Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Clinical and in vitro evaluation of new anti-redness cosmetic products in subjects with winter xerosis and sensitive skin.

OBJECTIVE: To demonstrate the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determine the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti-redness (AR) formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin. METHODS: The anti-inflammatory and skin protective properties of panthenol, PEA and NAM were evaluated in vitro. The physical properties of the AR formulations were analysed using measurement of water vapour transport rate (WVTR) and infrared spectroscopy. Clinical studies were performed between the months of December and April (2014-2015) with efficacy assessed during the winter. Facial redness, irritation, sensitization potential, photo-irritation, and photo-sensitization were evaluated. Self-assessed adverse reactions were reported in diaries of use. RESULTS: Panthenol and PEA reduced prostaglandin E2 , interleukin-6, and thymic stromal lymphopoietin levels in vitro, while NAM induced nicotinamide adenine dinucleotide (NAD) levels and the keratinocyte differentiation markers: filaggrin (2-fold increase, P < 0.001), loricrin (2-fold increase, P < 0.05), involucrin (2 fold increase, P < 0.001) & peroxisomal proliferator activated receptor-alpha (1.5 fold increase, P < 0.05). The two AR products exhibited low WVTR vs. no treatment (P < 0.001) and displayed an ordered lipid structure. The day cream formulation protected against ultraviolet B radiation in vitro. A total of 382 participants were included in clinical studies which showed the AR formulations significantly improved facial redness associated with winter xerosis (Day 29 mean change from baseline: AR day cream 0.77 (P < 0.001); AR serum 0.67 (P < 0.001)). No irritation, sensitization, photo-irritation, photo-sensitization or product-related adverse reactions were observed or reported in the clinical studies. CONCLUSION: The new products significantly improved skin redness associated with winter xerosis in participants with self-perceived sensitive skin. Both products were well tolerated with a suitable safety profile for topical use in subjects with sensitive skin.

OBJECTIF: Démontrer l'activité in vitro du panthénol, du palmitoyléthanolamide (PEA), et du nicotinamide (NAM) et déterminer les propriétés biophysiques, la sécurité clinique, la tolérance ainsi que l'efficacité de deux formulations anti-rougeurs (AR) en développement contenant ces ingrédients pour atténuer les rougeurs faciales associées à la xérose hivernale chez des volontaires sains présentant une peau sensible. MÉTHODES: Les propriétés anti-inflammatoires et protectrices du panthénol, du PEA et du NAM ont été évaluées in vitro. Les propriétés physiques des formulations AR ont été analysées en mesurant le taux de transport de vapeur d'eau (WVTR) et par spectroscopie infrarouge. Des études cliniques ont été réalisées entre décembre et avril (2014-2015) et l'efficacité a été évaluée pendant l'hiver. Les rougeurs, l'irritation, le potentiel de sensibilisation, la photo-irritation et la photosensibilisation au niveau du visage ont été évalués. Des effets indésirables auto-évalués ont été signalés dans des journaux d'utilisation. RÉSULTATS: Le panthénol et le PEA ont réduit les niveaux de prostaglandine E2 , d'interleukine-6 et de lymphopoiétine stromale thymique in vitro, tandis que le NAM a généré une augmentation des taux de nicotinamide adénine dinucléotide (NAD) et des marqueurs de différenciation kératinocytaire : filaggrine (multiplication des taux par 2, P < 0,001), loricrine (multiplication des taux par 2, P < 0,05), involucrine (multiplication des taux par 2, P < 0,001) et du récepteur alpha activé de la prolifération peroxysomale (multiplication des taux par 1,5, P < 0,05). Les deux produits antirétroviraux présentaient un faible taux de WVTR par rapport à l'absence de traitement (P < 0,001) et présentaient une structure lipidique ordonnée. La formulation de la crème de jour protège contre le rayonnement ultraviolet B in vitro. Un total de 382 participants ont été inclus dans les études cliniques qui ont montré que les formulations AR amélioraient significativement les rougeurs faciales associées à la xérose hivernale (changement moyen du jour 29 par rapport à la référence : crème de jour AR 0,77 (P < 0,001) ; sérum AR 0,67 (P < 0,001)). Aucune irritation, sensibilisation, photo-irritation, photosensibilisation ni effet indésirable lié au produit n'a été observé ou signalé dans les études cliniques. CONCLUSION: Les nouveaux produits ont considérablement amélioré la rougeur de la peau associée à la xérose hivernale chez les participants présentant une peau sensible auto-perçue. Les deux produits ont été bien tolérés avec un profil de sécurité approprié pour un usage topique chez les sujets présentant une peau sensible.

