A systematic overview of radiation therapy effects in head and neck cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for head and neck cancer is based on data from 39 randomized trials and 1 meta-analysis. In total, 40 scientific articles are included, involving 20893 patients. The results were compared with those of a similar overview from 1996 including 79 174 patients. The conclusions reached can be summarized as follows: General, non-nasopharynx. Substantial evidence indicates that the tumour effect of radiotherapy can be increased by the concomitant administration of chemotherapeutic agents, particularly cisplatin and 5-fluorouracil. There is moderate evidence of a survival benefit of radiation combined with concomitant chemotherapy compared to radiation alone. However, the results are equivocal. There is substantial evidence in published studies for an increased frequency of severe acute side effects as a result of concomitant chemotherapy and radiotherapy. There are very few studies that allow any estimates of the risk for serious late side effects. There is a weak indication of an increased risk for serious fibrosis. Comment: The general quality of studies and the lack of information on serious side effects indicate a need for large, well-designed clinical studies with a reasonable follow-up. Larynx preservation studies. There is strong evidence that larynx preservation is possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers when treated with neoadjuvant chemotherapy and radical radiotherapy There is a non-significant trend for the overall survival being lower in non-surgically treated patients than in those treated with primary surgery and postoperative radiotherapy Nasopharynx. There is moderate evidence that patients with nasopharyngeal carcinomas of the endemic type benefit from therapy with a combination of chemotherapy and radical radiotherapy. However, the results from the reported studies are equivocal. There is some indication that the acute side effects of radiation are more severe in the concomitant setting than in the neoadjuvant. Comment: There are no data on serious late toxicity. Dose, fractionation schedules. There is some evidence that certain schedules of altered fractionation improve tumour control without increasing severe late side effects. There is some evidence that nervous tissues are more susceptible to damage by altered fractionation. Solid data shows that altered fractionation increases acute side effects. There is moderate evidence that accelerated hyperfractionation may reduce the frequency of serious late side effects while retaining a similar tumour effect as conventional radiotherapy Hypoxic cell sensitizers. Most reported trials reject the usefulness of nitroimidazole derivatives for sensitization of hypoxic tumour cells. There is some evidence that patients with tumours in the pharynx and larynx may benefit from sensitization by nimorazole. Prophylactic treatment of side effects. There is weak evidence that local antibiotics have a clinically significant effect in preventing acute radiotherapy side effects. There is insufficient evidence that radioprotective agents offer clinically significant protection of parotid glands (one study in two publications). There is insufficient evidence that radioprotective agents do not spare tumour tissue. Since the previous report no randomized studies comparing the effectiveness of external beam radiotherapy and brachytherapy have been performed. Both methods are well established and have independently proved to be effective in the treatment of certain head and neck cancers. No conclusion can be drawn regarding their relative effectiveness. Since the previous report no data to guide the use of intraoperative radiotherapy have been identified.     

Contingency Learning Deficits and Generalization in Chronic Unilateral Hand Pain Patients

Contingency learning, in particular the formation of danger beliefs, underpins conditioned fear and avoidance behavior, yet equally important is the formation of safety beliefs. That is, when threat beliefs and accompanying fear/avoidance spread to technically safe cues, it might cause disability. Indeed, such overgeneralization has been advanced as a transdiagnostic pathologic marker, but it has not been investigated in chronic pain. Using a novel hand pain scenario contingency learning task, we tested the hypotheses that chronic hand pain patients demonstrate less differential pain expectancy judgments because of poor safety learning and demonstrate broader generalization gradients than healthy controls. Participants viewed digitized 3-dimensional hands in different postures presented in random order (conditioned stimulus [CS]) and rated the likelihood that a fictive patient would feel pain when moving the hand into that posture. Subsequently, the outcome (pain/no pain) was presented on the screen. One hand posture was followed by pain (CS+), another was not (CS−). Generalization was tested using novel hand postures (generalization stimuli) that varied in how similar they were to the original conditioned stimuli. Patients, but not healthy controls, demonstrated a contingency learning deficit determined by impaired safety learning, but not by exaggerated pain expectancy toward the CS+. Patients showed flatter, asymmetric generalization gradients than the healthy controls did, with higher pain expectancy for novel postures that were more similar to the original CS−. The results clearly uphold our hypotheses and suggest that contingency learning deficits might be important in the development and maintenance of the chronic pain–related disability.     

Burden of type 2 diabetes attributed to lower educational levels in Sweden

Background

Verbal autopsy (VA) has often been used for point estimates of cause-specific mortality, but seldom to characterize long-term changes in epidemic patterns. Monitoring emerging causes of death involves practitioners' developing perceptions of diseases and demands consistent methods and practices. Here we retrospectively analyze HIV-related mortality in South Africa, using physician and modeled interpretation.

