Theoretical analysis of a contactless transportation system for cylindrical objects based on ultrasonic levitation.

Contactless transportation systems based on near-field acoustic levitation have the benefit of compact design and easy control which are able to meet the cleanliness and precision demands required in precision manufacturing. However, the problems involved in contactless positioning and transporting cylindrical objects have not yet been addressed. This paper introduces a contactless transportation system for cylindrical objects based on grooved radiators. A groove on the concave surface of the radiator produces an asymmetrical pressure distribution which results in a thrusting force to drive the levitator horizontal movement. The pressure distribution between the levitator and the radiator is acquired by solving the Reynolds equation. The levitation and the thrusting forces are obtained by integrating the pressure and the pressure gradient over the concave surface, respectively. The predicted results of the levitation force agree well with experimental observations from the literature. Parameter studies show that the thrusting force increases and converges to a stable value as the groove depth increases. An optimal value for the groove arc length is found to maximize the thrusting force, and the thrusting force increases as the groove width, the radiator vibration amplitude, and the levitator weight increase.

Measuring the proportion of time spent on work activities of clinical pharmacists using work sampling technique at a public hospital in Malaysia.

BACKGROUND: The clinical pharmacy service to the ward was established in 2005 in Malaysia, as the number of pharmacists working in the public service sector began to grow. Yet, there has been little local research done on reporting the range of work activities of clinical pharmacists and the amount of time that they spent on their work activities. OBJECTIVE: This study aimed to identify the range of work activities of clinical pharmacists by observation and to estimate the proportion of time spent on different work activities by using the work sampling technique. METHODS: The time spent by clinical pharmacists on various activities was measured using the work sampling technique over 30 working days. The work activities of clinical pharmacists were pre-identified and customized into an activity checklist. Two observers were placed at the study site and took turns recording the activities performed by the clinical pharmacists by following a randomly generated observation schedule. RESULTS: 1,455 observations were made on five clinical pharmacists with a total of 3493 events recorded. Overall, clinical pharmacists spent 78.8% (n=2751) of their time providing clinical services whereas 12.3% (n=433) of their time was spent on non-clinical activities. They were found to be idle from work for 8.9% of the time. There was no difference in bed occupancy rate in the study site regardless of the presence of the observer (p=0.384). Clinical pharmacists were found to report a higher average daily cumulative work unit of 9.8 (SD=4.3) when under observation compared to an average daily cumulative work unit of 6.5 (SD=4.6) when no observer was present (p=0.005). CONCLUSIONS: The results revealed that clinical pharmacists spent a significant amount of time on non-clinical work. Their responsibilities with non-clinical work should be properly taken care of so they can allocate more time to providing patient care.

Measuring the proportion of time spent on work activities of clinical pharmacists using work sampling technique at a public hospital in Malaysia

Background: The clinical pharmacy service to the ward was established in 2005 in Malaysia, as the number of pharmacists working in the public service sector began to grow. Yet, there has been little local research done on reporting the range of work activities of clinical pharmacists and the amount of time that they spent on their work activities. Objective: This study aimed to identify the range of work activities of clinical pharmacists by observation and to estimate the proportion of time spent on different work activities by using the work sampling technique. Methods: The time spent by clinical pharmacists on various activities was measured using the work sampling technique over 30 working days. The work activities of clinical pharmacists were pre-identified and customized into an activity checklist. Two observers were placed at the study site and took turns recording the activities performed by the clinical pharmacists by following a randomly generated observation schedule. Results: 1,455 observations were made on five clinical pharmacists with a total of 3493 events recorded. Overall, clinical pharmacists spent 78.8% (n=2751) of their time providing clinical services whereas 12.3% (n=433) of their time was spent on non-clinical activities. They were found to be idle from work for 8.9% of the time. There was no difference in bed occupancy rate in the study site regardless of the presence of the observer (p=0.384). Clinical pharmacists were found to report a higher average daily cumulative work unit of 9.8 (SD=4.3) when under observation compared to an average daily cumulative work unit of 6.5 (SD=4.6) when no observer was present (p=0.005). Conclusions: The results revealed that clinical pharmacists spent a significant amount of time on non-clinical work. Their responsibilities with non-clinical work should be properly taken care of so they can allocate more time to providing patient care (AU)

Chitosan as capping agent in a robust one-pot procedure for a magnetic catalyst synthesis.

