Prevention and treatment of acute radiation-induced skin reactions : a systematic review and meta-analysis of randomized controlled trials

Background Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling,redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer. Methods We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI). Results Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD −0.92 (95% CI −1.36 to −0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)). Conclusions Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

ortho-Bromo(propa-1,2-dien-1-yl)arenes : substrates for domino reactions

o-Bromo(propa-1,2-dien-1-yl)arenes exhibit novel and orthogonal reactivity under Pd catalysis in the presence of secondary amines to form enamines (concerted Pd insertion, intramolecular carbopalladation, and terminative Buchwald–Hartwig coupling) and of amides to form indoles (addition, Buchwald–Hartwig cyclization, and loss of the acetyl group). The substrates for these reactions can be accessed in a reliable and highly selective two-step process from 2-bromoaryl bromides.

Reactions of simple and peptidic alpha-carboxylate radical anions with dioxygen in the gas phase

alpha-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e. g., fatty acids, peptides and proteins). We have synthesised well-defined alpha-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate ((center dot)CH(2)CO(2)) and 1-carboxylatobutyl (CH(3)CH(2)CH(2)(center dot)CHCO(2)(-)) radical anions with dioxygen yield carbonate (CO(3)(center dot-)) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that C(alpha)-radicals in peptides, formed from free radical damage, combine with dioxygen to form peroxyl radicals that subsequently decompose into imine and keto acid products. Here, we demonstrate that a novel alternative pathway exists for two alpha-carboxylate C(alpha)-radical anions: the acetylglycinate radical anion (CH(3)C(O)NH(center dot)CHCO(2)(-)) and the model peptide radical anion, YGGFG(center dot-). Reaction of these radical anions with dioxygen results in concerted loss of carbon dioxide and hydroxyl radical. The reaction of the acetylglycinate radical anion with dioxygen reveals a two-stage process involving a slow, followed by a fast kinetic regime. Computational modelling suggests the reversible formation of the C(alpha) peroxyl radical facilitates proton transfer from the amide to the carboxylate group, a process reminiscent of, but distinctive from, classical proton-transfer catalysis. Interestingly, inclusion of this isomerization step in the RRKM/ME modelling of a G3SX level potential energy surface enables recapitulation of the experimentally observed two-stage kinetics.

Gas-phase reactions of aryl radicals with 2-butyne : an experimental and theoretical investigation employing the N-methyl-pyridinium-4-yl radical cation

Aromatic radicals form in a variety of reacting gas-phase systems, where their molecular weight growth reactions with unsaturated hydrocarbons are of considerable importance. We have investigated the ion-molecule reaction of the aromatic distonic N-methyl-pyridinium-4-yl (NMP) radical cation with 2-butyne (CH3C CCH3) using ion trap mass spectrometry. Comparison is made to high-level ab initio energy surfaces for the reaction of NMP and for the neutral phenyl radical system. The NMP radical cation reacts rapidly with 2-butyne at ambient temperature, due to the apparent absence of any barrier. The activated vinyl radical adduct predominantly dissociates via loss of a H atom, with lesser amounts of CH3 loss. High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry allows us to identify small quantities of the collisionally deactivated reaction adduct. Statistical reaction rate theory calculations (master equation/RRKM theory) on the NMP + 2-butyne system support our experimental findings, and indicate a mechanism that predominantly involves an allylic resonance-stabilized radical formed via H atom shuttling between the aromatic ring and the C-4 side-chain, followed by cyclization and/or low-energy H atom beta-scission reactions. A similar mechanism is demonstrated for the neutral phenyl radical (Ph center dot)+2-butyne reaction, forming products that include 3-methylindene. The collisionally deactivated reaction adduct is predicted to be quenched in the form of a resonance-stabilized methylphenylallyl radical. Experiments using a 2,5-dichloro substituted methyl-pyridiniumyl radical cation revealed that in this case CH3 loss from the 2-butyne adduct is favoured over H atom loss, verifying the key role of ortho H atoms, and the shuttling mechanism, in the reactions of aromatic radicals with alkynes. As well as being useful phenyl radical analogues, pyridiniumyl radical cations may form in the ionosphere of Titan, where they could undergo rapid molecular weight growth reactions to yield polycyclic aromatic nitrogen hydrocarbons (PANHs).

Ion-molecule reactions reveal facile radical migration in peptides

Ion-molecule reactions between molecular oxygen and peptide radicals in the gas phase demonstrate that radical migration occurs easily within large biomolecules without addition of collisional activation energy.

Unusual cross-ring S(N)2 reactions of M-H (-) ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6.

Anionic migration reactions in aromatic systems effected by collisional activation : Deprotonated anilides containing methoxycarbonyl substituents

Long-range cross-ring reactions are of minor importance in the collision-induced mass spectra (MS/MS) of [M - H]- ions of CH2OCO-C6H4-NHCOR systems: e.g. the loss of 'CD3CO2CH3' from CH3OCO-C6H4-(N) over bar COCD3. Major processes involve (i) losses of radicals to form stable radical anions, e.g. loss of a ring hydrogen atom and losses from the ester (CH3 ., CH3O . and . CO2CH3), (ii) losses of neutral molecules from the amide moiety [e.g. CO (R = H) and CH2CO (R = CH3), and proximity effects when the two substituents are ortho [e.g. loss of (CH3OD+CO2) from o-CH3OCO-C6H4 (N) over bar COCD3].

Unusual cross-ring SN2 reactions of [MH]− ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6.

