente/terapia , Enfermedad Arterial Periférica/terapia , Arteria Poplítea , Stents , Anciano , Índice Tobillo Braquial , Ensayos Clínicos como Asunto , Procedimientos Endovasculares/efectos adversos , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Humanos , Claudicación Intermitente/diagnóstico por imagen , Claudicación Intermitente/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Diseño de Prótesis , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
In chronic feeding assays, the common agrochemical inert formulant N-methyl-2-pyrrolidone (NMP) is at least 20 times more toxic to honey bee larvae than to adults, but the underlying cause of this difference is unknown. In other taxa, NMP is primarily detoxified via a cytochrome P450 mediated pathway. Using a LC-MS method, putative cytochrome P450 metabolites of NMP were identified and quantified in adults and larvae following chronic exposure to NMP. Major differences in the identities and quantities of the generated metabolites were observed between adults and larvae. One major difference was the higher percentage of the administered NMP recovered as the parent compound in larvae compared to adults. To further explore the apparent difference in metabolic capacity, a spectrofluorometric method was used to compare general cytochrome P450 enzyme activity by monitoring the transformation of a 7-ethoxycoumarin substrate. Higher microsomal levels of 7-ethoxycoumarin-O-deethylase activity in adult fat bodies suggests that the higher percentage of unmetabolized NMP in larvae relative to adults may be due to lower cytochrome P450 enzyme activity in fat bodies. Taken together, these results suggest that larvae may be less able to detoxify xenobiotics encountered in diet than adults, and these findings will help inform future risk assessment.
Asunto(s)
Abejas/metabolismo , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Pirrolidinonas/toxicidad , Animales , Cumarinas , LarvaAsunto(s)
Hipertensión Arterial Pulmonar , Enfermedades Vasculares , Disfunción Ventricular Derecha , Biomarcadores/metabolismo , Humanos , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/metabolismo , Medición de Riesgo , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología , Enfermedades Vasculares/metabolismo , Enfermedades Vasculares/terapia , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/terapiaRESUMEN
Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental impacts of agrochemicals on non-target species such as bees. Why most formulations are more toxic to bees than respective active ingredients and how pesticides interact to cause pollinator decline cannot be answered without understanding the prevailing environmental chemical background to which bees are exposed. Modern pesticide formulations and seed treatments, particularly when multiple active ingredients are blended, require proprietary adjuvants and inert ingredients to achieve high efficacy for targeted pests. Although we have found over 130 different pesticides and metabolites in beehive samples, no individual pesticide or amount correlates with recent bee declines. Recently we have shown that honey bees are sensitive to organosilicone surfactants, nonylphenol polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co-formulants used in agrochemicals and frequent pollutants within the beehive. Effects include learning impairment for adult bees and chronic toxicity in larval feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are used and released into US environments. These synthetic organic chemicals are generally recognized as safe, have no mandated tolerances, and residues remain largely unmonitored. In contrast to finding about 70% of the pesticide active ingredients searched for in our pesticide analysis of beehive samples, we have found 100% of the other formulation ingredients targeted for analysis. These 'inerts' overwhelm the chemical burden from active pesticide, drug and personal care ingredients with which they are formulated. Honey bees serve as an optimal terrestrial bioindicator to determine if 'the formulation and not just the dose makes the poison'.
Asunto(s)
Abejas/efectos de los fármacos , Compuestos de Organosilicio/toxicidad , Plaguicidas/toxicidad , Tensoactivos/toxicidad , Animales , Abejas/fisiología , Conducta Animal/efectos de los fármacos , Compuestos de Organosilicio/química , Plaguicidas/química , Tensoactivos/químicaRESUMEN
Objective: The current study investigated procrastination as a potential moderator of the association between cannabis use and college grade point average (GPA). Participants: 220 college students (ages 18 - 24; 71.8% female) in the Northwestern U.S. who were registered for classes in Fall 2021. Methods: Demographic questions, substance use history, the Beck Anxiety Inventory, the Center for Epidemiologic Studies Depression scale, and a Procrastination scale were completed via an online survey. Official term and cumulative GPA records were also collected. Results: A regression model indicated that procrastination moderated the association between lifetime cannabis use and cumulative college GPA, whereas this moderation was not present when examining the relationship between past month cannabis use and term GPA. Conclusion: The current study identifies a putatively modifiable factor that may be related to academic performance for students who use cannabis. These results may help inform future interventions designed to help students using cannabis succeed academically.
RESUMEN
BACKGROUND: In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning. METHODS: The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia's pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first. DISCUSSION: This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05998018 , registered August 2023.