Here, we report a one-pot solvothermal method for the development of magnetically recoverable catalysts with Ru or Ag nanoparticles (NPs) capped by chitosan (CS), a derivative of natural chitin. The formation of iron oxide NPs was carried out in situ in the presence of CS and iron acetylacetonate in boiling triethyleneglycol (TEG) due to CS solubilization in warm TEG. Coordination with Ru or Ag species and the NP formation take place in the same reaction solution, eliminating intermediate steps. In optimal conditions the method developed allows stabilization of 2.2 nm monodisperse Ru NPs (containing both Ru0 and Ru4+ species) that are evenly distributed through the catalyst, while for Ag NPs, this stabilizing medium is inferior, leading to exceptionally large Ag nanocrystals. Catalytic testing of CS-Ru magnetically recoverable catalysts in the reduction of 4-nitrophenol to 4-aminophenol with excess NaBH4 revealed that the catalyst with 2.2 nm Ru NPs exhibits the highest catalytic activity compared to samples with larger Ru NPs (2.9-3.2 nm). Moreover, this catalyst displayed extraordinary shelf-life in the aqueous solution (up to ten months) and excellent reusability in ten consecutive reactions with easy magnetic separation at each step which were assigned to its conformational rigidity at a constant pH. These characteristics as well as favorable environmental factors of the catalyst fabrication, make it promising for nitroarene reduction.

Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer Nanoparticle-Based Drug Delivery Platforms.

The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.

Stabilizing near-field acoustic levitation: Investigation of non-linear restoring force generated by asymmetric gas squeeze film.

The instability of a floating object is the main factor preventing near-field acoustic levitation (NAFL) from being widely used in the manufacture of micro-electro-mechanical systems. Therefore, investigating the restoring force due to the generation mechanisms of NAFL is necessary to ensure the stable levitation of the floating object. This study presents a theoretical analysis to evaluate the restoring force based on the gas-film-lubrication theory. The gas-film pressure between the reflector and the radiator is expressed in the form of the dimensionless Reynolds equation in a cylindrical coordinate system, which is solved by an eight-point discrete grid method due to the discontinuous gas-film distribution. An experimental rig is constructed to measure the restoring force at various eccentricities, which can be used to support the developed numerical model. The theoretical results show that the restoring force increases with an increment in eccentricity, which agrees with experimental results. Furthermore, theoretical prediction results indicate that the restoring force increases when the amplitude of the radiator and weight of the levitator increases, which indicates higher system stability. The results of the radiator vibration mode on the restoring force show that the restoring force is the largest in the first-order mode.

Evaluating lubricant performance to reduce COVID-19 PPE-related skin injury.

BACKGROUND: Healthcare workers around the world are experiencing skin injury due to the extended use of personal protective equipment (PPE) during the COVID-19 pandemic. These injuries are the result of high shear stresses acting on the skin, caused by friction with the PPE. This study aims to provide a practical lubricating solution for frontline medical staff working a 4+ hours shift wearing PPE. METHODS: A literature review into skin friction and skin lubrication was conducted to identify products and substances that can reduce friction. We evaluated the lubricating performance of commercially available products in vivo using a custom-built tribometer. FINDINGS: Most lubricants provide a strong initial friction reduction, but only few products provide lubrication that lasts for four hours. The response of skin to friction is a complex interplay between the lubricating properties and durability of the film deposited on the surface and the response of skin to the lubricating substance, which include epidermal absorption, occlusion, and water retention. INTERPRETATION: Talcum powder, a petrolatum-lanolin mixture, and a coconut oil-cocoa butter-beeswax mixture showed excellent long-lasting low friction. Moisturising the skin results in excessive friction, and the use of products that are aimed at 'moisturising without leaving a non-greasy feel' should be prevented. Most investigated dressings also demonstrate excellent performance.

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy.

Theranostics is a fast-growing field due to demands for new, efficient therapeutics which could be precisely delivered to the target site using multimodal imaging with enhancing auxiliary actions. In this review article we discuss theranostic nanoplatforms containing polymers and magnetic nanoparticles along with other components. Magnetic nanoparticles allow for both diagnostic and therapeutic (hyperthermia) capabilities, while polymers can be reservoirs for drugs and are easily functionalized for cell targeting. We focus on the most important design strategies to achieve optimal theranostic effects as well as the roles of different components included in theranostics, reviewing the literature from the last 5 years.

What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. Aim: The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Methods and results: Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. Conclusions: This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

Association of human papillomavirus and p16 status with mucositis and dysphagia for head and neck cancer patients treated with radiotherapy with or without cetuximab: Assessment from a phase 3 registration trial.

