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Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability. Methods/Design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention. Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.
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Bacteriophage Curie is a podovirus that infects Microbacterium foliorum. The Curie genome spans 16,810 bp, has 90 bp terminal inverted repeats, and includes 23 protein-coding genes. Its genome architecture resembles phage PineapplePizza and other phi29-like phages. Together, Curie and PineapplePizza form a new actinobacteriophage Cluster GI.
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Copepods of the genus Calanus dominate the biomass of pelagic ecosystems from the Mediterranean Sea up into the Arctic Ocean and form an important link between phytoplankton and higher trophic levels. Impacts from toxin-producing harmful algae (HA) have been recorded throughout this region over the last 50 years, with potentially negative effects on Calanus spp. populations and the ecosystem functions and services they provide. Here we examine how ingestion, egg-production and egg-viability in Calanus helgolandicus are affected by the relative abundance of the toxin-producing dinoflagellate Alexandrium catenella in their diet. Our four-day experiments demonstrate that the ingestion rate of C. helgolandicus declined significantly as the percentage of toxin-producing A. catenella within their diet increased, whereas egg production and egg viability were unaffected. Toxin profile concentrations for A. catenella are presented alongside body toxin-loads in C. helgolandicus after 4 days of feeding on these cells. The body toxin concentrations of C. helgolandicus were 3.6-356.6 pg STX diHCl eq. copepod-1, approximately 0.02-3.3 % of the toxins ingested. Our work suggests that the effects of exposure to A. catenella may be negligible in the short-term but could manifest if bloom conditions persist for longer than our experimental duration.
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Copépodes , Dinoflagellida , Animais , Ecossistema , Toxinas Marinhas , ReproduçãoRESUMO
PURPOSE: PREF-NET reported patients' experience of Somatuline® (lanreotide) Autogel® (LAN) administration at home and in hospital among patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). METHODS: PREF-NET was a multicentre, cross-sectional study of UK adults (aged ≥ 18 years) with GEP-NETs receiving a stable dose of LAN, which comprised of (1) a quantitative online survey, and (2) qualitative semi-structured interviews conducted with a subgroup of survey respondents. The primary objective was the description of overall patient preference for home versus hospital administration of LAN. Secondary objectives included describing patient-reported opinions on the experience and associated preference for each administration setting, and the impact on healthcare utilisation, societal cost, activities of daily living and health-related quality of life (HRQoL). RESULTS: In the primary analysis (80 patients; mean age 63.9 years), 98.7% (95% confidence interval [CI]: 96.1-100.0) of patients preferred to receive LAN at home, compared with 1.3% (95% CI: 0.0-3.9) who preferred the hospital setting. Among participants, over half (60.3%) received their injection from a non-healthcare professional. Most patients (79.5% [95% CI: 70.5-88.4]) reported a positive effect on HRQoL after the switch from hospital to home administration. Qualitative interviews (20 patients; mean age 63.6 years) highlighted that patients preferred home administration because it improved overall convenience; saved time and costs; made them feel more comfortable and relaxed, and less stressed; and increased confidence in their ability to self-manage their treatment. CONCLUSION: Almost all patients preferred to receive LAN treatment at home rather than in hospital with increased convenience and psychological benefits reported as key reasons for this preference.
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Atividades Cotidianas , Tumores Neuroendócrinos , Peptídeos Cíclicos , Somatostatina/análogos & derivados , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Tumores Neuroendócrinos/tratamento farmacológico , Preferência do Paciente , Qualidade de Vida , Hospitais , Reino UnidoRESUMO
Using the socio-ecological model, this qualitative study aimed to explore teachers' perspectives on the barriers and facilitators to Fundamental Movement Skills (FMS) and physical activity engagement in children living in deprived areas in the UK. A purposive sample of 14 primary school teachers participated in semi-structured focus groups drawn from schools situated in lower SES wards and ethnically diverse areas in Central England. Thematic analysis of transcripts identified multiple and interrelated factors across all levels of the socio-ecological model for barriers to FMS and PA (i.e., intrapersonal, interpersonal, organisational, community and policy). Facilitators at three levels of influence were found (i.e., intrapersonal, interpersonal and organisational). We conclude, barriers and enablers to the PA and FMS in children from ethnically diverse backgrounds living in deprived areas are multifactorial and interrelated. At a school level, initiatives to increase PA and develop the FMS needed to be active are likely to be ineffective unless the barriers are addressed at all levels and considered more holistically with their complexity. Multi-disciplinary solutions are needed across sectors given the range of complex and interrelated factors.
