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1.
bioRxiv ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38952794

RESUMO

The microbiota can promote host health by inhibiting pathogen colonization, yet how host-resident fungi, or the mycobiota, contribute to this process remains unclear. The human skin mycobiota is uniquely stable compared to other body sites and dominated by yeasts of the genus Malassezia . We observe that colonization of human skin by Malassezia sympodialis significantly reduces subsequent colonization by the prominent bacterial pathogen Staphylococcus aureus . M. sympodialis secreted products possess potent bactericidal activity against S. aureus and are sufficient to impair S. aureus skin colonization. This bactericidal activity requires an acidic environment and is exacerbated by free fatty acids, demonstrating a unique synergy with host-derived epidermal defenses. Leveraging experimental evolution to pinpoint mechanisms of S. aureus adaptation in response to the skin mycobiota, we identified multiple mutations in the stringent response regulator Rel that promote survival against M. sympodialis . Similar Rel alleles have been reported in S. aureus clinical isolates, and natural Rel variants are sufficient for tolerance to M. sympodialis antagonism. Partial stringent response activation underlies tolerance to clinical antibiotics, with both laboratory-evolved and natural Rel variants conferring multidrug tolerance. These findings demonstrate the ability of the mycobiota to mediate pathogen colonization resistance, identify new mechanisms of bacterial adaptation in response to fungal antagonism, and reveal the potential for microbiota-driven evolution to shape pathogen antibiotic susceptibility. Highlights: - M. sympodialis reduces colonization of human skin by S. aureus - Bactericidal activity of M. sympodialis is exacerbated by features of the skin niche - S. aureus Rel variants are sufficient for tolerance to Malassezia antagonism - Evolved tolerance to yeast antagonism coincides with S. aureus multidrug tolerance.

2.
Pharmacoepidemiol Drug Saf ; 33(7): e5853, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973415

RESUMO

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs). METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs. RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33. CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacêuticos , Papel Profissional , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Farmacêuticos/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Ecology ; 105(7): e4328, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782017

RESUMO

Since 1968, the Australian Dung Beetle Project has carried out field releases of 43 deliberately introduced dung beetle species for the biological control of livestock dung and dung-breeding pests. Of these, 23 species are known to have become established. For most of these species, sufficient time has elapsed for population expansion to fill the extent of their potential geographic range through both natural and human-assisted dispersal. Consequently, over the last 20 years, extensive efforts have been made to quantify the current distribution of these introduced dung beetles, as well as the seasonal and spatial variation in their activity levels. Much of these data and their associated metadata have remained unpublished, and they have not previously been synthesized into a cohesive dataset. Here, we collate and report data from the three largest dung beetle monitoring projects from 2001 to 2022. Together, these projects encompass data collected from across Australia, and include records for all 23 species of established dung beetles introduced for biocontrol purposes. In total, these data include 22,718 presence records and 213,538 absence records collected during 10,272 sampling events at 546 locations. Most presence records (97%) include abundance data. In total, 1,752,807 dung beetles were identified as part of these data. The distributional occurrence and abundance data can be used to explore questions such as factors influencing dung beetle species distributions, dung beetle biocontrol, and insect-mediated ecosystem services. These data are provided under a CC-BY-NC 4.0 license and users are encouraged to cite this data paper when using the data.


Assuntos
Besouros , Espécies Introduzidas , Besouros/fisiologia , Animais , Austrália , Fatores de Tempo , Distribuição Animal , Dinâmica Populacional , Densidade Demográfica
4.
Artigo em Inglês | MEDLINE | ID: mdl-38633403

RESUMO

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

5.
Proc Natl Acad Sci U S A ; 121(13): e2320410121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38498718

RESUMO

Biofilms of sulfate-reducing bacterium (SRB) like Desulfovibrio vulgaris Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses. Although the mechanisms of biofilm formation by DvH are not yet well understood, recent studies indicate the large adhesin, DvhA, is a key determinant of biofilm formation. The dvhA gene neighborhood resembles the biofilm-regulating Lap system of Pseudomonas fluorescens but is curiously missing the c-di-GMP-binding regulator LapD. Instead, DvH encodes an evolutionarily unrelated c-di-GMP-binding protein (DVU1020) that we hypothesized is functionally analogous to LapD. To study this unusual Lap system and overcome experimental limitations with the slow-growing anaerobe DvH, we reconstituted its predicted SRB Lap system in a P. fluorescens strain lacking its native Lap regulatory components (ΔlapGΔlapD). Our data support the model that DvhA is a cell surface-associated LapA-like adhesin with a N-terminal "retention module" and that DvhA is released from the cell surface upon cleavage by the LapG-like protease DvhG. Further, we demonstrate DVU1020 (named here DvhD) represents a distinct class of c-di-GMP-binding, biofilm-regulating proteins that regulates DvhG activity in response to intracellular levels of this second messenger. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.


