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Background: Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Methods: Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. Results: In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Conclusions: Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.
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Carcinoma Pulmonar de Células não Pequenas , Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doença Crônica , Preparações FarmacêuticasRESUMO
INTRODUCTION: Diagnosis and treatment of obstructive sleep apnea (OSA) in children is often delayed due to the high prevalence and limited physician and sleep testing resources. As a result, children may be referred to multiple specialties, such as pediatric sleep medicine and pediatric otolaryngology, resulting in long waitlists. METHOD: We used data from our pediatric OSA clinic to identify predictors of tonsillectomy and/or adenoidectomy (AT). Before being seen in the clinic, parents completed the Pediatric Sleep Questionnaire (PSQ) and screening questionnaires for restless leg syndrome (RLS), nasal rhinitis, and gastroesophageal reflux disease (GERD). Tonsil size data were obtained from patient charts and graded using the Brodsky-five grade scale. Children completed an overnight oximetry study before being seen in the clinic, and a McGill oximetry score (MOS) was assigned based on the number and depth of oxygen desaturations. Logistic regression, controlling for otolaryngology physician, was used to identify significant predictors of AT. Three triage algorithms were subsequently generated based on the univariate and multivariate results to predict AT. RESULTS: From the OSA cohort, there were 469 eligible children (47% female, mean age = 8.19 years, SD = 3.59), with 89% of children reported snoring. Significant predictors of AT in univariate analysis included tonsil size and four PSQ questions, (1) struggles to breathe at night, (2) apneas, (3) daytime mouth breathing, and (4) AM dry mouth. The first triage algorithm, only using the four PSQ questions, had an odds ratio (OR) of 4.02 for predicting AT (sensitivity = 0.28, specificity = 0.91). Using only tonsil size, the second algorithm had an OR to predict AT of 9.11 (sensitivity = 0.72, specificity = 0.78). The third algorithm, where MOS was used to stratify risk for AT among those children with 2+ tonsils, had the same OR, sensitivity, and specificity as the tonsil-only algorithm. CONCLUSION: Tonsil size was the strongest predictor of AT, while oximetry helped stratify individual risk for AT. We recommend that referral letters for snoring children include graded tonsil size to aid in the triage based on our findings. Children with 2+ tonsil sizes should be triaged to otolaryngology, while the remainder should be referred to a pediatric sleep specialist.
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Apneia Obstrutiva do Sono , Tonsilectomia , Adenoidectomia , Algoritmos , Criança , Feminino , Humanos , Masculino , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/cirurgia , TriagemRESUMO
Long-term pharyngeal dysphagia is a common complication following head and neck cancer (HNC) therapies. High-level evidence for pharyngoesophageal junction (POJ) dilatation as a treatment in this population is lacking. We aimed to evaluate the safety and efficacy of POJ dilatation in dysphagic HNC survivors. This single-center, single-blind, placebo-controlled trial (St George Hospital, Sydney, Australia) randomly assigned (1:1) HNC survivors with long-term dysphagia (≥12 months postcompleted HNC therapies) to receive either graded endoscopic dilatations or sham dilatation (placebo). Patients were blinded to intervention types. Two strata were used for permuted randomization: (1) HNC therapies (total laryngectomy vs. chemoradiation alone); (2) Prior POJ dilatation (nil vs. previous dilatation). The primary endpoint was a short-term clinical response in swallowing function (3 months), defined as (1) a decrease in Sydney Swallow Questionnaire score by ≥200 or a score ≤ ULN; and (2) satisfactory global clinical assessment. The secondary endpoints were dysphagia relapse and serious adverse events. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000707369). Between 13 January 2013 and 16 January 2017, 41 patients were randomly assigned to endoscopic dilatation (n = 21) or placebo (n = 20). The short-term response rate in the endoscopic dilatation group was 76% (n = 16), compared with 5% (n = 1) in the placebo group (P < 0.001). There were no serious adverse events. The finding of a mucosal tear postdilatation was associated strongly with clinical response (OR 13.4, 95% CI [2.4, 74.9], P = 0.003). Kaplan-Meier estimate of dysphagia relapse is 50% by 9.6 months (95% CI [6.0, 19.2]) from completion of dilatation. Endoscopic dilatation of the POJ is a safe and efficacious therapy for the treatment of long-term dysphagia in HNC survivors. Close follow-up and repeat dilatation are necessary given the high dysphagia relapse rate.