BACKGROUND: Mucositis and dysphagia are common adverse effects of radiotherapy (RT) treatment of locally advanced squamous cell cancer of the head and neck (LA-SCCHN). Chemotherapy added to RT increases survival rates but causes worse mucositis and dysphagia. The aim of this analysis was to assess the impact of p16 status on mucositis, dysphagia, and feeding tube use in LA-SCCHN among patients treated with RT±cetuximab in the phase 3 IMCL-9815 trial. METHODS: Patients received RT plus weekly cetuximab or RT alone. Subgroup analyses were conducted on patients with p16-positive (n=75) or p16-negative (n=106) oropharyngeal cancer (OPC), as determined by immunohistochemical analysis. The onset and duration of mucositis and dysphagia by treatment arm and p16 status were displayed using Kaplan-Meier curves and the log-rank test. P values for the incidence of mucositis and dysphagia were calculated using the Fisher exact test. Feeding tube use was assessed as the percent of patients reporting use. RESULTS: The baseline characteristics of patients treated with RT±cetuximab were similar in both the p16-positive and p16-negative OPC subgroups. Patients within the p16-positive OPC subgroup had higher Karnofsky scores and were more likely to have stage T1-T3 cancer and be from the United States. Regardless of p16 status, there was no difference in the onset or duration of grade 3/4 mucositis or dysphagia in patients receiving RT plus cetuximab compared with those receiving RT alone. In the overall population, and the p16-positive and p16-negative OPC subpopulations, feeding tube use was not different for patients receiving RT plus cetuximab compared with RT alone. CONCLUSION: Regardless of p16 status, the addition of cetuximab to RT did not alter the incidence, time to onset, severity, or duration of mucositis and dysphagia and did not impact the frequency of feeding tube use.

Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab.

PURPOSE: We conducted a retrospective evaluation of the IMCL-9815 study to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone. PATIENTS AND METHODS: In the IMCL-9815 study, patients were randomly allocated to receive RT plus weekly cetuximab or RT alone. A subpopulation of patients with p16-evaluable OPC was retrospectively evaluated on the basis of locoregional control (LRC), overall survival (OS), and progression-free survival (PFS). Evaluable samples from patients with p16-positive OPC were also tested for HPV DNA. RESULTS: Tumor p16 status was evaluable in 182 patients with OPC enrolled in the IMCL-9815 study; 41% were p16 positive. When treated with RT alone or RT plus cetuximab, p16-positive patients had a longer OS than p16-negative patients (hazard ratio, 0.40; 95% CI, 0.21 to 0.74 and hazard ratio, 0.16; 95% CI, 0.07 to 0.36, respectively). The addition of cetuximab to RT increased LRC, OS, and PFS in both patients with p16-positive OPC and those with p16-negative disease. Interaction tests for LRC, OS, and PFS did not demonstrate any significant interaction between p16 status and treatment effect (P = .087, .085, and .253, respectively). Similar trends were observed when patients with p16-positive/HPV-positive OPC (n = 49) and those with p16-positive/HPV-negative OPC (n = 14) were compared. CONCLUSION: p16 status was strongly prognostic for patients with OPC. The data suggest that the addition of cetuximab to RT improved clinical outcomes regardless of p16 or HPV status versus RT alone.

Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer.

PURPOSE: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. METHODS AND MATERIALS: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. RESULTS: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). CONCLUSIONS: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.

Radiation induces acute alterations in neuronal function.

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

Unilateral radiotherapy for the treatment of tonsil cancer.

PURPOSE: To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques that irradiate the involved tonsil region and ipsilateral neck only. METHODS AND MATERIALS: Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with <1 cm involvement of the soft palate. Patients had TX (n = 17 patients), T1 (n = 52), or T2 (n = 33) disease, with Nx (n = 3), N0 (n = 33), N1 (n = 23), N2a (n = 21), or N2b (n = 22) neck disease. RESULTS: Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease. CONCLUSIONS: Unilateral radiotherapy for patients with TX-T2, N0-N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity requiring gastrostomy.

Hyperfractionated or accelerated radiotherapy for head and neck cancer.

BACKGROUND: Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. OBJECTIVES: The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010. SELECTION CRITERIA: We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998. DATA COLLECTION AND ANALYSIS: We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality. MAIN RESULTS: We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). AUTHORS' CONCLUSIONS: Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.

Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions.