Assuntos
Pseudomonas fluorescens , Pseudomonas fluorescens/genética , Pseudomonas fluorescens/metabolismo , Sulfatos/metabolismo , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Biofilmes , Proteínas de Transporte/metabolismo , GMP Cíclico/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica
6.
J Cardiothorac Surg ; 19(1): 44, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310294

RESUMO

Transesophageal echocardiography (TEE) has become an indispensable part of cardiothoracic surgery at present and is considered to be a safe procedure, rarely associated with complications. However, TEE may cause serious and life threatening complications, as presented in this case report. We describe a patient who developed an empyema after elective cardiac surgery due to an esophageal perforation caused by TEE, without any clinical symptoms. Risk factors for TEE-related complications, identified in recent literature, will be discussed as well as the remarkable absence of clinical symptoms in this particular patient.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Perfuração Esofágica , Humanos , Perfuração Esofágica/diagnóstico por imagem , Perfuração Esofágica/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia Transesofagiana , Fatores de Risco , Procedimentos Cirúrgicos Eletivos/efeitos adversos
8.
bioRxiv ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38045380

RESUMO

Biofilms of the sulfate reducing bacterium (SRB) Desulfovibrio vulgaris Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses; however, the mechanisms of biofilm formation by DvH are not yet well-understood. Evidence suggests that a large adhesin, DvhA, may be contributing to biofilm formation in DvH. The dvhA gene and its neighbors encode proteins that resemble the Lap system, which regulates biofilm formation by Pseudomonas fluorescens, including a LapG-like protease DvhG and effector protein DvhD, which has key differences from the previously described LapD. By expressing the Lap-like adhesion components of DvH in P. fluorescens, our data support the model that the N-terminal fragment of the large adhesin DvhA serves as an adhesin "retention module" and is the target of the DvhG/DvhD regulatory module, thereby controlling cell-surface location of the adhesin. By heterologously expressing the DvhG/DvhD-like proteins in a P. fluorescens background lacking native regulation (ΔlapGΔlapD) we also show that cell surface regulation of the adhesin is dependent upon the intracellular levels of c-di-GMP. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.

9.
Rhinology ; 61(6): 519-530, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37804121

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.


Assuntos
Obstrução Nasal , Pólipos Nasais , Rinite , Sinusite , Humanos , Consenso , Qualidade de Vida , Técnica Delphi , Rinite/diagnóstico , Sinusite/diagnóstico , Sinusite/terapia , Corticosteroides , Doença Crônica , Pólipos Nasais/diagnóstico
10.
Anaesthesia ; 78(12): 1472-1480, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37877784

RESUMO

The current pandemic of surgical complications necessitates urgent and pragmatic innovation to reduce postoperative morbidity and mortality, which are associated with poor pre-operative fitness and anaemia. Exercise prehabilitation is a compelling strategy, but it has proven difficult to establish that it improves outcomes either in isolation or as part of a multimodal approach. Simulated altitude exposure improves performance in athletes and offers a novel potential means of improving cardiorespiratory and metabolic fitness and alleviating anaemia within the prehabilitation window. We aimed to provide an initial physiological foundation for 'altitude prehabilitation' by determining the physiological effects of one week of simulated altitude (FI O2 15%, equivalent to approximately 2438 m (8000 ft)) in older sedentary volunteers. The study used a randomised, double-blind, sham-controlled crossover design. Eight participants spent counterbalanced normoxic and hypoxic weeks in a residential hypoxia facility and underwent repeated cardiopulmonary exercise tests. Mean (SD) age of participants was 64 (7) y and they were unfit, with mean (SD) baseline anaerobic threshold 12 (2) ml.kg-1 .min-1 and mean (SD) peak V̇O2 15 (3) ml.kg-1 .min-1 . Hypoxia was mild (mean (SD) Sp O2 93 (2) %, p < 0.001) and well-tolerated. Despite some indication of greater peak exercise capacity following hypoxia, overall there was no effect of simulated altitude on anaerobic threshold or peak V̇O2 . However, hypoxia induced a substantial increase in mean (SD) haemoglobin of 1.5 (2.7) g.dl-1 (13% increase, p = 0.028). This study has established the concept and feasibility of 'altitude prehabilitation' and demonstrated specific potential for improving haematological fitness. Physiologically, there is value in exploring a possible role for simulated altitude in pre-operative optimisation.