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Transtornos de Deglutição/terapia , Deglutição , Dilatação/métodos , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/efeitos adversos , Doença Crônica , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Dilatação/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Lacerações/etiologia , Laringectomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mucosa/lesões , Estudos Prospectivos , Recidiva , Método Simples-Cego , Inquéritos e Questionários , Fatores de TempoRESUMO
INTRODUCTION: Restrictive defects of the pharyngo-esophageal junction (PEJ) are common in both structural and neurological disorders and are amenable to therapies aiming to reduce outflow resistance. Intrabolus pressure (IBP) acquired with high-resolution manometry and impedance (HRMI) is an indicator of resistance and a marker of reduced PEJ compliance. Constraints and limitations of IBP as well as the optimal IBP parameter remain undefined. AIMS: To determine: (i) the impact of peak pharyngeal pressure (PeakP) on the diagnostic accuracy of IBP for the detection of a restrictive defect at the PEJ and (ii) the optimal IBP parameter for this purpose. METHODS: In 52 dysphagic patients previously treated for head and neck cancer. Five candidate IBP measures and PeakP were obtained with HRMI, as well as a presence of a stricture determined by a mucosal tear after endoscopic dilatation. Predictive values of IBP measures were evaluated by receiver operating characteristic (ROC) analysis for all patients and reiterated as patients with lowest PeakP were progressively removed from the cohort. RESULTS: All IBP parameters had fair to good accuracy at predicting strictures. Intrabolus pressure measured at a discrete point of maximum admittance 1 cm above the maximal excursion of the upper esophageal sphincter had highest sensitivity (0.76) and specificity (0.78). When PeakP was at least 57 mm Hg both sensitivity and specificity improved to 0.9. CONCLUSIONS: Pharyngeal propulsive force has substantial impact on the accuracy of IBP as a predictor of a PEJ stricture. When PeakP is ≥57 mm Hg, an elevated IBP is highly predictive of a restrictive defect at the PEJ.
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Transtornos de Deglutição/diagnóstico , Esfíncter Esofágico Superior/fisiopatologia , Estenose Esofágica/diagnóstico , Manometria/métodos , Idoso , Antineoplásicos/efeitos adversos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Impedância Elétrica , Estenose Esofágica/etiologia , Estenose Esofágica/fisiopatologia , Feminino , Humanos , Laringectomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Faringe/fisiopatologia , Radioterapia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
OBJECTIVE: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma. METHODS: We used an adherence-exposure-outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration-time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios. RESULTS: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus. CONCLUSION: Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS.
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AIMS: The increasing use of highly conformal radiation techniques to treat meningioma confers a greater need for accurate targeting. Several groups have shown that positron emission tomography/computed tomography (PET/CT) information alters meningioma targets contoured by single observers, but whether this translates into improved accuracy has not been defined. As magnetic resonance imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous PET/MRI may be superior to PET/CT. We assessed whether 68Ga DOTATATE PET imaging (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma target volume contouring. MATERIALS AND METHODS: Ten patients with meningioma underwent simultaneous 68Ga DOTATATE PET/MRI followed by PET/CT. They were selected as it was anticipated that target volume definition in their cases would be particularly challenging. Three radiation oncologists contoured target volumes according to an agreed protocol: gross tumour volume (GTV) and clinical target volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative differences between PET(CT) and PET(MRI) were evaluated. RESULTS: There was substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38, CT/MRI+PET(MRI) 0.39 (P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35, CT/MRI+PET(MRI) 0.35 (P = 0.04 for all groups; P > 0.05 for individual pairs). One observer consistently contoured largest and one smallest. Observers rarely decreased volumes in relation to PET. Most IOV occurred in bone followed by dural tail, postoperative bed and venous sinuses. Tumour edges were qualitatively clearer on PET(MRI) versus PET(CT), but this did not affect contouring. CONCLUSION: IOV in contouring challenging meningioma cases was large and only slightly improved with the addition of 68Ga DOTATATE PET. Simultaneous PET/MRI for meningioma contouring is feasible, but did not improve IOV versus PET/CT. Whether volumes can be safely reduced according to PET requires evaluation.