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Exercício Físico , Instituições Acadêmicas , Criança , Humanos , Pesquisa Qualitativa , Professores Escolares , Reino UnidoRESUMO
The changing Arctic environment is affecting zooplankton that support its abundant wildlife. We examined how these changes are influencing a key zooplankton species, Calanus finmarchicus, principally found in the North Atlantic but expatriated to the Arctic. Close to the ice-edge in the Fram Strait, we identified areas that, since the 1980s, are increasingly favourable to C. finmarchicus. Field-sampling revealed part of the population there to be capable of amassing enough reserves to overwinter. Early developmental stages were also present in early summer, suggesting successful local recruitment. This extension to suitable C. finmarchicus habitat is most likely facilitated by the long-term retreat of the ice-edge, allowing phytoplankton to bloom earlier and for longer and through higher temperatures increasing copepod developmental rates. The increased capacity for this species to complete its life-cycle and prosper in the Fram Strait can change community structure, with large consequences to regional food-webs.
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Copépodes , Animais , Regiões Árticas , Ecossistema , Cadeia Alimentar , ZooplânctonRESUMO
ABSTRACT: Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients.This multisite study focused on patients (≥65âyears of age) on a ketogenic diet. Medical records were identified with the keywords "keto," "ketogenic," and "Atkins." Records were reviewed in detail with extraction of direct quotations to substantiate observations.We report on 200 consecutive patients with a median age of 70âyears. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1âmonth. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight ("She has lost 15 pounds and plans to lose another 8"); 36 of 67 (54%) who sought glucose control appeared to achieve the latter ("He has gone on a ketogenic diet and has been able to bring his sugars down significantly"); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them ("He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet"). Adverse events occurred in 30 patients (15%): dyslipidemia (nâ=â14), constipation (nâ=â9), sub-therapeutic international normalized ratio (nâ=â3), pancreatitis (nâ=â2), diarrhea (nâ=â1), and fatigue (nâ=â1).Trials that test ketogenic diets for a variety of illnesses should enroll older adults.
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Dieta Cetogênica , Obesidade/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Fadiga , Feminino , Humanos , Masculino , Neoplasias/terapia , Qualidade de Vida , Redução de PesoRESUMO
PURPOSE: This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients' decision making on trial enrollment. METHODS: This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making. RESULTS: In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: "The information in this consent form helped me make a decision about whether or not to enroll in the trial" (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign. CONCLUSION: This study's primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.
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COVID-19 , Neoplasias , Adulto , Termos de Consentimento , Método Duplo-Cego , Humanos , Neoplasias/terapia , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVES: Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition predominantly affecting the anogenital region in women and children. To date, there is lack of agreement amongst experts on a severity scale to aid assessment, research and treatment stratification on VLS. Furthermore, literature on best practice for long-term management of VLS is lacking. The aim of this consensus is to provide broad guidelines on the short and long-term management of VLS. METHODS: An initial focus group of Australasian experts in vulval dermatology developed a draft consensus statement for the management of VLS. Based on the results of the draft statement, a consensus panel of 22 Australasian experts, comprised of the initial and additional members, participated in an anonymous four-stage eDelphi process. Round 1 involved generation and voting on statements from the draft consensus statement developed by the focus group. In Rounds 2, 3 & 4, panel members were presented formal feedback from previous rounds and asked to indicate their level of agreement. Consensus was reached if there was ≥70% agreement on the importance of an item in the 4 (agree) to 5 (strongly agree) range. RESULTS: The expert panel, with a total of 504 collective years of experience in the field of VLS, reached consensus on a core set of 51 management statements related to diagnosis, severity, initial and long-term management, follow-up, and complications of VLS. CONCLUSIONS: This study has identified a set of management statements for VLS that may be useful in clinical practice in the Australasian population.
