[Impact of adapted physical activity on joint pain induced under adjuvant hormone therapy for breast cancer: A review of the literature]. / Impact de l'activité physique adaptée sur les douleurs articulaires induites sous hormonothérapie adjuvante du cancer du sein : une revue de la littérature.

Hormone therapy provides an excellent survival rate after cancer but has many side effects, including joint pain in one out of two women. This leads about 13 % of women to stop their treatment within the first 6 months, impacting on its effectiveness, survival and the risk of recurrence. In order to better manage pain and quality of life, physical activity is highly recommended. In this context, the present review proposes a state of the art on the effects of adapted physical activity, based on the works referenced in PubMed. These studies show that physical activity has proved its worth in the primary prevention of cancer and is being evaluated in secondary prevention, particularly in the reduction of adverse effects. Overall, there is a reduction in joint pain, an improvement in quality of life and fatigue. Physical activity also plays a role in tertiary prevention. Paradoxically, oncologists and educators often note a reduction in the practice of physical activity due to fear of the onset of pain. It seems necessary to reinforce communication with patients and health professionals and to recommend the practice of physical activity in an appropriate setting.

Meditation involving people with cancer, medical staff and witnesses: a pilot study exploring improvement in wellness and connectedness.

INTRODUCTION: Mindfulness meditation is likely to promote better management of stress, pain and negative emotions. We propose to address the benefit of meditation in an open setting associating people with cancer (target population), medical staff and witnesses (neither patient nor medical staff). This study aims (1) to evaluate the effects of meditation on wellness improvement and (2) to identify criteria and modalities for a subsequent randomised study. METHODS AND ANALYSIS: We propose a longitudinal pilot study consisting of a non-randomised experimental preintervention/postintervention survey. The intervention consists in delivering a meditation programme (12 weekly meditation sessions of 1.5 hours each), specifically adapted to our target population and addressing our research hypothesis in an open setting involving people with cancer, medical staff and witnesses (equally distributed in two groups of 15 participants). The main objective is to evaluate participants' adherence to the programme. The effects of meditation will be evaluated on stress, quality of life, feeling of personal effectiveness, on the development of mindfulness and empathy, and on satisfaction and perception of a change in quality of life. We will also measure the putative added value of 'meditating together'. This study is expected to allow validating the evaluation tools and refining the modalities of the workshops. We expect to demonstrate the evolution that this meditation-based intervention induces in the participants. We aim to promote bridge-building, between patients, medical staff but also others. In this way, one's own suffering may be understood in the light of others' suffering, thereby promoting the sense of otherness and giving insights into 'living better with'. This exploratory study will investigate the relevance of this hypothesis, which could then be explored by a randomised study. ETHICS AND DISSEMINATION: The protocol was approved by the local ethics committee (Comité de Protection des Personnes Est II). Trial findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04410185.

[Optimization of the "pharmaceutical consultation" practiced by pharmacists - Review, feedback and future proposals for development since the introduction of the initiative in 2013 focusing on the Calvados area]. / Optimisation des entretiens pharmaceutiques à l'officine ­ Bilan et retour de cette mission mise en place en 2013 et perspectives de développement dans le département du Calvados.

In 2012, a National Agreement of Pharmacists was initiated in France and then amended in 2013 to introduce the "Pharmaceutical consultation". These consultations must be conducted by the pharmacist with the patient in a confidential area in pharmacy or patient residence. The objective is to decrease the frequency of negative side effects of the medical treatments (anti-vitamins k, direct oral anticoagulants and inhaled corticoid) and to improve the correct use of medication therefore assure the safety of the patient. This initiative also recognizes the expertise of the pharmacists who are remunerated with 50 euros per year and per patient from Social Security. This publication is based on a survey conducted in the whole Calvados area and it is based on several individual interviews. It gives a clear picture about how effective the practice has been so far. It shows that the "Pharmaceutical consultation" is currently only proposed to patients by 40% of pharmacists in this area, additionally the practice decreased by 85% in the pharmacies since 2013. However, 8 on 10 pharmacists recognized a real benefit for patients who subscribed for consultation. Independently, the number of non-subsidized conversation initiatives carried out by pharmacists (anti-tobacco, pregnancy, diabetes) are increasing. This finding leads to the investigation of the causes for not practicing the "Pharmaceutical consultation". The causes for not carrying out the consultations were identified, quantified, analysed and classified with a view to proposing short, medium and long time actions to optimize the "Pharmaceutical consultation" in a financially feasible manner. Nine practical proposals were identified and groups in three areas of improvement: communication, remuneration and organization.

Evaluation of patients' needs to design and assess a patient education program in cancer pain.

Purpose: Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation. Patients and methods: Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE. Results: Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in <30% of patients. Almost all patients (97.1%) stated pain education as beneficial, with a preference for individualized sessions (41.2%). In addition, the assessment criteria for its future evaluation were refined. Conclusion: Targeted population mainly concerned patients with persistent pain. Only half of patients reported pain relief despite antalgics. Patient education was declared as beneficial for almost all participants. Practice implications: Tailoring a pain TPE on patients' needs has the potential to help them to optimally manage their pain daily.