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Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/radioterapia , Compostos Organometálicos/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Conformacional/métodos , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Variações Dependentes do Observador , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). METHODS: This cohort study included children 8-12â years of age who were born EP (≤28â weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36â weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36â weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. RESULTS: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18±5% and -14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. CONCLUSIONS: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD.
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Displasia Broncopulmonar/fisiopatologia , Exercício Físico/fisiologia , Lactente Extremamente Prematuro/fisiologia , Mecânica Respiratória/fisiologia , Canadá , Criança , Teste de Esforço , Feminino , Humanos , Masculino , Testes de Função RespiratóriaRESUMO
BACKGROUND: Pharyngeal automated impedance manometry (AIM) analysis is a novel non-radiological method to analyze swallowing function based on impedance-pressure recordings. In dysphagic head and neck cancer patients, we evaluated the reliability and validity of the AIM-derived swallow risk index (SRI) and a novel measure of postswallow residue (iZn/Z) by comparing it against videofluoroscopy as the gold standard. METHODS: Three blinded experts classified 88 videofluoroscopic swallows from 16 patients for aspiration and degree of postswallow residue. Pressure-impedance recordings of the patient and age-matched control swallows were analyzed using AIM by three observers who derived the SRI and iZn/Z. Intra-class correlation coefficients (ICC) were calculated for videofluoroscopic and AIM measures. Patient pressure/impedance measurements were compared with videofluoroscopy scores and control subjects to determine validity for detecting clinically relevant swallowing dysfunction. KEY RESULTS: Agreement among observers assessing presence of penetration and aspiration was modest (ICC 0.57) for videofluoroscopy and good (ICC 0.71, 0.82) for AIM-derived SRI and iZn/Z. When compared with age-matched controls, the SRI was higher in patients with aspiration (mean diff. 28.6, 95% CI [55.85, 1.355], p < 0.05). The iZn/Z had moderate positive correlation with bolus residue on fluoroscopy (BRS score) (rs (86) = 0.4120, p < 0.0001) and was increased in both patients with aspiration (∆244 [419.7, 69.52; p < 0.05]) and penetration (∆240 [394.3, 85.77]; p < 0.05) compared to controls. CONCLUSIONS & INFERENCES: AIM-based measures of swallowing function have better inter-rater reliability than comparable fluoroscopically derived measures. These measures are easily determined and objective markers of clinically relevant features of disordered swallowing following radiotherapy.
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Transtornos de Deglutição/diagnóstico , Fluoroscopia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Manometria/métodos , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Impedância Elétrica , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
Type II endometrial carcinomas (ECs) are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. As TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1(d/d)Trp53(d/d)) clearly demonstrate architectural features characteristic of type II ECs, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6 months of age. Further, Cdh1(d/d)Trp53(d/d) tumors in 12-month-old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphological intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1(d/d)Trp53(d/d) mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1(d/d)Trp53(d/d) mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1(d/d)Trp53(d/d) mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1(d/d)Trp53(d/d) uteri. Further, inflammatory mediators secreted from CDH1-negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory-related genes through activation of nuclear factor-κB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages and promotes aggressive ECs.
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Proteínas Cdh1/genética , Neoplasias do Endométrio/genética , Inflamação/genética , Macrófagos/imunologia , Proteína Supressora de Tumor p53/genética , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Arginase/genética , Linhagem Celular , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Neovascularização Patológica/genética , Receptores de Superfície Celular/genética , Microambiente Tumoral/imunologia , Útero/citologia , Útero/patologiaRESUMO
AIMS: Dysphagia is a well-recognised acute complication after radiotherapy. However, knowledge about the long-term prevalence and effect remains limited. The aims of this study were to determine the prevalence, severity, morbidity, time course and reporting patterns of dysphagia symptoms after head and neck radiotherapy. MATERIALS AND METHODS: An observational cross-sectional study was conducted in a large consecutive series of head and neck cancer patients. All patients in the St George Hospital Cancer Care database who had received head and neck radiotherapy with curative intent 0.5-8 years previously and recorded as being alive were surveyed using the Sydney Swallow Questionnaire (SSQ). Case notes were reviewed to determine the level of awareness of swallowing dysfunction in all patients, as well as the causes of mortality in the 83 deceased patients. RESULTS: The mean follow-up at the time of survey was 3 years after radiotherapy (range 0.5-8 years). Of the 116 patients surveyed by questionnaire, the response rate was 72% (83). Impaired swallowing (SSQ score > 234) was reported by 59% of patients. Dysphagia severity was not predicted by tumour site or stage, nor by the time since therapy, age, gender or adjuvant chemotherapy. Review of the hospital medical records and cancer database revealed that cancer accounted for 55% of deaths and aspiration pneumonia was responsible for 19% of non-cancer-related deaths. Of those with abnormal SSQ scores, only 47% reported dysphagia during follow-up clinic visits. CONCLUSIONS: Persistent dysphagia is a prevalent, under-recognised and under-reported long-term complication of head and neck radiotherapy which currently cannot be predicted on the basis of patient, tumour or treatment characteristics. Aspiration pneumonia is an important contributor to non-cancer-related mortality in these patients. These data highlight the need for closer monitoring of swallow dysfunction and its sequelae in this population.
