Patients with oral tumors. Part 2: Quality of life after treatment with resection prostheses. Resection prosthetics: evaluation of quality of life

In the present study, the oral health-related quality of life of 18 patients (13 men and 5 women) was evaluated using validated questionnaires as proposed by the European Organization of Research and Treatment of Cancer (EORTC). The patients belonged to a cohort of 48 patients, whose prosthetic treatment was performed during the years 2004-2007. In the course of tumor resection, 12 patients underwent graft surgery and 14 patients radiotherapy. One patient required a nasal epithesis since resection of the nose became necessary. Five patients underwent a full block resection of the mandible, and tumor resection in 3 patients resulted in a large oronasal communication. Prosthetic rehabilitation was performed in all patients, and the follow-up period with regular care covered a minimum of 3 years. Eleven patients received dental implants for better support and retention of the prostheses. In spite of compromised oral conditions, functional restrictions, and some difficulties with the prostheses, the answers to the questionnaire were quite positive. The majority judged their general health as good or even excellent. The subjective perception of the patients may contradict the objective view by the dentist. In fact, the individual patient's history and experience provide a better understanding of the impact of oral tumors on daily life. The overall assessment identified 4 items that were perceived as major problems by all patients: swallowing solid food, dry mouth, limited mouth opening, and appearance. Prosthetic rehabilitation has only a limited influence on such problems.

The effectiveness and safety of d,l-sotalol in the ambulatory treatment of atrial fibrillation and flutter

Data on short and long term efficacy and safety of d,l sotalol in patients with atrial fibrillation or atrial flutter is limited. The aims of this study were to (1) assess the antiarrhythmic efficacy of d,l sotalol maintaining normal sinus rhythm in patients with refractory atrial fibrillation or flutter, (2) evaluate the efficacy of d,l sotalol in preventing recurrences of paroxysmal atrial fibrillation or flutter, (3) evaluate the control of ventricular rate in patients with paroxysmal or refractory atrial fibrillation or flutter unsuccessfully treated with other antiarrhythmic agents, (4) determine predictors of efficacy (5) assess the safety of d,l sotalol in this setting. Two hundred patients with chronic or paroxysmal atrial fibrillation or atrial flutter or both, who had failed one to six previous antiarrhythmic drug trials were treated with d,l sotalol 80 to 440 mg/day orally. Fifty four percent was female, age 47 +/- 16 years (range 7-79), follow up period 7 +/- 7 months (range 1 to 14 months), 79% of patients had the arrhythmia for more than one year. The atrial fibrillation in 37.5% of patients was chronic and paroxysmal in 23.5. The atrial flutter was chronic in 31% of patients and paroxysmal in 8%. Eighty two percent of patients was in functional class I (NYHA) and 82% had cardiac heart disease: left atrial (LA) size 44 +/- 10 mm, right atrial (RA) size 37 +/- 7 mm and left ventricular ejection fraction (LVEF) 58 +/- 8%. Total success was achieved in 58% of patients (atrial fibrillation 40% and 18% in atrial flutter), partial success in 38% (atrial fibrillation in 18% and 20% in atrial flutter) and 4% of patients failure. It was p < 0.07 when compared total success vs partial success among atrial fibrillation and atrial flutter groups. Patients with cardiac heart disease responded worst (p = 0.10) to the drug than those without it, specially if the heart was dilated. We concluded that d,l sotalol has moderate efficacy to convert and maintain normal sinus rhythm, as well as it acts controlling paroxysmal relapses and ventricular heart rate.

Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models

Background: WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. Methods: We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. Findings: All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6—12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. Interpretation: The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. Funding: Bill & Melinda Gates Foundation, WHO.

Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update

Objectives: To update the 2006 systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy. Data sources: Literature searches were updated in electronic databases (n=3), conference proceedings (n=3), and Food and Drug Administration transcripts. Multiple sources (n=13) were searched for potential gray literature. A primary source for current survival evidence was a recently published individual patient data meta-analysis. In that meta-analysis, patient data were obtained from investigators for studies enrolling more than 50 patients per arm. Because those data constitute the most currently available data for this update, as well as the source for on-study (active treatment) mortality data, we limited inclusion in the current report to studies enrolling more than 50 patients per arm to avoid potential differential endpoint ascertainment in smaller studies. Review methods: Title and abstract screening was performed by one or two (to resolve uncertainty) reviewers; potentially included publications were reviewed in full text. Two or three (to resolve disagreements) reviewers assessed trial quality. Results were independently verified and pooled for outcomes of interest. The balance of benefits and harms was examined in a decision model. Results: We evaluated evidence from 5 trials directly comparing darbepoetin with epoetin, 41 trials comparing epoetin with control, and 8 trials comparing darbepoetin with control; 5 trials evaluated early versus late (delay until Hb ≤9 to 11 g/dL) treatment. Trials varied according to duration, tumor types, cancer therapy, trial quality, iron supplementation, baseline hemoglobin, ESA dosing frequency (and therefore amount per dose), and dose escalation. ESAs decreased the risk of transfusion (pooled relative risk [RR], 0.58; 95% confidence interval [CI], 0.53 to 0.64; I2 = 51%; 38 trials) without evidence of meaningful difference between epoetin and darbepoetin. Thromboembolic event rates were higher in ESA-treated patients (pooled RR, 1.51; 95% CI, 1.30 to 1.74; I2 = 0%; 37 trials) without difference between epoetin and darbepoetin. In 14 trials reporting the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale, the most common patient-reported outcome, scores decreased by −0.6 in control arms (95% CI, −6.4 to 5.2; I2 = 0%) and increased by 2.1 in ESA arms (95% CI, −3.9 to 8.1; I2 = 0%). There were fewer thromboembolic and on-study mortality adverse events when ESA treatment was delayed until baseline Hb was less than 10 g/dL, in keeping with current treatment practice, but the difference in effect from early treatment was not significant, and the evidence was limited and insufficient for conclusions. No evidence informed optimal duration of therapy. Mortality was increased during the on-study period (pooled hazard ratio [HR], 1.17; 95% CI, 1.04 to 1.31; I2 = 0%; 37 trials). There was one additional death for every 59 treated patients when the control arm on-study mortality was 10 percent and one additional death for every 588 treated patients when the control-arm on-study mortality was 1 percent. A cohort decision model yielded a consistent result—greater loss of life-years when control arm on-study mortality was higher. There was no discernible increase in mortality with ESA use over the longest available followup (pooled HR, 1.04; 95% CI, 0.99 to 1.10; I2 = 38%; 44 trials), but many trials did not include an overall survival endpoint and potential time-dependent confounding was not considered. Conclusions: Results of this update were consistent with the 2006 review. ESAs reduced the need for transfusions and increased the risk of thromboembolism. FACT-Fatigue scores were better with ESA use but the magnitude was less than the minimal clinically important difference. An increase in mortality accompanied the use of ESAs. An important unanswered question is whether dosing practices and overall ESA exposure might influence harms.

Evaluation of histological, serological and clinical changes in response to abatacept treatment of primary Sjögren's syndrome: A pilot study

Objectives To prospectively evaluate histopathologic, blood cellular, serological and clinical changes in response to abatacept treatment in patients with primary Sjögren's syndrome (pSS). Methods Blood, saliva and minor salivary gland biopsies were obtained before and after the last of 8 doses of abatacept in 11 pSS patients. The histologic data evaluated the number of lymphocytic foci and of B- and T-cell subtypes (CD20(+) , CD3(+) , CD4(+) , CD8(+) ). The numbers of FoxP3(+) regulatory T-cells were measured and the FoxP3 /CD 3 ratio was calculated. Histologic data were compared with results from peripheral blood and with changes in saliva secretion. Results The numbers of lymphocytic foci decreased significantly (p=0.041). Numbers of local FoxP3(+) T-cells decreased significantly in percentage of total lymphocytic infiltrates (p=0.037). In the peripheral blood B-cells increased (p=0.038). This was due to an expansion of the naïve B cell pool (p=0.034). When adjusting for disease duration, an increase was also noted for total lymphocytes (p=0.044) and for CD 4 cells (p=0.009). Gamma globulins decreased significantly (p=0.005), but IgG reduction did not reach significance. Adjusted for disease duration, saliva production increased significantly (p=0.029). Conclusions CTLA4-Ig treatment significantly reduces glandular inflammation in pSS, induces several celluar changes and increases saliva production. Remarkably, this increase in saliva production is significantly influenced by disease duration.