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Consenso , Líquen Escleroso e Atrófico/terapia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Líquen Escleroso Vulvar/terapia , Dermatologistas/normas , Feminino , Humanos , Líquen Escleroso e Atrófico/prevenção & controle , Líquen Escleroso Vulvar/prevenção & controleRESUMO
PURPOSE: Alpelisib is newly-available breast cancer agent that targets PIK3 mutations and confers a somewhat unusual adverse event profile. This study focused on older patients (≥ 65 years of age) treated outside a clinical trial to gain further experience on how these under-studied patients do with this new agent. METHODS: This descriptive, multi-site study relied on medical record review. RESULTS: Fifty-one older breast cancer patients were started on alpelisib between May 2019 and September 2020. The median age and number of comorbidities at alpelisib initiation was 71 years and 4, respectively. Thirty-five patients had stopped alpelisib (median time on drug 2.6 months (range: < 1, 9.5 months)) for the following reasons: alpelisib adverse events (n = 15), cancer progression (n = 13), and other/unknown (n = 7). Alpelisib adverse events included hyperglycemia (n = 37), diarrhea (n = 23), rash (n = 19), fatigue (n = 12), and mouth sores (n = 7); (numbers in parentheses indicate the number of patients with at least one such event). Five patients were hospitalized for hyperglycemia. At the time of report, 14 patients were deceased, and median survival had not been reached. CONCLUSION: Older patients might derive further benefit from alpelisib if the adverse event profile of this agent, particularly the hyperglycemia, were able to be better managed.
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Neoplasias da Mama , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Mutação , Tiazóis/uso terapêuticoRESUMO
PURPOSE: New technology might pose problems for older patients with cancer. This study sought to understand how a trial in older patients with cancer (Alliance A171603) was successful in capturing electronic patient-reported data. METHODS: Study personnel were invited via e-mail to participate in semistructured phone interviews, which were audio-recorded and qualitatively analyzed. RESULTS: Twenty-four study personnel from the 10 sites were interviewed; three themes emerged. The first was that successful patient-reported electronic data capture shifted work toward patients and toward study personnel at the beginning of the study. One interviewee explained, "I mean it kind of lost all advantages by being extremely laborious." Study personnel described how they ensured electronic devices were charged, wireless internet access was up and running, and login codes were available. The second theme was related to the first and dealt with data filtering. Study personnel described high involvement in data gathering; for example, one interviewee described, "I answered on the iPad, whatever they said. They didn't even want to use it at all." A third theme dealt with advantages of electronic data entry, such as prompt data availability at study completion. Surprisingly, some remarks described how electronic devices brought people together, "Some of the patients, you know, it just gave them a chance to kinda talk about, you know, what was going on." CONCLUSION: High rates of capture of patient-reported electronic data were viewed favorably but occurred in exchange for increased effort from patients and study personnel and in exchange for data that were not always patient-reported in the strictest sense.
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Neoplasias , Idoso , Eletrônica , Estudos de Viabilidade , Humanos , Neoplasias/terapia , Pesquisa QualitativaRESUMO
ABSTRACT: This analysis of notified syphilis cases in Victoria, Australia between 2015 and 2018 shows that the syphilis epidemic in Victoria has become more generalized, with increases among heterosexual men and women residing in outer Melbourne suburbs-areas that differ from those of gay men.