Methods

Between 1992 and 2005, 94% of 6,153 deaths which occurred in the Agincourt subdistrict had VAs completed, and coded by two physicians and the InterVA model. The physician causes of death were consolidated into a single consensus underlying cause per case, with an additional physician arbitrating where different diagnoses persisted. HIV-related mortality rates and proportions of deaths coded as HIV-related by individual physicians, physician consensus, and the InterVA model were compared over time.

Results

Approximately 20% of deaths were HIV-related, ranging from early low levels to tenfold-higher later population rates (2.5 per 1,000 person-years). Rates were higher among children under 5 years and adults 20 to 64 years. Adult mortality shifted to older ages as the epidemic progressed, with a noticeable number of HIV-related deaths in the over-65 year age group latterly. Early InterVA results suggested slightly higher initial HIV-related mortality than physician consensus found. Overall, physician consensus and InterVA results characterized the epidemic very similarly. Individual physicians showed marked interobserver variation, with consensus findings generally reflecting slightly lower proportions of HIV-related deaths. Aggregated findings for first versus second physician did not differ appreciably.

Conclusions

VA effectively detected a very significant epidemic of HIV-related mortality. Using either physicians or InterVA gave closely comparable findings regarding the epidemic. The consistency between two physician coders per case (from a pool of 14) suggests that double coding may be unnecessary, although the consensus rate of HIV-related mortality was approximately 8% lower than by individual physicians. Consistency within and between individual physicians, individual perceptions of epidemic dynamics, and the inherent consistency of models are important considerations here. The ability of the InterVA model to track a more than tenfold increase in HIV-related mortality over time suggests that finely tuned "local" versions of models for VA interpretation are not necessary.     

Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans

After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term.     

EuroSCORE predicts intensive care unit stay and costs of open heart surgery

Background

This study aimed to determine whether the preoperative risk stratification model EuroSCORE predicts the different components of resource utilization in open heart surgery.

Methods

Data for all adult patients undergoing heart surgery at the University Hospital of Lund, Sweden, between 1999 and 2002 were prospectively collected. Costs were calculated for the surgery and intensive care and ward stay for each patient (excluding transplant cases and patients who died intraoperatively). Regression analysis was applied to evaluate the correlation between EuroSCORE and costs. The predictive accuracy for prolonged postoperative intensive care unit (ICU) stay was assessed by the Hosmer-Lemeshow goodness-of-fit test. The discriminatory power was evaluated by calculating the areas under receiver operating characteristics curves.

Results

The study included 3,404 patients. The mean cost for the surgery was $7,300, in the ICU $3,746, and in the ward $3,500. Total cost was significantly correlated with EuroSCORE, with a correlation coefficient of 0.47 (p < 0.0001); the correlation coefficient was 0.31 for the surgery cost, 0.46 for the ICU cost, and 0.11 for the ward cost. The Hosmer-Lemeshow p value for EuroSCORE prediction of more than 2 days' stay in the ICU was 0.40, indicating good accuracy. The area under the receiver operating characteristics curve was 0.78. The probability of an ICU stay exceeding 2 days was more than 50% at a EuroSCORE of 14 or more.

Conclusions

In this single-institution study, the additive EuroSCORE algorithm could be used to predict ICU cost and also an ICU stay of more than 2 days after open heart surgery.     

The validity of a separate classification of cryptogenic localization related epilepsy amongst childhood epilepsies.

INTRODUCTION: One-third of children with epilepsy are classified as having a cryptogenic localization related epilepsy (CLRE). In cohort studies CLRE is often grouped together with either symptomatic localization related epilepsy (SLRE) or idiopathic generalized epilepsy (IGE). Therefore, this categorization is not specific enough and will not lead to prognostic or treatment information. We objectified the classification differences between these categories. METHODS: A total of 114 children admitted to our epilepsy centre underwent a standardized clinical analysis, which yielded age at onset, duration of the epilepsy, seizure frequency, seizure type, percentage of interictal epileptiform activity on EEG (IEA), type of treatment, and full scale IQ. These variables are regarded the characteristics of the epilepsy, and used in a discriminant function analysis. RESULTS: IEA was found to be the only variable to distinguish between groups of epilepsy. SLRE could easily be distinguished significantly from IGE and CLRE, while the latter two did not differ significantly. Discriminant function analysis combined the variables into two functions, applicable to classify the children. By applying this statistical analysis method, the groups clinically classified as SLRE and IGE were mostly classified as SLRE (71.4%) and IGE (57.9%). However, CLRE appeared difficult to classify (49.2%), and most children were classified as either SLRE (19%) or IGE (31.7%). CONCLUSION: The current opinion that CLRE is 'probably symptomatic' cannot be confirmed in all cases in this study. It is most likely that the current CLRE population consists of both children with eventually SLRE, as well as yet to be described syndromes to be classified as idiopathic epilepsies. We emphasize the need for separate studies regarding children with 'probably symptomatic' (cryptogenic) localization related epilepsy, as this will maximally help children, caretakers and treating physicians to achieve the best possible outcome.     

