Initial experience with eversion carotid endarterectomy: Absence of a learning curve for the first 100 patients

ObjectiveEversion carotid endarterectomy (CEA) has been touted as superior to standard CEA with patch closure because of allegedly lower restenosis rates and greater technical ease of performance. The purpose of this study was to evaluate the early experience of one vascular surgeon beginning to use this technique.MethodsThis was a retrospective study in an academic vascular surgical practice. The first 100 patients undergoing CEA via the eversion technique were compared with 100 contemporaneous patients who had standard CEA with patch closure. Residual (first examination within 3 months) or recurrent postoperative duplex scan stenosis, perioperative neurologic deficit, and mortality were analyzed by cumulative sum failure and Kaplan-Meier life-table analysis.ResultsOperative indications were not significantly different between eversion and standard CEA patients (63% vs 60% asymptomatic, 10% vs 7% stroke, 4% vs 5% amaurosis, and 23% vs 28% transient ischemia). Intraoperative shunting was more commonly used during eversion CEA (87% vs 59%; P < .01). Perioperative neurologic deficits included amaurosis (n = 1) after eversion CEA and transient cerebral ischemia (n = 1) and retinal infarction (n = 1) after standard CEA, with one cardiac death each. By 36 months, one other patient in each group had experienced a transient ischemic event, but there were no strokes. Four carotids occluded within 36 months of eversion CEA, compared with one occlusion after standard CEA (not significant). Patients undergoing eversion CEA showed no difference in critical (>80%) residual or recurrent stenosis rates. However, after eversion CEA, a greater degree of greater than 50% recurrent stenosis was observed at 36 months (38% vs 6%; P < .001) despite similar residual stenosis rates. Cumulative sum failure analysis showed no plateau among patients undergoing eversion CEA, thus indicating the absence of a learning curve, at least within the first 100 patients.ConclusionsDespite enthusiasm by advocates for eversion CEA, the recurrent greater than 50% stenosis rate remained high for the first 100 patients who underwent this technique, with no evidence of a learning curve. This observation implies that vascular surgeons considering adoption of this technique should monitor their own early results carefully

Understanding and preventing injecting-related bacterial and fungal infections among people who inject drugs

Background: Injection drug use-associated bacterial and fungal infections (e.g., skin and soft tissue infections, endocarditis, osteomyelitis, septic arthritis, epidural abscess, etc.) are increasingly common. Risk factors include subcutaneous/intramuscular injecting and lack of skin cleaning, but individual-level educational interventions on safer injecting practices have shown limited effectiveness. There may be value in looking beyond individual injecting behaviours to understand risk and prevention opportunities. Aims: (1) identify social-structural factors that influence risk for injecting-related infections; (2) estimate the effect of opioid agonist treatment on all-cause mortality or infection-related rehospitalization, after hospital admissions with injecting-related infections; (3) assess how risk for injecting-related infections changes within-individuals over time, in relation to social (i.e., incarceration) and clinical (i.e., opioid agonist treatment) exposures. Methods: Qualitative systematic review with thematic synthesis; quantitative systematic review with meta-analysis; survival analysis and self-controlled case series using data from a cohort of people with opioid use disorder in New South Wales, Australia. Results: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services, and harmful health care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community. After a hospital admission, opioid agonist treatment is associated with a large reduction in mortality but a modest reduction in risk of infection-related rehospitalization. Risk of injecting-related infections changes substantially within-individuals over time; high-risk moments include release from incarceration and around initiation and discontinuation of opioid agonist treatment. Conclusions: Risk for injecting-related bacterial and fungal infections, and associated treatment outcomes, are shaped by social-structural factors beyond individuals’ control. Offering individual-level education and addiction treatment may be helpful, but is likely insufficient. Prevention and treatment strategies should engage more broadly with the social and material conditions within which people prepare and consume drugs, and access health car

Association between drug poisoning deaths and season, week, weekday, and public holidays: protocol for a time series analysis of daily counts in England and Wales, 1993-2018

The number of deaths due to drug poisoning in England and Wales is increasing rapidly. Annual data shows that deaths plateaued in the decade before 2011 and then sharply increased. To improve our understanding of this problem and identify potential opportunities to prioritise harm reduction and addiction treatment services, we will investigate within-year and cyclical variation in deaths. This is a protocol for a time series analysis to assess whether risk of drug-related varies by season, by week of the month, by day of the week, and at public holidays. These trends have not been widely studied. The results could contribute to our understanding of environmental drivers of death due to drug poisoning, and to the planning of public health and clinical services that aim to prevent drug-related deaths