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Epidemias , Sífilis , Feminino , Humanos , Masculino , Sífilis/epidemiologia , Vitória/epidemiologiaRESUMO
BACKGROUND: Metastatic cancer in nonagenarians and those older is rare and understudied. Here we explored whether these patients appear to benefit from antineoplastic therapy and whether outcomes differ based on whether or not untreated patients had a histologic/cytologic confirmation of cancer. METHODS: In this single-institution, multi-site study, we reviewed 10 years of consecutive medical records of patients 90+ years of age with a histologic/cytologic cancer diagnosis and metastatic cancer or, alternatively, a presumed metastatic cancer diagnosis. RESULTS: Sixty-eight patients are the focus with a median age of 93 years (range: 90, 103 years). Patients fell into 3 groups: 1) no tissue/cytologic cancer diagnosis and no treatment (=23); 2) tissue/cytologic diagnosis but no treatment (n = 21); and 3) cancer treatment rendered (n = 24). The median survival in groups 1,2, and 3 was 5 weeks (95% confidence interval (CI): 2, 11 weeks), 9 weeks (95% CI: 3, 23 weeks), and 60 weeks (95% CI: 38 weeks, not yet reached), respectively. For those patients in group 3 who received cancer therapy, chemotherapy, radiation, and surgery were administered in 11 (16%), 6 (9%), and 4 (6%), respectively. Fourteen received other cancer therapy: hormonal therapy (n = 6), targeted therapy (n = 6), and immunotherapy (n = 2). Only one patient experienced an adverse event that required hospitalization. CONCLUSIONS: Although these older patients likely received cancer treatment on a selective basis, such treatment was associated with improved survival and was well-tolerated. However, based on survival outcomes, one might question whether to put patients through a biopsy, if they have limited therapeutic options.
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Neoplasias , Nonagenários , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias/terapiaRESUMO
BACKGROUND: The PIK3 kinase inhibitor, alpelisib, is a new breast cancer drug that can cause hyperglycemia, which can be especially severe in older patients. Yet, to our knowledge, no prior studies have sought to understand what older patients experience with alpelisib-induced hyperglycemia. METHODS: The medical records of patients who were 65 years of age or older at the initiation of alpelisib and who developed hyperglycemia were reviewed in detail; direct verbiage on hyperglycemia were extracted and reviewed with rigorous qualitative methods. RESULTS: Thirty-four women with a median age of 72 (range: 65, 85) are the subject of this report; twelve had been started on insulin, four had been hospitalized for hyperglycemia, and eleven appeared to stop alpelisib because of hyperglycemia. Qualitative analyses revealed two themes. The first was patient burden, which emanated from patients' having to self-monitor glucose levels ("Monitors blood glucose (BG) 4 times daily"); taking extra medications ("Taking Jardiance 10 mg daily and Pioglitazone 15 mg daily"); frequent changes in insulin dosing ("Her insulin was then increased ."); and frequent changes in dosing of alpelisib to help control the hyperglycemia ("Instructed to hold Piqray ."), and which also emanated from greater engagement with the healthcare system ("She was hospitalized for hyperglycemia"). The second theme focused on symptomatology and how patients suffered from hyperglycemia ("She presents to the emergency department with pre-syncope and vertigo"). CONCLUSION: Oncologists should assess older patients for the requisite abilities and resources for managing alpelisib-induced hyperglycemia in the event it occurs.