Cyclin D1 amplification in chromosomal band 11q13 is associated with overrepresentation of 3q21-q29 in head and neck carcinomas

Eight cytogenetically characterized head and neck squamous cell carcinomas (HNSCCs) with CCND1 amplification in the form of a homogeneously staining region (hsr) in 11q13 were studied by COBRA FISH and FISH with specific probes to identify and characterize chromosomal segments added to the derivative chromosomes 11. In 4 of the tumors, it could be recognized that the material added was derived from the long arm of chromosome 3. The rearrangements were interpreted as der(11)hsr(11)(q13)t(3;11)(q21;q13) in 3 cases and as der(11)hsr(11)(q13)t(3;11)(q14;q13) in 1 case. In the other 4 cases, material from chromosomes 1, 16, or 19 was added to the derivative chromosomes 11. By further FISH analysis with 14 YAC clones spanning 3q13-q21 in the 4 tumors with der(11)hsr(11)t(3;11), it could be shown that they had different breakpoints at the molecular level, excluding the possibility that a particular gene was rearranged by the translocations. More surprisingly, gain of the 3q21-q29 segment was found in all 8 tumors with hsr in 11q13 and loss of 3p was seen in 7 of the tumors. These findings strongly indicate a synergistic effect of CCND1 amplification, loss of distal 11q, 3q gain and 3p deletion in HNSCC development and also suggests a mechanistic link between intrachromosomal amplification at 11q13 and recombination with distal 3q.     

End‐of‐life decision‐making in Belgium,Denmark, Sweden and Switzerland: does place of death make a difference?

OBJECTIVE: To examine differences in end-of-life decision-making in patients dying at home, in a hospital or in a care home. DESIGN: A death certificate study: certifying physicians from representative samples of death certificates, taken between June 2001 and February 2002, were sent questionnaires on the end-of-life decision-making preceding the patient's death. SETTING: Four European countries: Belgium (Flanders), Denmark, Sweden, and Switzerland (German-speaking part). MAIN OUTCOME MEASURES: The incidence of and communication in different end-of-life decisions: physician-assisted death, alleviation of pain/symptoms with a possible life-shortening effect, and non-treatment decisions. RESULTS: Response rates ranged from 59% in Belgium to 69% in Switzerland. The total number of deaths studied was 12 492. Among all non-sudden deaths the incidence of several end-of-life decisions varied by place of death. Physician-assisted death occurred relatively more often at home (0.3-5.1%); non-treatment decisions generally occurred more often in hospitals (22.4-41.3%), although they were also frequently taken in care homes in Belgium (26.0%) and Switzerland (43.1%). Continuous deep sedation, in particular without the administration of food and fluids, was more likely to occur in hospitals. At home, end-of-life decisions were usually more often discussed with patients. The incidence of discussion with other caregivers was generally relatively low at home compared with in hospitals or care homes. CONCLUSION: The results suggest the possibility that end-of-life decision-making is related to the care setting where people die. The study results seem to call for the development of good end-of-life care options and end-of-life communication guidelines in all settings.     

Anchorage provided during intra-arch distal molar movement: a comparison between the Nance appliance and a fixed frontal bite plane

The aim of this retrospective study was to evaluate and compare the anchorage provided with the Nance appliance (NA) and the fixed frontal bite plane (FBP) during intra-arch distal molar movement. After a sample size calculation, 20 patients were recruited and randomly selected for each group from patients who fulfilled the following criteria: use of an intra-arch Ni-Ti coil appliance with either NA or FBP to provide anchorage during a six-month molar distalization period, no orthodontic treatment before molar distalization, and first and second maxillary molars in occlusion. The outcome measures assessed were anchorage loss, ie, anterior movement of maxillary central incisors, distal movement of maxillary molars, and bite opening effect. The mean age in the NA group was 14.7 years (SD 1.09) and in the FBP group 15.0 years (SD 0.99). The data revealed that the maxillary central incisors moved anteriorly 1.4 mm in the NA group and 1.9 mm in the FBP group. The difference in anchorage loss was not significant. The mean amount of molar distalization within the maxilla was 1.7 mm in the NA group and 1.8 mm in the FBP group. In both groups, the overbite was significantly reduced and the overbite was decreased significantly more in the FBP group. Because neither the NA nor FBP provided stable anchorage, a second treatment phase is recommended to reverse the anchorage loss after distal molar movement. If molar distalization is planned in deep bite cases, the FBP is the anchorage system of choice.