Physiological and Biomechanical Mechanisms of Distance Specific Human Running Performance.

SYNOPSIS: Running events range from 60-m sprints to ultra-marathons covering 100 miles or more, which presents an interesting diversity in terms of the parameters for successful performance. Here, we review the physiological and biomechanical variations underlying elite human running performance in sprint to ultramarathon distances. Maximal running speeds observed in sprint disciplines are achieved by high vertical ground reaction forces applied over short contact times. To create this high force output, sprint events rely heavily on anaerobic metabolism, as well as a high number and large cross-sectional area of type II fibers in the leg muscles. Middle distance running performance is characterized by intermediates of biomechanical and physiological parameters, with the possibility of unique combinations of each leading to high-level performance. The relatively fast velocities in mid-distance events require a high mechanical power output, though ground reaction forces are less than in sprinting. Elite mid-distance runners exhibit local muscle adaptations that, along with a large anaerobic capacity, provide the ability to generate a high power output. Aerobic capacity starts to become an important aspect of performance in middle distance events, especially as distance increases. In distance running events, V˙O2max is an important determinant of performance, but is relatively homogeneous in elite runners. V˙O2 and velocity at lactate threshold have been shown to be superior predictors of elite distance running performance. Ultramarathons are relatively new running events, as such, less is known about physiological and biomechanical parameters that underlie ultra-marathon performance. However, it is clear that performance in these events is related to aerobic capacity, fuel utilization, and fatigue resistance.

Superficial plantar cutaneous sensation does not trigger barefoot running adaptations.

It has long been proposed that the gait alterations associated with barefoot running are mediated by alterations in sensory feedback, yet there has been no data to support this claim. Thus, the purpose of this study was to examine the role of superficial plantar cutaneous feedback in barefoot and shod running. METHODS: 10 healthy active subjects (6 male, 4 female); mass: 65.2+9.7kg; age: 27+7.1years participated in this study. 10 over-ground running trials were completed in each of the following conditions: barefoot (BF), shod (SHOD), anesthetized barefoot (ANEST BF) and anesthetized shod (ANEST SHOD). For the anesthetized conditions 0.1-0.3mL of 1% lidocaine was injected into the dermal layer of the plantar foot below the metatarsal heads, lateral column and heel. 3-dimensional motion analysis and ground reaction force (GRF) data were captured as subjects ran over a 20m runway with a force plate at 12m. Kinematic and kinetic differences were analyzed via two-way repeated measure ANOVAs. RESULTS: The differences in gait between the BF and SHOD conditions were consistent with previous research, with subjects exhibiting a significant decrease in stride length and changing from rearfoot strike when SHOD to fore/midfoot strike when BF. Additionally, BF running was associated with decreased impact peak magnitudes and peak vertical GRFs. Despite anesthetizing the plantar surface, there was no difference between the BF and ANEST BF conditions in terms of stride length, foot strike or GRFs. CONCLUSION: Superficial cutaneous sensory receptors are not primarily responsible for the gait changes associated with barefoot running.

Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib.

This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1-7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (⩾PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%.

Kinematic and kinetic comparison of barefoot and shod running in mid/forefoot and rearfoot strike runners.

Barefoot running has been associated with decreased stride length and switching from a rearfoot strike (RFS) pattern to a mid/forefoot strike (M/FFS) pattern. However, some individuals naturally contact the ground on their mid/forefoot, even when wearing cushioned running shoes. The purpose of this study was to determine if the mechanics of barefoot running by natural shod RFS runners differed from natural shod M/FFS runners. Twenty habitually shod runners (ten natural M/FFS and ten natural RFS) participated in this study. Three-dimensional motion analysis and ground reaction force data were captured as subjects ran at their preferred running speed in both barefoot and shod conditions. M/FFS experienced only a decrease in stride length when switching from shod to barefoot running. Whereas, when switching from shod to barefoot running, RFS individuals experienced a decrease in stride length, switched to a plantarflexed position at ground contact and saw reduced impact peak magnitudes. These results suggest that when barefoot, the RFS group ran similar to the M/FFS group running barefoot or shod.