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Neoplasias da Mama , Hiperglicemia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Tiazóis/uso terapêuticoRESUMO
BACKGROUND: Nanoliposomal irinotecan (Nal-IRI) is a preferred second-line treatment for metastatic pancreas cancer. It is unclear, however, whether patients who had received irinotecan derive benefit. METHODS: Medical records of metastatic pancreas cancer patients who had received irinotecan and then Nal-IRI were reviewed. The primary endpoint was overall survival after the initiation of Nal-IRI (an a priori threshold of >4 months defined success); adverse events and quotes from the medical record on decision-making were also recorded. RESULTS: Sixty four patients met eligibility criteria with a median age of 65 years (range: 36, 80 years). The median overall survival from initiation of Nal-IRI was 5.1 months (95% confidence interval (CI): 4.3, 5.6 months). An exploratory comparison, based on no cancer progression with irinotecan versus progression, showed improved survival with Nal-IRI in the former group: 6.1 months (95% CI: 5.1, 9.3 months) versus 4.3 months (95% CI: 2.3, 4.8 months); p = 0.0006. Nal-IRI adverse events occurred as expected. Qualitative data illustrate several themes, including "limited treatment options," which appeared to drive the decision to prescribe Nal-IRI. CONCLUSION: Nal-IRI might be considered in pancreas cancer patients who had received irinotecan, particularly in the absence of disease progression with the latter.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Irinotecano/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Formas de Dosagem , Feminino , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Lipossomos , Masculino , Pessoa de Meia-Idade , NanoestruturasRESUMO
Consent forms are an important educational tool that helps cancer patients decide on whether or not to enroll on a clinical trial, but wordiness potentially detracts from their educational value. This single-institution study examined word counts of consent forms for all phase I, II, and III solid tumor clinical trials between 2004 and 2010. Consent forms were categorized by trial funding source: (1) pharmaceutical company; (2) National Clinical Trials Network (NCTN); (3) R01- or other non-government grants; and (4) mixed (funding from multiple sources). Three hundred fifteen consent forms were studied; these included 106 (34%) pharmaceutical company; 145 (46%) NCTN; 44 (14%) R01 type; and 20 (6%) mixed. The overall median word count was 5129 words per consent form (interquartile range (IQR) range, 4226 to 6695). The median word counts per consent form (IQR) were 5648 (4814, 6803), 5243 (4139, 6932), 4365 (3806, 5124), and 4319 (3862, 5944), respectively, based on the above funding sources, showing that pharmaceutical company trial consent forms had the highest median word count. Of note, phase of trial was associated with consent form length (phase III were wordier), and consent forms manifested a consistent increase in wordiness over time. These observations underscore a timely need to find ways to limit the verbosity of consent forms, particularly in those from pharmaceutical company trials.
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Ensaios Clínicos como Assunto , Termos de Consentimento , Neoplasias , Compreensão , Humanos , Consentimento Livre e Esclarecido , Neoplasias/tratamento farmacológicoRESUMO
Blooms of harmful algae are increasing globally, yet their impacts on copepods, an important link between primary producers and higher trophic levels, remain largely unknown. Algal toxins may have direct, negative effects on the survival of copepods. They may also indirectly affect copepod survival by deterring feeding and thus decreasing the availability of energy and nutritional resources. Here we present a series of short-term (24 h) experiments in which the cosmopolitan marine copepod, Acartia tonsa, was exposed to a range of concentrations of the toxic dinoflagellate, Alexandrium catenella (strain 1119/27, formerly Alexandrium tamarense), with and without the presence of alternative, non-toxic prey (Rhodomonas sp.). We also present the toxin profile concentrations for A. catenella. The survival and feeding of A. tonsa were not affected across the range of concentrations recorded for A. catenella in the field; increased mortality of A. tonsa was only discernible when A. catenella was present at concentrations that exceed their reported environmental concentrations by two orders of magnitude. The observed lethal median concentration (LC50) for A. tonsa exposed to A. catenella was 12.45 ng STX eq L-1. We demonstrate that A. tonsa is capable of simultaneously ingesting both toxic and non-toxic algae, but increases clearance rates towards non-toxic prey as the proportional abundance of toxic A. catenella increases. The ability to actively select non-toxic algae whilst also ingesting toxic algae suggests that consumption of the latter does not cause physical incapacitation and thus does not affect ingestion in A. tonsa. This work shows that short-term exposure to toxic A. catenella is unlikely to elicit major effects on the grazing or survival of A. tonsa. However, more work is needed to understand the longer-term and sub-lethal effects of toxic algae on marine copepods.
