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The recent biological invasion of box tree moth Cydalima perspectalis on Buxus trees has a major impact on European boxwood stands through severe defoliation. This can hinder further regrowth and threaten survival of populations. In a mesocosm approach and controlled larval density over a 2-month period, responses of B. sempervirens essential and specialized metabolites were characterized using metabolomics, combining 1H-NMR and LC-MS/MS approaches. This is the first metabolome depiction of major Buxus responses to boxwood moth invasion. Under severe predation, remaining green leaves accumulate free amino acids (with the noticeable exception of proline). The leaf trans-4-hydroxystachydrine and stachydrine reached 10-13% and 2-3% (DW), while root content was lower but also modulated by predation level. Larval predation promoted triterpenoid and (steroidal) alkaloid synthesis and diversification, while flavonoids did not seem to have a relevant role in Buxus resistance. Our results reveal the concomitant responses of central and specialized metabolism, in relation to severity of predation. They also confirm the potential of metabolic profiling using 1H-NMR and LC-MS to detect re-orchestration of metabolism of native boxwood after severe herbivorous predation by the invasive box-tree moth, and thus their relevance for plant-insect relationships and ecometabolomics.
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Poly L(+) lactic acid (PLLA) has become crucial in the biomedical industry for various uses. The direct polycondensation method was used to prepare Poly L(+) Lactic Acid (PLLA). Different catalysts, including metal oxides and metal halides, were used to test the polymerization technique. The effect of the amount of catalysts and the type of coupling agent were investigated. The effect of reaction time and polymerization solvents was also studied. PLLA was loaded with isosorbide dinitrate utilizing the solvent evaporation process. The synthesized polymer-drug system was evaluated by different means such as FT-IR, TGA, DSC, XRD, entrapment efficiency (E.E), drug loading (D.L), particle size analysis, and zeta potential determination. Studies on in-vitro release using UV light at 227 nm at various pH levels were conducted, and the kinetics of release and cytotoxicity using the sulforhodamine B (SRB) assay on human skin fibroblast cells were examined.
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PURPOSE: Traumatic crush injuries of the lower limb often accompany severe complications. The incorporation of hyperbaric oxygen therapy to standard trauma care may have the potential to diminish injury-related complications and improve outcome in such cases. This systematic review aims to evaluate the effectiveness of hyperbaric oxygen therapy in the management of severe lower limb soft tissue injuries. METHODS: The electronic databases Medline, Embase and Cochrane Library were searched to identify studies involving patients with crush-associated sever lower limb soft tissue injuries who received hyperbaric oxygen therapy in conjunction with standard trauma care. Relevant data on type of injury, hyperbaric oxygen therapy protocol and outcome related to wound healing were extracted. RESULTS: In total seven studies met the inclusion criteria, involving 229 patients. The studies included two randomized clinical trials, one retrospective cohort study, three case series and one case report. The randomized placebo-controlled clinical trial showed a significant increase in wound healing and decrease in the need for additional surgical interventions in the patient group receiving hyperbaric oxygen therapy when compared to those undergoing sham therapy. The randomized non-placebo-controlled clinical trial revealed that early hyperbaric oxygen therapy reduces tissue necrosis and the likelihood of long-term complications. The retrospective cohort study indicated that hyperbaric oxygen therapy effectively reduces infection rates and the need for additional surgical interventions. The case series and case report presented beneficial results with regard to wound healing when hyperbaric oxygen therapy was added to the treatment regimen. CONCLUSION: Hyperbaric oxygen therapy is generally considered a safe therapeutic intervention and seems to have a beneficial effect on wound healing in severe lower limb soft tissue injuries when implemented as an addition to standard trauma care.