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures

With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years. The Radiological Physics Center monitors sites involved in clinical trials through the use of site visits and remote auditing with thermoluminescent dosimeters (TLD) and mailable anthropomorphic phantoms. Currently, there are no heterogeneous phantoms that have been commissioned to evaluate proton therapy. It was hypothesized that an anthropomorphic pelvis phantom can be designed to audit treatment procedures (patient simulation, treatment planning and treatment delivery) at proton facilities to confirm agreement between the measured dose and calculated dose within 5%/3mm with a reproducibility of 3%. A pelvis phantom originally designed for use with photon treatments was retrofitted for use in proton therapy. The relative stopping power (SP) of each phantom material was measured. Hounsfield Units (HU) for each phantom material were measured with a CT scanner and compared to the relative stopping power calibration curve. The tissue equivalency for each material was calculated. Two proton treatment plans were created; one which did not correct for material SP differences (Plan 1) and one plan which did correct for SP differences (Plan 2). Film and TLD were loaded into the phantom and the phantom was irradiated 3 times per plan. The measured values were compared to the HU-SP calibration curve and it was found that the stopping powers for the materials could be underestimated by 5-10%. Plan 1 passed the criteria for the TLD and film margins with reproducibility under 3% between the 3 trials. Plan 2 failed because the right-left film dose profile average displacement was -9.0 mm on the left side and 6.0 mm on the right side. Plan 2 was intended to improve the agreements and instead introduced large displacements along the path of the beam. Plan 2 more closely represented the actual phantom composition with corrected stopping powers and should have shown an agreement between the measured and calculated dose within 5%/3mm. The hypothesis was rejected and the pelvis phantom was found to be not suitable to evaluate proton therapy treatment procedures.

Cost-effectiveness of universal prophylaxis in pregnancy with prior group B streptococci colonization.

OBJECTIVE: To estimate the costs and outcomes of rescreening for group B streptococci (GBS) compared to universal treatment of term women with history of GBS colonization in a previous pregnancy. STUDY DESIGN: A decision analysis model was used to compare costs and outcomes. Total cost included the costs of screening, intrapartum antibiotic prophylaxis (IAP), treatment for maternal anaphylaxis and death, evaluation of well infants whose mothers received IAP, and total costs for treatment of term neonatal early onset GBS sepsis. RESULTS: When compared to screening and treating, universal treatment results in more women treated per GBS case prevented (155 versus 67) and prevents more cases of early onset GBS (1732 versus 1700) and neonatal deaths (52 versus 51) at a lower cost per case prevented ($8,805 versus $12,710). CONCLUSION: Universal treatment of term pregnancies with a history of previous GBS colonization is more cost-effective than the strategy of screening and treating based on positive culture results.

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

EVALUATION OF INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY ERROR DUE TO IMRT TREATMENT PLAN COMPLEXITY AND IMPROPERLY MATCHED DOSIMETRY DATA

Intensity modulated radiation therapy (IMRT) is a technique that delivers a highly conformal dose distribution to a target volume while attempting to maximally spare the surrounding normal tissues. IMRT is a common treatment modality used for treating head and neck (H&N) cancers, and the presence of many critical structures in this region requires accurate treatment delivery. The Radiological Physics Center (RPC) acts as both a remote and on-site quality assurance agency that credentials institutions participating in clinical trials. To date, about 30% of all IMRT participants have failed the RPC’s remote audit using the IMRT H&N phantom. The purpose of this project is to evaluate possible causes of H&N IMRT delivery errors observed by the RPC, specifically IMRT treatment plan complexity and the use of improper dosimetry data from machines that were thought to be matched but in reality were not. Eight H&N IMRT plans with a range of complexity defined by total MU (1460-3466), number of segments (54-225), and modulation complexity scores (MCS) (0.181-0.609) were created in Pinnacle v.8m. These plans were delivered to the RPC’s H&N phantom on a single Varian Clinac. One of the IMRT plans (1851 MU, 88 segments, and MCS=0.469) was equivalent to the median H&N plan from 130 previous RPC H&N phantom irradiations. This average IMRT plan was also delivered on four matched Varian Clinac machines and the dose distribution calculated using a different 6MV beam model. Radiochromic film and TLD within the phantom were used to analyze the dose profiles and absolute doses, respectively. The measured and calculated were compared to evaluate the dosimetric accuracy. All deliveries met the RPC acceptance criteria of ±7% absolute dose difference and 4 mm distance-to-agreement (DTA). Additionally, gamma index analysis was performed for all deliveries using a ±7%/4mm and ±5%/3mm criteria. Increasing the treatment plan complexity by varying the MU, number of segments, or varying the MCS resulted in no clear trend toward an increase in dosimetric error determined by the absolute dose difference, DTA, or gamma index. Varying the delivery machines as well as the beam model (use of a Clinac 6EX 6MV beam model vs. Clinac 21EX 6MV model), also did not show any clear trend towards an increased dosimetric error using the same criteria indicated above.

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.