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Copépodes , Dinoflagellida , Animais , Toxinas MarinhasRESUMO
BACKGROUND: Recent studies in adults have found an incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin and piperacillin-tazobactam (TZP) that is greater than that expected with either medication alone. The purpose of this study was to determine whether combination therapy with vancomycin and TZP is associated with an incidence of AKI in pediatric patients higher than that in those on combination therapy with vancomycin and cefepime. METHODS: We performed a retrospective single-center matched-cohort study of pediatric patients who received vancomycin in combination with TZP or cefepime between January 2015 and June 2016. The patients were matched according to chronic disease, age, sex, and number of concomitant nephrotoxic medications at the time of combination antibiotic therapy. The primary outcome was incidence of AKI. Secondary outcomes included differences between groups in time to AKI, resolution of AKI, and effect of vancomycin trough levels on the incidence of nephrotoxicity. Conditional logistic regression was used to compare categorical and continuous variables between treatment groups. Conditional Poisson regression was used to assess the association between AKI and treatment groups. Stratified log-rank tests and Cox proportional hazards models with shared frailty were used to compare the times to AKI according to treatment group. RESULTS: Two hundred twenty-eight matched patients were included. AKI developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and TZP groups, respectively (P < .001). Type of combination therapy remained a significant predictor for AKI in multivariate conditional Poisson analysis in which adjustments were made for age, sex, use of concomitant nephrotoxins, and vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03). AKI developed almost 3 times sooner in the TZP group than in the cefepime group (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity analyses in which adjustment was made for antibiotic indication in addition to the aforementioned variables and excluding those with gastrointestinal infection revealed similar results. CONCLUSION: Among hospitalized children at our institution, combination therapy with vancomycin and TZP was associated with an incidence of AKI higher than that associated with vancomycin and cefepime.
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Injúria Renal Aguda/induzido quimicamente , Cefepima/toxicidade , Terapia Combinada/efeitos adversos , Combinação Piperacilina e Tazobactam/toxicidade , Vancomicina/toxicidade , Antibacterianos/efeitos adversos , Cefepima/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Combinação Piperacilina e Tazobactam/administração & dosagem , Análise de Regressão , Vancomicina/administração & dosagemRESUMO
IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.
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Interleucina-33/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/biossíntese , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologiaRESUMO
The aim of this study was to investigate if the effects of changes in physiological arousal on timing performance can be accurately predicted by the catastrophe model. Eighteen young adults (8 males, 10 females) volunteered to participate in the study following ethical approval. After familiarisation, coincidence anticipation was measured using the Bassin Anticipation Timer under four incremental exercise conditions: Increasing exercise intensity and low cognitive anxiety, increasing exercise intensity and high cognitive anxiety, decreasing exercise intensity and low cognitive anxiety and decreasing exercise intensity and high cognitive anxiety. Incremental exercise was performed on a treadmill at intensities of 30%, 50%, 70% and 90% heart rate reserve (HRR) respectively. Ratings of cognitive anxiety were taken at each intensity using the Mental Readiness Form 3 (MRF3) followed by performance of coincidence anticipation trials at speeds of 3 and 8 mph. Results indicated significant condition × intensity interactions for absolute error (AE; p = .0001) and MRF cognitive anxiety intensity scores (p = .05). Post hoc analysis indicated that there were no statistically significant differences in AE across exercise intensities in low-cognitive anxiety conditions. In high-cognitive anxiety conditions, timing performance AE was significantly poorer and cognitive anxiety higher at 90% HRR, compared to the other exercise intensities. There was no difference in timing responses at 90% HRR during competitive trials, irrespective of whether exercise intensity was increasing or decreasing. This study suggests that anticipation timing performance is negatively affected when physiological arousal and cognitive anxiety are high.