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Oxigenoterapia Hiperbárica , Lesões dos Tecidos Moles , Cicatrização , Oxigenoterapia Hiperbárica/métodos , Humanos , Lesões dos Tecidos Moles/terapia , Lesões por Esmagamento/terapia , Traumatismos da Perna/terapia , Extremidade Inferior/lesõesRESUMO
BACKGROUND: The updated 2014 BTA guidelines emphasised a more conservative, risk adapted model for the management of low-risk differentiated thyroid cancer (DTC). In comparison to historical approach of total thyroidectomy combined with radioactive iodine, treatment de-escalation is increasingly supported. AIMS: To evaluate the impact of the updated BTA guidelines on the management of DTC cases at regional UK centre. METHODS: All DTC patients were retrospectively identified from regional thyroid MDT database between Jan2009-Dec2020. Oncological treatment and clinico-pathological characteristics were analysed. RESULTS: 623 DTC cases were identified; 312 (247 female: 65 male) between 2009 and 2014 and 311 (225 female: 86 male) between 2015 and 2020. Median age is 48 years (range 16-85). By comparing pre- and post-2015 cohorts, there was a significant drop in total thyroidectomy (87.1% vs 76.8%, p = 0.001) and the use of radioactive iodine (RAI) (73.1% vs 62.1%, p = 0.003) in our post-2015 cohort. When histological adverse features were analysed, extra-thyroidal extension (4.2% vs 17.0%, p=< 0.001), lymphovascular invasion (31.4% vs 50.5%, p=<0.001) and multi-centricity (26.9% vs 43.4%, p = 0.001) were significantly increased in the post 2015 cohort. Nonetheless, total thyroidectomy (TT) remains the treatment choice for low risk T1/2 N0 M0 disease in 65.3% (124/190) in post-2015 cohort for several reasons. Reasons include adverse histological features (50.8%), benign indications (32.5%), contralateral nodules (11.7%), patient preference (2.5%), and diagnostic uncertainty (2.5%). CONCLUSION: Our study confirms a move towards a more conservative approach to patients with low-risk DTC in the UK, which is in keeping with the BTA 2014 guideline and international trends, but total thyroidectomy remains prevalent for low risk T1/2 N0 M0 disease for other reasons.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Estudos Retrospectivos , Radioisótopos do Iodo , TireoidectomiaRESUMO
AIM: Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment. METHODS: 577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated. RESULTS: Of 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106-4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification. CONCLUSION: Although multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/patologia , Metástase Linfática , Estudos Retrospectivos , Prognóstico , Tireoidectomia , Fatores de Risco , Recidiva Local de Neoplasia/patologiaRESUMO
This study investigates patients' access to surgical care for burns in a low- and middle-income setting by studying timeliness, surgical capacity, and affordability. A survey was conducted in a regional referral hospital in Manyara, Tanzania. In total, 67 patients were included. To obtain information on burn victims in need of surgical care, irrespective of time lapsed from the burn injury, both patients with burn wounds and patients with contractures were included. Information provided by patients and/or caregivers was supplemented with data from patient files and interviews with hospital administration and physicians. In the burn wound group, 50% reached a facility within 24 hours after the injury. Referrals from other health facilities to the regional referral hospital were made within 3 weeks for 74% in this group. Of contracture patients, 74% had sought healthcare after the acute burn injury. Of the same group, only 4% had been treated with skin grafts beforehand, and 70% never received surgical care or a referral. Together, both groups indicated that lack of trust, surgical capacity, and referral timeliness were important factors negatively affecting patient access to surgical care. Accounting for hospital fees indicated patients routinely exceeded the catastrophic expenditure threshold. It was determined that healthcare for burn victims is without financial risk protection. We recommend strengthening burn care and reconstructive surgical programs in similar settings, using a more comprehensive health systems approach to identify and address both medical and socioeconomic factors that determine patient mortality and disability.