Self-determination, control, and reactions to changes in workload : a work simulation

The objective of this experimental study is to capture the dynamic temporal processes that occur in changing work settings and to test how work control and individuals' motivational predispositions interact to predict reactions to these changes. To this aim, we examine the moderating effects of global self-determined and non-self-determined motivation, at different levels of work control, on participants' adaptation and stress reactivity to changes in workload during four trials of an inbox activity. Workload was increased or decreased at Trial 3, and adaptation to this change was examined via fluctuations in anxiety, coping, motivation, and performance. In support of the hypotheses, results revealed that, for non-self-determined individuals, low work control was stress-buffering and high work control was stress-exacerbating when predicting anxiety and intrinsic motivation. In contrast, for self-determined individuals, high work control facilitated the adaptive use of planning coping in response to a change in workload. Overall, this pattern of results demonstrates that, while high work control was anxiety-provoking and demotivating for non-self-determined individuals, self-determined individuals used high work control to implement an adaptive antecedent-focused emotion regulation strategy (i.e., planning coping) to meet situational demands. Other interactive effects of global motivation emerged on anxiety, active coping, and task performance. These results and their practical implications are discussed.

General self-efficacy influences affective task reactions during a work simulation : the temporal effects of changes in workload at different levels of control

This study investigated the effects of workload, control, and general self-efficacy on affective task reactions (i.e., demands-ability fit, active coping, and anxiety) during a work simulation. The main goals were: (1) to determine the extent general self-efficacy moderates the effects of demand and control on affective task reactions, and; (2) to determine if this varies as a function of changes in workload. Participants (N=141) completed an inbox activity under conditions of low or high control and within low and high workload conditions. The order of trials varied so that workload increased or decreased. Results revealed individuals with high general self-efficacy reported better demands-abilities fit and active coping as well as less anxiety. Three interactive effects were found. First, it was found that high control increased demands-abilities fit from trial 1 to trial 2, but only when workload decreased. Second, it was found that low efficacious individuals active coping increased in trial 2, but only under high control. Third, it was found that high control helped high efficacious individuals manage anxiety when workload decreased. However, for individuals with low general self-efficacy, neither high nor low control alleviated anxiety (i.e., whether workload increased or decreased over time).

A natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer : a phase III double-blind randomised controlled trial

Purpose To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation induced skin reactions (RISR). Methods and Materials A total of 174 patients were randomised and participated in the study. Patients either received Cream 1 (the natural oil-based emulsion containing allantoin) or Cream 2 (aqueous cream). Skin toxicity, pain, itching and skin-related quality of life scores were collected for up to four weeks after radiation treatment. Results Patients who received Cream 1 had a significantly lower average level of Common Toxicity Criteria at week 3 (p<0.05), but had statistically higher average levels of skin toxicity at weeks 7, 8 and 9 (all p<0.001). Similar results were observed when skin toxicity was analysed by grades. With regards to pain, patients in the Cream 2 group had a significantly higher average level of worst pain (p<0.05) and itching (p=0.046) compared to the Cream 1 group at week 3, however these differences were not observed at other weeks. In addition, there was a strong trend for Cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison to Cream 1 (p=0.056). Overall, more participants in the Cream 1 group were required to use another topical treatment at weeks 8 (p=0.049) and 9 (p=0.01). Conclusion The natural oil-based emulsion containing allantoin appears to have similar effects for managing skin toxicity compared to aqueous cream up to week 5, however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream appears to be a more preferred option.

Measuring Competence in Supervisees and Supervisors : Satisfaction and Related Reactions in Supervision

Supervision is a highly valued component of practitioner training. This chapter discusses the following: factors influencing perceived satisfaction and alliance; and how satisfaction, alliance, and supervision relationships are currently measured; and reviews issues with the concept and its assessment. Given the importance of the supervisory relationship and of the supervisory alliance for the effectiveness of supervision and for the welfare of supervisees, the routine, repeated measurement of both these concepts, together with supervisee satisfaction, also assumes considerable utility. The chapter describes a selection of some commonly used measures: Supervisee Satisfaction Questionnaire (SSQ), Supervisory Relationship Questionnaire (SRQ), Supervisory Relationship Measure (SRM), Supervision Attitude Scale (SAS), Supervisory Working Alliance Inventory (SWAI), Supervisory Styles Inventory (SSI), Role Conflict and Ambiguity Inventory (RCAIC), and Evaluation Process within Supervision Inventory (EPSI).

Dynamic input to determine hip joint moments, power and work on the prosthetic limb of transfemoral amputees: ground reactions vs knee reactions

Study Design: Comparative analysis Background: Calculations of lower limbs kinetics are limited by floor-mounted force-plates. Objectives: Comparison of hip joint moments, power and mechanical work on the prosthetic limb of a transfemoral amputee calculated by inverse dynamics using either the ground reactions (force-plates) or knee reactions (transducer). Methods: Kinematics, ground reactions and knee reactions were collected using a motion analysis system, two force-plates and a multi-axial transducer mounted below the socket, respectively. Results: The inverse dynamics using ground reactions under-estimated the peaks of hip energy generation and absorption occurring at 63 % and 76 % of the gait cycle (GC) by 28 % and 54 %, respectively. This method over-estimated a phase of negative work at the hip (from 37 %GC to 56 %GC) by 24%. It under-estimated the phases of positive (from 57 %GC to 72 %GC) and negative (from 73 %GC to 98 %GC) work at the hip by 11 % and 58%, respectively. Conclusions: A transducer mounted within the prosthesis has the capacity to provide more realistic kinetics of the prosthetic limb because it enables assessment of multiple consecutive steps and a wide range of activities without issues of foot placement on force-plates. CLINICAL RELEVANCE The hip is the only joint that an amputee controls directly to set in motion the prosthesis. Hip joint kinetics are associated with joint degeneration, low back pain, risks of fall, etc. Therefore, realistic assessment of hip kinetics over multiple gait cycles and a wide range of activities is essential.