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Transtornos de Deglutição/mortalidade , Deglutição , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/mortalidade , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Transversais , Transtornos de Deglutição/etiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Meningiomas are the most common primary intracranial tumour. Although external beam radiotherapy and radiosurgery are well-established treatments, affording local control rates of 85-95% at 10 years, the evidence base is mainly limited to single institution case series. This has resulted in inconsistent practices. It is generally agreed that radiotherapy is an established primary therapy in patients requiring treatment for surgically inaccessible disease and postoperatively for grade 3 tumours. Controversy exists surrounding whether radiotherapy should be upfront or reserved for progression for incompletely excised and grade 2 tumours. External beam radiotherapy and radiosurgery have not been directly compared, but seem to offer comparable rates of control for benign disease. Target volume definition remains contentious, including the inclusion of hyperostotic bone, dural tail and surrounding brain, but pathological studies are shedding some light. Most agree that doses around 50-54 Gy are appropriate for benign meningiomas and ongoing European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group studies are evaluating dose escalation for higher risk disease. Here we address the 'who, when and how' of radiotherapy for meningioma.
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Neoplasias Encefálicas/cirurgia , Meningioma/radioterapia , Meningioma/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Humanos , Meningioma/patologia , Gradação de Tumores , Radiocirurgia/métodos , Resultado do TratamentoRESUMO
Assessments of the medical and economic value of therapies in diseases such as cancer traditionally focus on average or median gains in patients' survival. This focus ignores the value that patients may place on a therapy with a wider "spread" of outcomes that offer the potential of a longer period of survival. We call such treatments "hopeful gambles" and contrast them with "safe bets" that offer similar average survival but less chance of a large gain. Real-world therapy options do not have these stylized forms, but they can differ in the spread of survival gains that patients face. We found that 77 percent of surveyed cancer patients with melanoma, breast cancer, or other kinds of solid tumors preferred hopeful gambles to safe bets. This suggests that current technology assessments, which often determine access to such cancer therapies, may be missing an important source of value to patients and should either incorporate hope into the value of therapies or set a higher threshold for an acceptable cost-effectiveness ratio in the end-of-life context.
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Neoplasias/tratamento farmacológico , Neoplasias/economia , Preferência do Paciente/psicologia , Idoso , Análise Custo-Benefício , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
There is a growing emphasis on promoting medical treatments that provide the most benefits relative to their costs. However, objective criteria for determining the value patients receive from treatment are lacking. This study used data on the treatment choices of terminally ill patients to estimate the value they associate with care. We found that patients place high valuations on metastatic cancer therapy--on average, twenty-three times higher than its cost--and that other traditional methods used to estimate the value of these treatments for patients significantly undervalues how patients view them. Our methods provide another framework for an evidence-based approach to assessing the value of treatments for terminal illness.
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Metástase Neoplásica/tratamento farmacológico , Preferência do Paciente , Idoso , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Doente Terminal , Estados UnidosRESUMO
BACKGROUND: The Ponseti method has become increasingly popular in the treatment of congenital talipes equinovarus (CTEV). Current methods of assessment focus on clinical, functional and radiological outcomes which are subjective and often difficult to repeat. However, integration of biomechanical evaluation can provide objective and quantifiable analysis. This study aims to evaluate the treatment outcome of CTEV patients on the basis of long-term clinical, functional and biomechanical assessment. METHODS: Following treatment, five children with CTEV were reviewed annually for the period 2008-2010. Clinical and functional outcomes were graded using parental questionnaires and clinical examination. Biomechanical parameters were evaluated using digital foot pressure studies. RESULTS: The study group recorded good clinical and functional outcomes. However, biomechanical studies have been able to identify subtle abnormalities that would be unapparent otherwise on clinical examination. CONCLUSIONS: It is recommended that biomechanical assessment be integrated into the overall evaluation of the outcome of CTEV after treatment.