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Queimaduras , Contratura , Queimaduras/cirurgia , Contratura/cirurgia , Custos e Análise de Custo , Países em Desenvolvimento , Hospitais , Humanos , Encaminhamento e Consulta , TanzâniaRESUMO
INTRODUCTION: Very little data are available regarding differentiated thyroid cancer (DTC) managed in the UK, and no UK patients are included in the evidence base upon which international guidelines are based. Therefore, the aim of this study was to compare the clinicopathological features of patients with DTC presenting in a UK population with international patient cohorts. PATIENTS AND METHODS: Data were collected from a prospectively held multi-disciplinary team records from January 2009 to December 2016. The local cohort was compared with cohorts from across the world based on clinicopathological features. Ethical approval was obtained by Lothian Caldicott Guardian (Ref 16 133). RESULTS: 444 cases were diagnosed locally with a median age of 48 years (range 16-86 years). 78% of patients were female. 25% of our patients had follicular carcinoma with an overall N1 rate of 20%. Distant disease was recorded in 5% cases. In comparison with international data, our local cohort had a higher rate of follicular thyroid carcinoma. Variation was seen in terms of age, gender distribution, primary tumour size, nodal and distant disease. In Korea, where thyroid cancer screening has been undertaken, smaller tumours, higher rates of nodal disease and lower rates of distant disease are described. CONCLUSION: In our centre, a higher rate of males is treated with larger primary disease and a higher percentage of follicular carcinoma. The reasons for this geographic variation in clinicopathological features in the UK are unclear. As a result, caution should be applied in translating the international move towards a more conservative approach to DTC in the UK in comparison with other areas of the world.
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Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Glândula Tireoide/terapia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Differentiated thyroid cancer (DTC) is increasing in incidence but little is known about oncological outcomes for patients treated in the UK. Internationally there is a move toward conservative treatment of DTC. However, this is based on evidence from outside the UK. The aim of this study was to analyse oncological outcomes for a contemporary cohort of patients treated in a UK centre. METHODS: Review of 470 consecutive prospectively recorded cases of DTC from the South East of Scotland endocrine MDT 2009-2018. Data on patient, tumour and treatment details as well as recurrence and survival details were extracted from the electronic patient record. RESULTS: Of 470 patients female:male ratio was 3.4:1, median age at presentation was 48 years (range 16-86 years). Overall 193 (41%), 134 (29%), 119 (25%) and 22 (5%) patients were p T1, T2, T3, and p T4 respectively. 385 patients (82%) were pN0, 31 patients (7%) were pN1a and 53 patients (11%) were pN1b. 19 patients (4%) were M1. Of 470 patients 350 (74%) had papillary thyroid carcinoma, 120 patients (26%) had follicular carcinoma. Surgical management was lobectomy, isthumusectomy, total thyroidectomy and lobectomy then completion thyroidectomy in 14%,1%, 41% and 43% cases respectively. 64% patients received radioactive Iodine (RAI) therapy. With a median follow-up of 70 months (range 4-124 months), 5 years overall survival and disease specific survival were 96.7% and 98.5% respectively. The 5 year local recurrence free survival (LRFS), regional recurrence free survival (RRFS), locoregional recurrence free survival (LRRFS), distant recurrence free survival (DRFS) and any recurrence free survivals were 100%, 95.8%, 95.8%, 98.3% and 95% respectively. CONCLUSION: Oncological outcomes for patients treated with DTC were excellent, in keeping with experience from international groups, suggesting that a move towards conservative treatment in the UK seems reasonable.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Escócia/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do Tratamento , Adulto JovemRESUMO
Background and purpose - Congenital pseudarthrosis of the tibia (CPT) is caused by local periosteal disease that can lead to bowing, fracturing, and pseudarthrosis. Current most successful treatment methods are segmental bone transport and vascularized and non-vascularized bone grafting. These methods are commonly hampered by discomfort, reoperations, and long-term complications. We report a combination of a vascularized fibula graft and large bone segment allograft, to improve patient comfort with similar outcomes.Patients and methods - 7 limbs that were operated on in 6 patients between November 2007 and July 2018 with resection of the CPT and reconstruction with a vascularized fibula graft in combination with a bone allograft were retrospectively studied. The mean follow-up time was 5.4 years (0.9-9.6). Postoperative endpoints: time to discharge, time to unrestricted weight bearing, complications within 30 days, consolidation, number of fractures, and secondary deformities.Results - The average time to unrestricted weight bearing with removable orthosis was 3.5 months (1.2-7.8). All proximal anastomoses consolidated within 10 months (2-10). 4 of the 7 grafts fractured at the distal anastomosis between 6 and 14 months postoperatively. After reoperation, consolidation of the distal anastomosis was seen after 2.8 months (2-4). 1 patient required a below-knee amputation.Interpretation - This case series showed favorable results of the treatment of CPT through a combination of a vascularized fibula graft and large bone segment allograft, avoiding the higher reintervention rate and discomfort with ring frame bone transport, and the prolonged non-weight bearing with vascularized fibula transfer without reinforcement with a massive large bone segment allograft.