The effect of stride length on the dynamics of barefoot and shod running.

A number of interventions and technique changes have been proposed to attempt to improve performance and reduce the number of running related injuries. Running shoes, barefoot running and alterations in spatio-temporal parameters (stride frequency and stride length) have been associated with significant kinematic and kinetic changes, which may have implications for performance and injury prevention. However, because footwear interventions have been shown to also affect spatio-temporal parameters, there is uncertainty regarding the origin of the kinematic and kinetic alterations. Therefore, the purpose of this study was to independently evaluate the effects of shoes and changes in stride length on lower extremity kinetics. Eleven individuals ran over-ground at stride lengths ± 5 and 10% of their preferred stride length, in both the barefoot and shod condition. Three-dimensional motion capture and force plate data were captured synchronously and used to compute lower extremity joint moments. We found a significant main effect of stride length on anterior-posterior and vertical GRFs, and sagittal plane knee and ankle moments in both barefoot and shod running. When subjects ran at identical stride lengths in the barefoot and shod conditions we did not observe differences for any of the kinetic variables that were measured. These findings suggest that barefoot running triggers a decrease in stride length, which could lead to a decrease in GRFs and sagittal plane joint moments. When evaluating barefoot running as a potential option to reduce injury, it is important to consider the associated change in stride length.

What liver transplant outcomes can be expected in the uninsured who become insured via the Affordable Care Act?

Our study objective is to measure the survival impact of insurance status following liver transplantation in a cohort of uninsured "charity care" patients. These patients are analogous to the population who will gain insurance via the Affordable Care Act. We hypothesize there will be reduced survival in charity care compared to other insurance strata. We conducted a retrospective study of 898 liver transplants from 2000 to 2010. Insurance cohorts were classified as private (n = 640), public (n = 233) and charity care (n = 23). The 1, 3 and 5-year survival was 92%, 88% and 83% in private insurance, 89%, 80% and 73% in public insurance and 83%, 72% and 51% in charity care. Compared to private insurance, multivariable regression analyses demonstrated charity care (HR 3.11, CI 1.41-6.86) and public insurance (HR 1.58, CI 1.06-2.34) had a higher 5-year mortality hazard ratio. In contrast, other measures of socioeconomic status were not significantly associated with increased mortality. The charity care cohort demonstrated the highest incidence of acute rejection and missed clinic appointments. These data suggest factors other than demographic and socioeconomic may be associated with increased mortality. Further investigations are necessary to determine causative predictors of increased mortality in liver transplant patients without private insurance.

The PREGVAXGRIP study: a cohort study to assess foetal and neonatal consequences of in utero exposure to vaccination against A(H1N1)v2009 influenza.

BACKGROUND: In October 2009, in the context of an A(H1N1)v2009 influenza pandemic, a vaccination campaign was launched in France, in which one of the priority groups was pregnant women, on account of the high risk of developing complications following infection by this virus. OBJECTIVE: The aim of this multicentric, prospective, observational study was to assess safety and pregnancy outcomes in a cohort of pregnant women when receiving the A(H1N1)v2009 influenza pandemic vaccine. METHODS: This was a prospective study that followed up pregnant women recruited mainly in vaccination centres and maternity departments. Following the expected delivery date, follow-up data were collected concerning the delivery, the infant, and, if appropriate, the reasons why the pregnancy did not reach its term. RESULTS: Between 1 November 2009 and 31 March 2010, 2,415 pregnant women were included at the time of vaccination; 97.6 % of women received a vaccine without adjuvant and 2.4 % received an adjuvanted vaccine. Ninety-two (3.9 %) women were vaccinated during the first trimester of pregnancy, 1,090 (46.5 %) during the second trimester, and 1,162 (49.6 %) during the third trimester. One hundred and thirty-three adverse events (5.5 % of women) were reported, of which 12 were unexpected or serious. There were 2,246 (93.0 %) known pregnancy outcomes with 12 spontaneous abortions (0.5 %), 6 stillbirths (0.3 %), and 4 therapeutic abortions (0.2 %). There were 65 neonates with congenital anomalies, among which 31 were major. But only one congenital malformation (1.4 %) was reported for the 92 women vaccinated in their first trimester. Of the women, 93.3 % were delivered full term and 6.7 % preterm. For 96 (4.2 %) neonates, a disorder was reported in the neonatal period and 130 (5.6 %) were transferred to the neonatology department. CONCLUSIONS: This study suggests that exposure to the A(H1N1)v2009 pandemic influenza vaccine during pregnancy does not increase the risk of adverse pregnancy outcomes. However, because of the relatively small number of women exposed during the first trimester, other studies are needed to exclude an increased risk of malformation.