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Pé Torto Equinovaro/cirurgia , Pé/fisiopatologia , Procedimentos Ortopédicos/métodos , Postura , Fenômenos Biomecânicos , Pré-Escolar , Pé Torto Equinovaro/diagnóstico , Pé Torto Equinovaro/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pressão , Fatores de TempoRESUMO
Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk-prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23,575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1-5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre- and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end-stage kidney disease. The risk-prediction equations performed well, with the time-dependent c-statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant-related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation.
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Doença das Coronárias/etiologia , Transplante de Rim/efeitos adversos , Adulto , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , Doença das Coronárias/induzido quimicamente , Doença das Coronárias/epidemiologia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/etiologia , Incidência , Rim , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/complicações , Falência Renal Crônica/etiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fatores de RiscoRESUMO
BACKGROUND: Inappropriate or excessive, non-swallow related, reflexive relaxation of the upper esophageal sphincter (UES) in response to esophageal distension may be the principal mechanism permitting retrograde trans-sphincteric flow during acid regurgitation. The neural pathways mediating reflexive UES relaxation in the human have received little attention. Patients with laryngitis demonstrate an increased acid reflux in the proximal esophagus. Such events, combined with an increased tendency for UES relaxation, might precipitate regurgitation into the pharynx. The aim was to determine whether the esophago-UES relaxation reflex induced by rapid esophageal distension is upregulated in patients with posterior laryngitis. METHODS: In 21 healthy volunteers and 14 patients with posterior laryngitis, UES responses to rapid air insufflation were examined. UES responses were monitored with perfused manometry catheter with a oval sleeve sensor. KEY RESULTS: The probability of triggering UES relaxation in response to the rapid esophageal air distension, for all volumes of insufflation, was higher in laryngitis (45%) than in health (17%). The minimum distension volume required to elicit an UES relaxation response was significantly lower in laryngitis patients when compared with controls. Patients who demonstrated a laryngoscopic response to a trial of omeprazole, were less likely to generate a distension-induced UES contractile response (5%) than patients who did not respond (23%). CONCLUSIONS & INFERENCES: The threshold for esophageal distension-induced UES relaxation is reduced in patients with laryngitis when compared with controls. This finding supports the hypothesis that in this population, a hypersensitive belch-like response may be one contributory mechanism of regurgitation when triggered by an abrupt spontaneous gastro-esophageal reflux event.
Assuntos
Esfíncter Esofágico Superior/fisiopatologia , Esôfago/fisiopatologia , Refluxo Laringofaríngeo/fisiopatologia , Relaxamento Muscular/fisiologia , Adulto , Idoso , Antiulcerosos/uso terapêutico , Feminino , Humanos , Refluxo Laringofaríngeo/tratamento farmacológico , Laringoscopia , Masculino , Manometria , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Seleção de Pacientes , Peristaltismo/fisiologia , Faringe/fisiopatologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: The objective of this study was to explore the prevalence, range of reported symptoms, and clinical risk factors of obstructive sleep apnea in preschool children with cleft lip and/or palate. DESIGN: Questionnaires were distributed to parents/guardians of all children from birth to 5 years of age who were followed by the cleft clinic. RESULTS: Questionnaire data and cleft classification were available for 248 children, with a mean age of 33.4 months. Obstructive sleep apnea was identified in 31.4% of the children. Only 29.5% of children with obstructive sleep apnea had undergone an investigation of these symptoms. The three most common symptoms reported in children with a questionnaire diagnosis of obstructive sleep apnea were (1) "heavy or loud breathing," (2) "easily distracted," and (3) "on the go" or "driven by a motor." The only clinical risk factor associated with a questionnaire diagnosis of obstructive sleep apnea was the presence of a syndrome (chi(2) = 3.5, p = .05). There were no significant differences in risk of obstructive sleep apnea by age, cleft classification, and surgical status. CONCLUSION: Preschool children with cleft lip and/or palate have a risk of obstructive sleep apnea that is as much as five times that of children without cleft. Obstructive sleep apnea appears to be underrecognized in this group of children. Further research is needed to investigate important risk factors for obstructive sleep apnea in children with cleft lip and/or palate.