Morphology of the Planum Boreum basal unit, Mars, and constraints on the origin and timing of icy circumpolar deposits

textData from the Shallow Radar instrument on Mars Reconnaissance Orbiter have enabled detailed scientific exploration of martian ice. Orbital ground penetrating radar enabled scientists to study subsurface ice stratigraphy, to uncover the geologic structure of ice on Mars with remarkable results for the north pole. On the north pole of Mars sits a massive, approximately two kilometer thick, deposit of pure water ice. This deposit is underlain with a sand and ice mixture that reaches 1.5 km maximum thickness. This dissertation examines the nature of the old sand/ice mixture on Mars' north pole. We use this ice to identify early trends in deposition and erosion on Mars' north pole and ultimately to link ice rich deposits that are not part of the polar cap. This multi-part study endeavors to understand and constrain the drivers of Mars' polar ice deposition. With careful stratigraphic analysis we hypothesize that depositional regime has not changed drastically since the upper part of the sand and ice mixture was emplaced in Middle Amazonian time. Sediment supply became limited and ice more plentiful with respect to sand; however, deposition remained aeolian in nature. Additionally, our work finds evidence that circumpolar landforms are related to the central mass of ice on Planum Boreum. We present evidence supporting a coeval evolution of the circumpolar deposits and central Planum Boreum. We also present evidence that refutes these features being part of a more extensive ancient ice cap. This indicates that the processes occurring at Planum Boreum are likely mirrored in nearby landforms such as small craters and isolated ice wedges. This is fundamental to polar science, the processes occurring on Planum Boreum and the processes responsible for deposition of the north polar layered deposits can be analyzed at additional locations. Furthermore, we find that if a climate signal exists in the ice deposits, as has been postulated, these circumpolar features are likely to contain the same climate signal as the central ice cap. Thus, this work unifies the complexity of martian polar processes and suggests future avenues of research.Geological Science

Health-care resource use among patients who use illicit opioids in England, 2010–20: A descriptive matched cohort study

Background and aims: People who use illicit opioids have higher mortality and morbidity than the general population. Limited quantitative research has investigated how this population engages with health-care, particularly regarding planned and primary care. We aimed to measure health-care use among patients with a history of illicit opioid use in England across five settings: general practice (GP), hospital outpatient care, emergency departments, emergency hospital admissions and elective hospital admissions. // Design: This was a matched cohort study using Clinical Practice Research Datalink and Hospital Episode Statistics. // Setting: Primary and secondary care practices in England took part in the study. // Participants: A total of 57 421 patients with a history of illicit opioid use were identified by GPs between 2010 and 2020, and 172 263 patients with no recorded history of illicit opioid use matched by age, sex and practice. // Measurements: We estimated the rate (events per unit of time) of attendance and used quasi-Poisson regression (unadjusted and adjusted) to estimate rate ratios between groups. We also compared rates of planned and unplanned hospital admissions for diagnoses and calculated excess admissions and rate ratios between groups. // Findings: A history of using illicit opioids was associated with higher rates of health-care use in all settings. Rate ratios for those with a history of using illicit opioids relative to those without were 2.38 [95% confidence interval (CI) = 2.36–2.41] for GP; 1.99 (95% CI = 1.94–2.03) for hospital outpatient visits; 2.80 (95% CI = 2.73–2.87) for emergency department visits; 4.98 (95% CI = 4.82–5.14) for emergency hospital admissions; and 1.76 (95% CI = 1.60–1.94) for elective hospital admissions. For emergency hospital admissions, diagnoses with the most excess admissions were drug-related and respiratory conditions, and those with the highest rate ratios were personality and behaviour (25.5, 95% CI = 23.5–27.6), drug-related (21.2, 95% CI = 20.1–21.6) and chronic obstructive pulmonary disease (19.4, 95% CI = 18.7–20.2). // Conclusions: Patients who use illicit opioids in England appear to access health services more often than people of the same age and sex who do not use illicit opioids among a wide range of health-care settings. The difference is especially large for emergency care, which probably reflects both episodic illness and decompensation of long-term conditions

Preoperative thromboxane A2/prostaglandin H2 receptor activity predicts early graft thrombosis

AbstractPurpose: This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expression of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. A prospective correlation of preoperative platelet TXA2/PGH2 receptor-mediated activity with lower extremity graft patency was sought. Methods: Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome measures were primary graft patency rate at 3 months, platelet TXA2/PGH2 receptor activity by equilibrium binding with 125I-BOP, and aggregation to the TXA2-mimetic U46619. Results: Preoperative platelet TXA2/PGH2 receptor density was higher (Bmax, 3100 ± 1300 vs 1500 ± 1100 sites/platelet [mean ± SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 was lower (26 ± 6 nmol/L vs 57 ± 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased receptor density. Early graft thrombosis was more likely in patients with a platelet TXA2/PGH2 receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180). Conclusions: Elevated platelet TXA2/PGH2 receptor levels and enhanced sensitivity of platelet aggregation to TXA2 predict early arterial graft thrombosis. Specific TXA2/PGH2 receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion. (J Vasc Surg 1998;27:317-28.