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Transplante Ósseo/métodos , Fíbula/irrigação sanguínea , Fíbula/transplante , Pseudoartrose/congênito , Tíbia/cirurgia , Adolescente , Aloenxertos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pseudoartrose/cirurgia , Estudos RetrospectivosRESUMO
We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14-17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and longitudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource.
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Transtornos de Ansiedade/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Encéfalo/fisiopatologia , Depressão/diagnóstico por imagem , Neuroimagem , Adolescente , Transtornos de Ansiedade/fisiopatologia , Boston , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Conectoma/métodos , Depressão/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodosRESUMO
BACKGROUND: Total laryngectomy is often utilised to manage squamous cell carcinoma of the larynx or hypopharynx. This study reports on surgical trends and outcomes over a 10-year period. METHOD: A retrospective review of patients undergoing total laryngectomy for squamous cell carcinoma was performed (n = 173), dividing patients into primary and salvage total laryngectomy cohorts. RESULTS: A shift towards organ-sparing management was observed. Primary total laryngectomy was performed for locoregionally advanced disease and utilised reconstruction less than salvage total laryngectomy. Overall, 11 per cent of patients developed pharyngocutaneous fistulae (primary: 6 per cent; salvage: 20 per cent) and 11 per cent neopharyngeal stenosis (primary: 9 per cent; salvage: 15 per cent). Pharyngocutaneous fistulae rates were higher in the reconstructed primary total laryngectomy group (24 per cent; 4 of 17), compared with primary closure (3 per cent; 3 of 90) (p = 0.02). Patients were significantly more likely to develop neopharyngeal stenosis following pharyngocutaneous fistulae in salvage total laryngectomy (p = 0.01) and reconstruction in primary total laryngectomy (p = 0.02). Pre-operative haemoglobin level and adjuvant treatment failed to predict pharyngocutaneous fistulae development. CONCLUSION: Complications remain hard to predict and there are continuing causes of morbidity. Additionally, prior treatment continues to affect surgical outcomes.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Causalidade , Fístula Cutânea/epidemiologia , Fístula Cutânea/etiologia , Feminino , Humanos , Laringoestenose/epidemiologia , Laringoestenose/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/epidemiologia , Doenças Faríngeas/etiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: Microbial point-of-care testing (POCT) has potential to revolutionize clinical care. Understanding the prognostic value of microbes identified from the upper respiratory tract (a convenient sampling site) is a necessary first step to understand potential for upper respiratory tract POCTs in assisting antimicrobial treatment decisions for respiratory infections (RTIs). The aim was to investigate the relationship between upper respiratory tract microbial detection and disease prognosis, including effects of antimicrobial use. METHODS: Data sources were the MEDLINE and Embase databases. Study eligibility criteria consisted of quantitative studies reporting microbiological and prognostic data from patients of all age groups presenting with RTI. Patients presenting to healthcare or research settings with RTI participated. Interventions included upper respiratory tract swab. The methods used were systematic review and meta-analysis. RESULTS: Searches identified 5156 articles, of which 754 were duplicates and 4258 excluded on title or abstract. A total of 144 full texts were screened; 21 articles were retained. Studies reported data for 15 microbes and 26 prognostic measures (390 potential associations). One hundred and seven (27%) associations were investigated statistically, of which 38 (36%) were significant. Most studies reported only prognostic value of test positive results. Meta-analyses suggested hospitalization duration was longer for patients with respiratory syncytial virus than adenovirus and influenza, but significant heterogeneity was observed between studies. CONCLUSIONS: A quarter of potential prognostic associations have been investigated. Of these, a third were significant, suggesting considerable potential for POCT. Future research should investigate prognostic value of positive and negative tests, and interactions between test results, use of antimicrobials and microbial resistance.