Assuntos
Anemia , Exercício Pré-Operatório , Humanos , Idoso , Altitude , Consumo de Oxigênio/fisiologia , Hipóxia
11.
J Helminthol ; 97: e63, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37522182

RESUMO

Given the threat presented by parasites and pathogens, insects employ various defences to protect themselves against infection, including chemical secretions. The red flour beetle Tribolium castaneum releases a secretion containing the benzoquinones methyl-1,4-benzoquinone (MBQ) and ethyl-1,4-benzoquinone (EBQ) into the environment. These compounds have known antimicrobial effects; however, their role in defence against macroparasites is not known. Entomopathogenic nematodes, such as Steinernema carpocapsae, present a serious threat to insects, with successful infection leading to death. Thus, quinone-containing secretions may also aid in host defence. We tested how exposure to the individual components of this quinone secretion, as well as a mix at naturally-occurring proportions, affected the survival and thrashing behaviour of S. carpocapsae, as well as their virulence to a model host (Galleria mellonella). Exposure to high concentrations of MBQ and EBQ, as well as the quinone mix, significantly increased nematode death but did not consistently reduce thrashing, which would otherwise be expected given their toxicity. Rather, quinones may act as a host cue to S. carpocapsae by triggering increased activity. We found that exposure to quinones for 24 or 72 hours did not reduce nematode virulence, and surviving nematodes remained infective after non-lethal exposure. Our results indicate that quinone secretions likely serve as a defence against multiple infection threats by reducing S. carpocapsae survival, but further research is required to contextualize their roles by testing against other nematodes, as well as other helminths using insects as hosts.

12.
Cell Host Microbe ; 31(8): 1371-1385.e6, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37516109

RESUMO

In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but it also provides glycan cues that regulate microbial behaviors. Here, we describe a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates the expression of an aggregation-promoting adhesin we named MbpA. Upon MbpA disruption, Aer01 colonizes to normal levels but is largely planktonic and more pro-inflammatory. Increasing cell surface MbpA rescues these traits. MbpA-like adhesins are common in human-associated bacteria, and the expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restores lumenal aggregation and reverses its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.


Assuntos
Mucinas , Peixe-Zebra , Animais , Humanos , Mucinas/metabolismo , Bactérias/metabolismo , Polissacarídeos/metabolismo , Epitélio/metabolismo
13.
Ageing Res Rev ; 88: 101953, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182743

RESUMO

The impact of oral nutritional supplements (ONS) on patients with complications (disease related morbidity) requires further exploration. This systematic review included 44 randomised controlled trials (RCT) (29 RCT surgical, 15 RCT medical patients) examining the effect of ONS in community settings on the incidence of complications (n = 716, mean age 67 years, range 35-87). ONS (mean intake 588 kcal/day, range 125-1750; protein 22 g/day, range 0-54; mean energy from protein 22 %, range 0-54) were prescribed for a mean 74 days, range 5-365. Most RCT (77 %) reported fewer complications in the ONS group versus control. Meta-analysis (39 RCT) showed ONS consumption reduced complications including infections, pressure ulcers, wound and fracture healing (OR 0.68, 95 % CI 0.59,0.79; p<0.001). Results showed reductions when ONS were used in hospital and community settings (OR 0.72, 95 % CI 0.59,0.87; p = 0.001) or just in the community (OR 0.65, 95 % CI 0.52, 0.80; p<0.001). Reductions in complications were only seen with high ONS adherence ≥ 80 % (OR 0.63, 95 % CI 0.48,0.83; p = 0.001) and ready-to-drink ONS (OR 0.69, 95 % CI 0.60,0.81; p<0.001). This systematic review and meta-analysis show community-based use of ONS in addition to the diet substantially reduces the incidence of complications. The diversity of ONS, patient populations and complication outcomes within the trials included in this review mean further research is warranted.