Continuation of pregnancy after first-trimester exposure to mifepristone: an observational prospective study.

OBJECTIVE: To report the follow-up of continuing pregnancies after first-trimester exposure to mifepristone. DESIGN: Observational prospective study. SETTING: France. SAMPLE: Patients exposed to mifepristone during the first 12 weeks of pregnancy. METHODS: Women were included in the study when they or their doctors asked a French pharmacovigilance centre or the Paris Teratogen Information Service about the risk of mifepristone exposure in early pregnancy. Exclusion criteria were requests received after 22 weeks of gestation or subsequent elective termination of pregnancy without a pathological examination of the fetus. Data on maternal history and drug exposure were collected on first contact, and pregnancy outcomes were documented at follow-up. MAIN OUTCOME MEASURES: Rate of major congenital malformations. RESULTS: A total of 105 pregnancies were included, with 46 exposed to mifepristone alone, and 59 exposed to both mifepristone and misoprostol. There were 94 live births (90.4%) and 10 (9.6%) miscarriages (including one with major malformation). Elective termination of pregnancy was performed after the subsequent diagnosis of trisomy 21 in one case. The overall rate of major congenital malformations was 4.2% (95% CI 1.2-10.4%), with two cases among 38 patients exposed to mifepristone alone, and two cases among 57 patients exposed to both mifepristone and misoprostol. CONCLUSIONS: This first prospective study found that the rate of major malformations after first-trimester exposure to mifepristone is only slightly higher than the expected 2-3% rate in the general population. Such findings provide reassuring data for risk evaluation for continuation of pregnancy after mifepristone exposure.

Caveolae and propofol effects on airway smooth muscle.

BACKGROUND: The i.v. anaesthetic propofol produces bronchodilatation. Airway relaxation involves reduced intracellular Ca(2+) ([Ca(2+)](i)) in airway smooth muscle (ASM) and lipid rafts (caveolae), and constitutional caveolin proteins regulate [Ca(2+)](i). We postulated that propofol-induced bronchodilatation involves caveolar disruption. METHODS: Caveolar fractions of human ASM cells were tested for propofol content. [Ca(2+)](i) responses of ASM cells loaded with fura-2 were performed in the presence of 10 µM histamine with and without clinically relevant concentrations of propofol (10 and 30 µM and intralipid control). Effects on sarcoplasmic reticulum (SR) Ca(2+) release were evaluated in zero extracellular Ca(2+) using the blockers Xestospongin C and ryanodine. Store-operated Ca(2+) entry (SOCE) after SR depletion was evaluated using established techniques. The role of caveolin-1 in the effect of propofol was tested using small interference RNA (siRNA) suppression. Changes in intracellular signalling cascades relevant to [Ca(2+)](i) and force regulation were also evaluated. RESULTS: Propofol was present in ASM caveolar fractions in substantial concentrations. Exposure to 10 or 30 µM propofol form decreased [Ca(2+)](i) peak (but not plateau) responses to histamine by ~40%, an effect persistent in zero extracellular Ca(2+). Propofol effects were absent in caveolin-1 siRNA-transfected cells. Inhibition of ryanodine receptors prevented propofol effects on [Ca(2+)](i), while propofol blunted [Ca(2+)](i) responses to caffeine. Propofol reduced SOCE, an effect also prevented by caveolin-1 siRNA. Propofol effects were associated with decreased caveolin-1 expression and extracellular signal-regulated kinase phosphorylation. CONCLUSIONS: These novel data suggest a role for caveolae (specifically caveolin-1) in propofol-induced bronchodilatation. Due to its lipid nature, propofol may transiently disrupt caveolar regulation, thus altering ASM [Ca(2+)](i).

Changes in the BODE index, exacerbation duration and hospitalisation in a cohort of COPD patients.