Assuntos
Fissura Palatina/epidemiologia , Programas de Rastreamento , Apneia Obstrutiva do Sono/epidemiologia , Atenção/fisiologia , Comportamento Infantil , Pré-Escolar , Fenda Labial/classificação , Fenda Labial/epidemiologia , Fissura Palatina/classificação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Atividade Motora/fisiologia , New South Wales/epidemiologia , Polissonografia , Prevalência , Sons Respiratórios , Fatores de Risco , Inquéritos e Questionários , SíndromeRESUMO
UNLABELLED: Deglutition disorders (dysphagia) are common following total laryngectomy. As the aetiology of the disorder is poorly understood, its incidence is probably under-estimated. Dysphagia may result from many factors, including the type of laryngectomy surgery employed and the use of adjuvant treatments (e.g. radiotherapy and chemotherapy). Dysphagia may also be compounded by other co-morbid factors, such as ageing and depression. AIM: To investigate the methods of surgical closure used by Australian ENT and head and neck surgeons after undertaking total laryngectomy surgery. METHOD: In order to audit surgical variation, 56 short questionnaires were sent to all Australian ENT and head and neck surgeons who were registered members of the Australia and New Zealand Head and Neck Society. Twenty-eight questionnaires (50 per cent) were completed and returned. RESULTS: Respondents reported using a variety of different reconstructive methods after total laryngectomy surgery. Specifically, there were differences in the type and levels of pharyngeal closure employed and the suturing techniques used. CONCLUSION: Currently, there is no scientific evidence to direct surgeons to the optimal pharyngeal reconstruction technique(s) ensuring for good swallowing results post-laryngectomy. An analysis of the effect of surgical reconstruction technique on laryngectomees' post-operative swallowing ability is needed, in order to provide evidence to determine optimal surgical techniques.
Assuntos
Transtornos de Deglutição/etiologia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Procedimentos Cirúrgicos Otorrinolaringológicos/normas , Austrália , Terapia Combinada , Feminino , Humanos , Laringectomia/reabilitação , Masculino , Período Pós-Operatório , Padrões de Prática Médica , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
AIM: The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). METHODS: Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of 'in-person' meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. RESULTS: Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. CONCLUSION: Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard 'in-person' meetings.
Assuntos
Neoplasias da Mama/terapia , Tomada de Decisões , Telemedicina/estatística & dados numéricos , Atitude do Pessoal de Saúde , Neoplasias da Mama/economia , Comportamento do Consumidor , Custos e Análise de Custo , Feminino , Hospitais de Distrito , Humanos , Equipe de Assistência ao Paciente , Saúde da População Rural , Escócia , Telemedicina/economia , Resultado do TratamentoRESUMO
Virus-like particle-based vaccines for high-risk human papillomaviruses (HPVs) appear to have great promise; however, cell culture-derived vaccines will probably be very expensive. The optimization of expression of different codon-optimized versions of the HPV-16 L1 capsid protein gene in plants has been explored by means of transient expression from a novel suite of Agrobacterium tumefaciens binary expression vectors, which allow targeting of recombinant protein to the cytoplasm, endoplasmic reticulum (ER) or chloroplasts. A gene resynthesized to reflect human codon usage expresses better than the native gene, which expresses better than a plant-optimized gene. Moreover, chloroplast localization allows significantly higher levels of accumulation of L1 protein than does cytoplasmic localization, whilst ER retention was least successful. High levels of L1 (>17% total soluble protein) could be produced via transient expression: the protein assembled into higher-order structures visible by electron microscopy, and a concentrated extract was highly immunogenic in mice after subcutaneous injection and elicited high-titre neutralizing antibodies. Transgenic tobacco plants expressing a human codon-optimized gene linked to a chloroplast-targeting signal expressed L1 at levels up to 11% of the total soluble protein. These are the highest levels of HPV L1 expression reported for plants: these results, and the excellent immunogenicity of the product, significantly improve the prospects of making a conventional HPV vaccine by this means.