Assuntos
Suplementos Nutricionais , Desnutrição , Humanos , Idoso , Idoso de 80 Anos ou mais
14.
Gut Microbes ; 15(1): 2183686, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36859771

RESUMO

In response to microbiota colonization, the intestinal epithelia of many animals exhibit increased rates of cell proliferation. We used gnotobiotic larval zebrafish to identify a secreted factor from the mutualist Aeromonas veronii that is sufficient to promote intestinal epithelial cell proliferation. This secreted A. veronii protein is a homologue of the Vibrio cholerae GlcNAc binding protein GbpA, which was identified as a chitin-binding colonization factor in mice. GbpA was subsequently shown to be a lytic polysaccharide monooxygenase (LPMO) that can degrade recalcitrant chitin. Our phenotypic characterization of gbpA deficient A. veronii found no alterations in these cells' biogeography in the zebrafish intestine and only a modest competitive disadvantage in chitin-binding and colonization fitness when competed against the wild-type strain. These results argue against the model of GbpA being a secreted adhesin that binds simultaneously to bacterial cells and GlcNAc, and instead suggests that GbpA is part of a bacterial GlcNAc utilization program. We show that the host proliferative response to GbpA occurs in the absence of bacteria upon exposure of germ-free zebrafish to preparations of native GbpA secreted from either A. veronii or V. cholerae or recombinant A. veronii GbpA. Furthermore, domain 1 of A. veronii GbpA, containing the predicted LPMO activity, is sufficient to stimulate intestinal epithelial proliferation. We propose that intestinal epithelial tissues upregulate their rates of renewal in response to secreted bacterial GbpA proteins as an adaptive strategy for coexisting with bacteria that can degrade glycan constituents of the protective intestinal lining.


Assuntos
Aeromonas , Microbioma Gastrointestinal , Animais , Camundongos , Proteínas de Transporte , Peixe-Zebra , Intestinos , Proliferação de Células , Proteínas de Bactérias , Quitina
15.
J Hosp Infect ; 134: 138-146, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36801429

RESUMO

BACKGROUND: Uropathogenic Escherichia coli (UPEC) are a primary cause of catheter-associated urinary tract infections (CAUTIs), often forming mature recalcitrant biofilms on the catheter surface. Anti-infective catheter coatings containing single biocides have been developed but display limited antimicrobial activity due to the selection of biocide-resistant bacterial populations. Furthermore, biocides often display cytotoxicity at concentrations required to eradicate biofilms, limiting their antiseptic potential. Quorum-sensing inhibitors (QSIs) provide a novel anti-infective approach to disrupt biofilm formation on the catheter surface and help prevent CAUTIs. AIM: To evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bactericidal and biofilm eradication concentrations in parallel to assessing cytotoxicity in a bladder smooth muscle (BSM) cell line. METHODS: Checkerboard assays were performed to determine fractional inhibitory, bactericidal, and biofilm eradication concentrations of test combinations in UPEC and combined cytotoxic effects in BSM cells. FINDINGS: Synergistic antimicrobial activity was observed between polyhexamethylene biguanide, benzalkonium chloride or silver nitrate in combination with either cinnamaldehyde or furanone-C30 against UPEC biofilms. However, furanone-C30 was cytotoxic at concentrations below those required even for bacteriostatic activity. A dose-dependent cytotoxicity profile was observed for cinnamaldehyde when in combination with BAC, PHMB or silver nitrate. Both PHMB and silver nitrate displayed combined bacteriostatic and bactericidal activity below the half-maximum inhibitory concentration (IC50). Triclosan in combination with both QSIs displayed antagonistic activity in both UPEC and BSM cells. CONCLUSION: PHMB and silver in combination with cinnamaldehyde display synergistic antimicrobial activity in UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.