INTRODUCTION: We investigated the relationship between frequency of exacerbation and duration and change in functional status, as measured by the BODE index in chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a longitudinal cohort study of 56 patients with moderate to severe COPD. Body mass index, spirometry, Modified Medical Research Council (MMRC) dyspnoea score and six-minute walk distance (6MWD) were measured annually when the patients were clinically stable. Data on frequency and duration of COPD exacerbations occurring in the community and requiring hospitalisation were collected prospectively. Early stage exacerbations were identified through the use of individualised patient action plans and further reinforced by fortnightly phone contact. RESULTS: At the two-year follow-up, the BODE index increased in 33 patients, remained stable in 18 and decreased in five patients. Patients with increased BODE index had significantly higher hospital presentation rates and longer total bed-days compared to those with stable BODE index. Among the 33 patients with increased BODE index, 20 had lower 6MWD and higher MMRC scores, indicating deteriorating functional status, and 13 had higher levels of airway obstruction. Between these two subgroups, patients with deteriorating functional status had higher exacerbation frequency, longer exacerbation duration and higher inpatient bed-days. Linear regression showed that total annual duration of exacerbation was predictive of change in 6MWD. CONCLUSION: Change in the BODE index is a sensitive measure of deteriorating functional status in COPD patients. Duration of exacerbation has greater impact on functional status than frequency of exacerbation episodes.

Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis.

Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing-remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment. Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN.

Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion oncoprotein.

The t(8;21) chromosomal translocation that generates the fusion oncoprotein RUNX1-ETO predominates in leukemia patients of the French-American-British (FAB) class M2 subtype. The oncoprotein has the capacity to promote expansion of hematopoietic stem/progenitor cells and induces leukemia in association with other genetic alterations. Here, we show that RUNX1-ETO undergoes degradation in response to treatment with histone deacetylase inhibitors, one of which, depsipeptide (DEP), is currently undergoing phase II clinical testing in a variety of malignancies. These compounds induce turnover of RUNX1-ETO without affecting the stability of RUNX1-ETO partner proteins. In addition, RUNX1-ETO physically interacts with heat shock protein 90 (HSP90). DEP treatment interrupts the association of RUNX1-ETO with HSP90 and induces proteasomal degradation of RUNX1-ETO. DEP and the HSP90 antagonist 17-allylamino-geldanamycin (17-AAG) both triggered RUNX1-ETO degradation, but without any additive or cooperative effects. These findings may stimulate the development of more rational and effective approaches for treating t(8;21) patients using histone deacetylase inhibitors or HSP90 inhibitors.

Lithographically patterned nanowire electrodeposition.

Nanowire fabrication methods can be classified either as 'top down', involving photo- or electron-beam lithography, or 'bottom up', involving the synthesis of nanowires from molecular precursors. Lithographically patterned nanowire electrodeposition (LPNE) combines attributes of photolithography with the versatility of bottom-up electrochemical synthesis. Photolithography defines the position of a sacrificial nickel nanoband electrode, which is recessed into a horizontal trench. This trench acts as a 'nanoform' to define the thickness of an incipient nanowire during its electrodeposition. The electrodeposition duration determines the width of the nanowire. Removal of the photoresist and nickel exposes a polycrystalline nanowire--composed of gold, platinum or palladium--characterized by thickness and width that can be independently controlled down to 18 and 40 nm, respectively. Metal nanowires prepared by LPNE may have applications in chemical sensing and optical signal processing, and as interconnects in nanoelectronic devices.

Shrinking nanowires by kinetically controlled electrooxidation.

Nanowires composed of antimony, gold, and bismuth telluride (Bi2Te3) were reduced in diameter by electrooxidation in aqueous solutions. When electrooxidation was carried out using low current densities (Jox < 150 microA cm(-2)), the mean wire diameter decreased in direct proportion to the oxidation time, as expected for a kinetically controlled process. Under these conditions, the diameter uniformity of nanowires remained constant as wires were shrunk from initial diameters of more than 120 nm to less than 40 nm, for Sb and Bi2Te3, and less than 60 nm for Au. Oxidized nanowires remained continuous for more than 100 microm. Electrooxidation at higher current densities rapidly introduced breaks into these nanowires. Electrochemical wire growth and shrinking by electrooxidation were integrated into a single electrochemical experiment that allowed the final mean diameter of nanowires to be specified with a precision of 5-10 nm.

A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity.

OBJECTIVES: To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV. STUDY DESIGN: An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL. METHODS: Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions. RESULTS: The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms. CONCLUSIONS: Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.