BACKGROUND: Contrast nephropathy (CIN) increases adverse clinical outcomes. We examine risks and clinical predictors of CIN in patients undergoing percutaneous coronary intervention (PCI) and effectiveness of prophylactic therapy. METHODS: A cohort of 8,798 patients who underwent PCI from May 2000 to April 2008 was enrolled. We divided patients into 3 groups. A: STEMI patient undergoing primary PCI; B: UA/NSTEMI patients undergoing early PCI; C: Patients without MI undergoing elective PCI. Pre-PCI saline hydration was given to group B and C if baseline glomerular filtration rate (GFR) <60 ml/min/1.73 m². RESULTS: Mean age was 57.4 years; 35.9% was diabetics. Incidence of CIN were 12.0%, 9.2%, and 4.5%, in group A, B and C (P = <0.0005). CIN correlated with higher mortality (15.5% vs. 1.3%, P < 0.0005) at 1 month. The important predictors of CIN were age >70, female gender, anemia, low systolic BP < 100 mmHg, high creatinine kinase level, abnormal LVEF, baseline renal impairment, MI and insulin dependent diabetes. Incidence of CIN in patients with GFR >60 were 8.2%, 9.2%, and 4.3% in group A, B, and C respectively (p < 0.0005). Incidence of CIN in patients with GFR = 30-60 were 19.1%, 4.5%, and 2.4% (p < 0.0005) and in patients with GFR < 30 were 34.4%, 40.0%, and 25.9% (p = 0.510). CONCLUSIONS: Pre-hydration prophylaxis was effective in preventing CIN in mild renal impaired patients (GFR 30-60) but are less so in more severely renal impaired patients (GFR < 30). STEMI patients undergoing primary PCI regardless of baseline GFR were at high risk. Accelerated prophylactic regime can be considered in this cohort.

National Cancer Database report on cancer of the head and neck: 10-year update.

BACKGROUND: We sought to examine the current state of cancer care for head and neck tumors in the United States. We therefore performed a retrospective, longitudinal study of the approximately 822,000 head and neck cancer cases included in the National Cancer Data Base (NCDB) for 1990 through 2004, representing approximately 75% of the estimated incident diagnoses in the United States. METHODS: All cases of head and neck cancer diagnosed and reported to the NCDB during this interval were reviewed, and descriptive statistics, grouped by disease and host factors, were analyzed over time and compared with a prior similar analysis done 10 years ago. RESULTS: Although many similarities persist, several major changes in head and neck cancer have occurred, most notably (1) a decrease in the number of the older-aged patients who have mucosally derived squamous cell carcinomas coupled with an increase in the number of younger-aged patients who have thyroid-origin adenocarcinomas and (2) a decrease in the use of radiation therapy alone for treatment in favor of chemotherapy enhanced radiation therapy. CONCLUSION: Head and neck cancers include a heterogeneous group of tumors whose precise composition changes over time and whose therapy evolves as well. The NCDB is well suited to capture this information and provide both an analysis of the current state of cancer care for head and neck tumors and a longitudinal view over time.

Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data.

BACKGROUND: The gold standard endpoint in randomised trials of locally advanced head and neck squamous-cell carcinoma (HNSCC) is overall survival. Our objective was to study whether duration of locoregional control or event-free survival (EFS) could be considered as surrogate endpoints to estimate the effect of radiotherapy and chemotherapy on overall survival. This would allow a reduction in the duration and cost of the development of new treatments. METHODS: Individual patient data from 104 trials (22 744 patients), with 116 treatment-control comparisons, from four meta-analyses on hyperfractionated or accelerated radiotherapy and concomitant, induction, or adjuvant chemotherapy were analysed. Duration of locoregional control was defined as the time from randomisation to the first locoregional event and EFS as the time to any first event (ie, locoregional relapse, distant recurrence, or death). At the individual level, a rank correlation coefficient between the surrogate endpoint and overall survival was used to assess surrogacy; at the trial level, a correlation coefficient R between treatment effects was used. FINDINGS: At the individual level, overall survival was more strongly correlated with EFS (range of correlations 0.82-0.90) than with locoregional control (0.65-0.76). For radiotherapy, treatment effects on both locoregional control and EFS were strongly correlated with those on overall survival (R=0.94 and 0.98, respectively). For chemotherapy, the correlations between treatment effects on EFS and overall survival were stronger than those between locoregional control and overall survival (range of R 0.79-0.93 vs 0.53-0.84, respectively). INTERPRETATION: EFS is a better correlate with overall survival than locoregional control and could be used as a surrogate for overall survival to assess the treatment effect of radiotherapy and chemotherapy in randomised trials of locally advanced HNSCC.