Assuntos
Anti-Infecciosos , Desinfetantes , Infecções por Escherichia coli , Infecções Urinárias , Humanos , Desinfetantes/farmacologia , Nitrato de Prata/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Biofilmes , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia
17.
Value Health ; 26(3): 384-391, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36706950

RESUMO

OBJECTIVES: The zero-price conundrum occurs when a clinically effective drug can justify no greater than a price of zero based on cost-effectiveness criteria from a health system perspective. This is relevant for health systems that require evidence of cost-effectiveness, in addition to safety and efficacy for drug approval and other analyses that may shape drug coverage policies, such as budget impact and comparative effectiveness. This study aimed to clarify and explore the zero-price conundrum to provide a resource in the development of practical and methodological solutions. METHODS: We specified equations representing previously identified zero-price scenarios and used them to elucidate factors contributing to the zero-price conundrum and explore relationships between them. We present real-world considerations and discuss solutions from the literature. RESULTS: The analyses demonstrated that a primary cause of the zero-price problem for a new drug that increases quality-adjusted survival pertains to healthcare costs beyond the influence of the new drug, specifically, disease background costs, costs of existing drugs used in a combination regimen, and costs of future health interventions patients may become eligible to receive. Pragmatic solutions have been to exclude such costs from cost-effectiveness analyses. Proposed modifications to cost-effectiveness analysis include assessing each drug in a combination regimen based on its relative contribution to improved health. CONCLUSIONS: The zero-price dilemma may arise more frequently as the number of drugs in high-cost disease areas continues to grow. As cost-effectiveness methods evolve, there is the opportunity to develop robust solutions that can be applied consistently.


Assuntos
Análise de Custo-Efetividade , Custos de Cuidados de Saúde , Humanos , Análise Custo-Benefício
18.
J Clin Oncol ; 41(3): 425-435, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36649675

RESUMO

PURPOSE: Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. METHODS: A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. RESULTS: A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. CONCLUSION: IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.

19.
Tech Coloproctol ; 27(4): 291-296, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36175722

RESUMO

BACKGROUND: The aim of this study was to assess the effect of preoperative biologic therapy on the surgical outcome of Crohn's disease (CD) patients undergoing repeat ileocolic resection. METHODS: This was a retrospective analysis of all CD patients who underwent repeat ileocolic resection at Cleveland Clinic Florida between January 2011 and April 2021. Patients were divided into two groups: treatment biologic therapy prior to surgery and controls. RESULTS: Sixty-five patients (31males, median age 54 [range 23-82] years) were included in the study. Twenty nine (44.6%) were treated with biologic therapy prior to repeat ileocolic resection. No demographic differences were found between the biologic therapy and control groups. In addition, no differences were found in mean time from index ileocolic resection (p = 0.9), indication for surgery (p = 0.11), and preoperative albumin (p = 0.69). The majority of patients (57; 87.7%) were operated on laparoscopically, and mean overall operation time was 225 (SD 49.27) min. Overall, the postoperative complication rate was 43.1% (28 patients) and median length of stay was 5 (range 2-21) days. Postoperative complications were more common in the control group, compared to the biologic therapy group (55.6 vs 27.5%; p = 0.04). Conversion rate (35.7 vs 20.7%; p = 0.24), operation time (223 vs 219 min; p = 0.75), length of stay (5.2 vs 5.9 days; p = 0.4), and readmission (16.6 vs 11.1%; p = 0.72) were similar between the two groups. Multivariate analysis of risk factors for postoperative complications showed that biologic treatment was correlated with a lower risk (HR -0.28, CI 95% -0.5596 to -0.01898, p = 0.03). CONCLUSIONS: Patients treated with biologic therapy for CD who underwent repeat ileocolic resection had fewer postoperative complications.


Assuntos
Doença de Crohn , Laparoscopia , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Crohn/cirurgia , Estudos Retrospectivos , Intestinos/cirurgia , Complicações Pós-Operatórias/cirurgia , Terapia Biológica , Íleo/cirurgia , Resultado do Tratamento
20.
Nat Commun ; 13(1): 4651, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085141

RESUMO

X-ray imaging has been boosted by the introduction of phase-based methods. Detail visibility is enhanced in phase contrast images, and dark-field images are sensitive to inhomogeneities on a length scale below the system's spatial resolution. Here we show that dark-field creates a texture which is characteristic of the imaged material, and that its combination with conventional attenuation leads to an improved discrimination of threat materials. We show that remaining ambiguities can be resolved by exploiting the different energy dependence of the dark-field and attenuation signals. Furthermore, we demonstrate that the dark-field texture is well-suited for identification through machine learning approaches through two proof-of-concept studies. In both cases, application of the same approaches to datasets from which the dark-field images were removed led to a clear degradation in performance. While the small scale of these studies means further research is required, results indicate potential for a combined use of dark-field and deep neural networks in security applications and beyond.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Microscopia de Contraste de Fase , Radiografia , Raios X
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