Bypass and embolization for a vertebral artery aneurysm in a patient with Marfan syndrome

Extracranial vertebral artery aneurysms represent an uncommon presentation of collagen vascular disease. We performed staged proximal embolization of large left vertebral artery aneurysm after distal common carotid-to-vertebral bypass at C2 in a young adult patient with Marfan syndrome and a hypoplastic contralateral vertebral artery. Dilation of the autogenous saphenous vein graft occurred at 1 year with proximal graft stenosis requiring operative revision. Subsequent dilation of the basilar artery led to symptoms of pontine compression at 18 months that have resolved at 31 months of follow-up

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Opioid Injection-Associated Bacterial Infections in England, 2002–2021: A Time Series Analysis of Seasonal Variation and the Impact of Coronavirus Disease 2019

BACKGROUND: Bacterial infections cause substantial pain and disability among people who inject drugs. We described time trends in hospital admissions for injecting-related infections in England. METHODS: We analyzed hospital admissions in England between January 2002 and December 2021. We included patients with infections commonly caused by drug injection, including cutaneous abscesses, cellulitis, endocarditis, or osteomyelitis, and a diagnosis of opioid use disorder. We used Poisson regression to estimate seasonal variation and changes associated with coronavirus disease 2019 (COVID-19) response. RESULTS: There were 92 303 hospital admissions for injection-associated infections between 2002 and 2021. Eighty-seven percent were skin, soft-tissue, or vascular infections; 72% of patients were male; and the median age increased from 31 years in 2002 to 42 years in 2021. The rate of admissions reduced from 13.97 per day (95% confidence interval [CI], 13.59-14.36) in 2003 to 8.94 (95% CI, 8.64-9.25) in 2011, then increased to 18.91 (95% CI, 18.46-19.36) in 2019. At the introduction of COVID-19 response in March 2020, the rate of injection-associated infections reduced by 35.3% (95% CI, 32.1-38.4). Injection-associated infections were also seasonal; the rate was 1.21 (95% CI, 1.18-1.24) times higher in July than in February. CONCLUSIONS: This incidence of opioid injection-associated infections varies within years and reduced following COVID-19 response measures. This suggests that social and structural factors such as housing and the degree of social mixing may contribute to the risk of infection, supporting investment in improved social conditions for this population as a means to reduce the burden of injecting-related infections

Empirical Correspondence Between Trophic Transfer Efficiency in Freshwater Food Webs and the Slope of Their Size Spectra

The density of organisms declines with size, because larger organisms need more energy than smaller ones and energetic losses occur when larger organisms feed on smaller ones. A potential expression of density-size distributions are Normalized Biomass Size Spectra (NBSS), which plot the logarithm of biomass independent of taxonomy within bins of logarithmic organismal size, divided by the bin width. Theoretically, the NBSS slope of multi-trophic communities is exactly 1.0 if the trophic transfer efficiency (TTE, ratio of production rates between adjacent trophic levels) is 10% and the predator-prey mass ratio (PPMR) is fixed at 104 . Here we provide evidence from four multi-trophic lake food webs that empirically estimated TTEs correspond to empirically estimated slopes of the respective community NBSS. Each of the NBSS considered pelagic and benthic organisms spanning size ranges from bacteria to fish, all sampled over three seasons in 1 yr. The four NBSS slopes were significantly steeper than 1.0 (range 1.14 to 1.19, with 95% CIs excluding 1). The corresponding average TTEs were substantially lower than 10% in each of the four food webs (range 1.0% to 3.6%, mean 1.85%). The overall slope merging all biomass-size data pairs from the four systems (1.17) was almost identical to the slope predicted from the arithmetic mean TTE of the four food webs (1.18) assuming a constant PPMR of 104 . Accordingly, our empirical data confirm the theoretically predicted quantitative relationship between TTE and the slope of the biomass-size distribution. Furthermore, we show that benthic and pelagic organisms can be merged into a community NBSS, but future studies have yet to explore potential differences in habitat-specific TTEs and PPMRs. We suggest that community NBSS may provide valuable information on the structure of food webs and their energetic pathways, and can result in improved accuracy of TTE-estimates