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Testes Diagnósticos de Rotina/métodos , Testes Imediatos , Infecções Respiratórias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: The aetiology of capsular contracture around breast implants remains unclear. The leading theory is that a subclinical infection around the implant plays a role in the development of capsular contractions. Several studies found associations between the presence of bacteria and the occurrence of capsular contraction. However, it is unclear whether detected bacteria originate from the breast capsule, breast glandular tissue or skin contamination. Moreover, this has never been investigated with molecular techniques. The aim of this study was to assess the bacterial microbiota on breast capsules, glandular tissue and skin using a highly sensitive PCR assay. MATERIALS AND METHODS: Fifty breast capsules were collected during implant removal or replacement. Ten specimens of glandular breast tissue and breast skin were collected in females who were undergoing reduction mammoplasty. A sample specimen (4 mm) was sterilely obtained from all tissues. All specimens were analysed by IS-pro, a 16S-23S interspace region-based PCR assay. RESULTS: Low numbers of Staphylococcus spp. (four species in four capsules) were found on breast capsules. There was no difference in bacterial presence between normal and contracted capsules. The skin of the breast-harboured Streptococcus spp. and Staphylococcus spp. while the glandular tissue was sterile. CONCLUSION: The low numbers of bacteria found on the capsules are most likely caused by contamination during capsule removal. More and larger studies are needed to investigate the bacterial presence on breast capsules using a PCR assay. This is the first study in which breast capsules have been studied using a highly sensitive PCR assay. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Contratura Capsular em Implantes/microbiologia , Reação em Cadeia da Polimerase/métodos , Infecções Relacionadas à Prótese/microbiologia , Centros Médicos Acadêmicos , Adulto , Implante Mamário/métodos , Implantes de Mama/microbiologia , Estudos Transversais , DNA Bacteriano/análise , Remoção de Dispositivo , Feminino , Seguimentos , Humanos , Contratura Capsular em Implantes/cirurgia , Microbiota , Pessoa de Meia-Idade , Países Baixos , Infecções Relacionadas à Prótese/epidemiologia , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.
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Antineoplásicos/economia , Medicamentos Genéricos/economia , Neoplasias Pulmonares/economia , Linfoma/economia , Antineoplásicos/uso terapêutico , Cetuximab/economia , Cetuximab/uso terapêutico , Cisplatino/economia , Cisplatino/uso terapêutico , Análise Custo-Benefício , Citarabina/economia , Citarabina/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Desoxicitidina/uso terapêutico , Dexametasona/economia , Dexametasona/uso terapêutico , Custos de Medicamentos , Medicamentos Genéricos/uso terapêutico , Cloridrato de Erlotinib/economia , Cloridrato de Erlotinib/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfoma/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Vinorelbina/economia , Vinorelbina/uso terapêutico , GencitabinaRESUMO
OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Arctostaphylos/química , Terapias Complementares/métodos , Ibuprofeno/uso terapêutico , Extratos Vegetais/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Doença Aguda/terapia , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Atenção Primária à Saúde , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
BACKGROUND: Silicone breast implants have been used for decades for cosmetic breast augmentation or reconstruction after mastectomy. In selected cases, postmastectomy adjuvant radiotherapy is given with the breast implants in situ. Previous clinical studies have shown that radiotherapy may lead to complications such as capsular contracture and infection and that removal of the implant may be required. Yet, the effect of radiotherapy on silicone breast implants themselves is unknown. The aim of this study was to investigate if irradiation of breast implants influences their mechanical properties. METHODS: This was an ex vivo study on 32 ready-to-use silicone breast implants (Mentor and Silimed). Half of the implants of each brand were irradiated with 1 × 60 Gy, the other half were not irradiated. Tensile, mechanical hysteresis, and rheology tests were performed. Differences in mechanical properties between the irradiated and nonirradiated implants were determined. RESULTS: No significant differences were found in tensile strength, mechanical hysteresis, and rheological properties between irradiated and nonirradiated implants. CONCLUSIONS: Breast implants' mechanical properties for these 2 brands were not significantly affected after single-dose irradiation in an ex vivo setting.
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BACKGROUND: Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. AIMS: To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. METHODS: This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100 µg/L, 100-300 µg/L and >300 µg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. RESULTS: Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6 years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100 µg/L, 100-300 µg/L and >300 µg/L for liver-related as well as all-cause mortality (P < 0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P < 0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P = 0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). CONCLUSION: Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.