[Nutritional counseling in community pharmacies within the framework of the French National Nutrition and Health Program]. / Conseils nutritionnels à l'officine dans le cadre du Programme National Nutrition Santé

INTRODUCTION: The French National Nutrition and Health Program (PNNS), nutrition policy whose objective is to improve the health status of the population, establishes dietary guidelines to answer priority nutritional objectives. The pharmacist, as the drug specialist, dispenses not only products but also services adapted to their patients' needs such as nutritional counseling in order to improve their quality of life. The purpose of this work was to develop nutritional tip sheets answering to the PNNS recommendations that could be exploited by pharmacists to advise their patients. MATERIALS AND METHOD: Two types of tools were developed: self-test on nutrition, aiming at arousing the dialogue between patient and pharmacist on nutrition, and nutritional tip sheets raising the main advices to be dispensed according to the patients' profiles, with their scientific argumentation. RESULTS: The implementation of this tool was tested in a pilot pharmacy, where the utility of nutritional tip sheets was assessed in 24 patients. Among the patients who answered (46 %, that is 11 respondents), 82 % (9 patients) considered that these tip sheets were useful to improve their lifestyle. Nutritional tip sheets answering the priority objectives of the PNNS and relatives to the main diseases were most frequently used. DISCUSSION: It would be sensible to widen this nutritional tool to other pharmacies, especially for the most popular sheets. The implementation of a file listing these nutritional tip sheets could constitute an in-service training tool. CONCLUSION: This nutritional device could contribute to therapeutic education provided by community pharmacists.

Assessment of nutritional status and quality of life in patients treated for head and neck cancer.

The purpose of this study was to identify tools for the assessment of nutritional status in head and neck cancer patients, to evaluate the impact of malnutrition on therapeutic management and quality of life and to propose a simple screening approach adapted to routine clinical practice. The authors conducted a review of the literature to identify tools for the assessment of nutritional status in head and neck cancer patients published in French and English. Articles were obtained from the PubMed database and from the references of these articles and selected journals, using the keywords: "nutritional assessment", and "head and neck" and "cancer". Anthropometric indices, laboratory parameters, dietary intake assessment, clinical scores and nutritional risk scores used in patients with head and neck cancers are presented. The relevance of these tools in clinical practice and in research is discussed, together with the links between nutritional status and quality of life. This article is designed to help teams involved in the management of patients with head and neck cancer to choose the most appropriate tools for assessment of nutritional status according to their resources and their objectives.

Quality of life tools in head and neck oncology.

OBJECTIVE: Quality of life (QoL) is now as much an assessment criterion in clinical trials in head and neck oncology as are survival and response rate. It is therefore important to be able to choose an adapted tool from the wide range of QoL instruments available. The present study presents an inventory of QoL scales validated in their French-language version, to facilitate the selection of appropriate tools showing good psychometric properties. MATERIALS AND METHODS: QoL scales cited in all 492 French and English language articles published between March 1st, 2006 and April 3rd, 2012, referenced on Medline and retrieved using the keywords "quality of life" AND "head and neck" AND "cancer", were inventoried and classified thematically in a search of the literature. RESULTS: Ninety QoL scales are presented by theme (ORL oncology, voice, swallowing and mastication, mucosities and xerostomia, etc.), specifying psychometric quality and citation level. CONCLUSION: The present report constitutes a guide to selecting QoL tools adapted to head and neck oncology studies.

Effects of alcohol consumption on biomarkers of oxidative damage to DNA and lipids in ethanol-fed pigs.

Chronic alcohol consumption is known to result in tissue injury, particularly in the liver, and is considered a major risk factor for cancers of the upper respiratory tract. Here we assessed the oxidative effects of subchronic ethanol consumption on DNA and lipids by measuring biomarkers 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and malondialdehyde (MDA), respectively. Physiological responses of pigs (n = 4) administered ethanol in drinking water for 39 days were compared with those of water-fed pigs (n = 4). Alcoholisation resulted in serum ethanol concentration of 1.90 g L(-1) and in a moderate but significant increase in alanine aminotransferase activity, an index of liver injury. However, between the alcoholised and control groups there were no significant differences in the levels of 8-oxodG (8-oxodG per 10(6) 2'deoxyguanosine) from leucocytes (2.52 ± 0.42 Vs 2.39 ± 0.34) or from target organs, liver, cardia and oesophagus. Serum MDA levels were also similar in ethanol-fed pigs (0.33 ± 0.04 µM) and controls (0.28 ± 0.03 µM). Interestingly, levels of 8-oxodG in cardia were positively correlated with those in oesophagus (Spearman correlation coefficient R = 1, P < 0.0001). Our results suggest that alcohol consumption may not cause oxidative damage to DNA and lipids as measured by 8-oxodG and MDA, respectively. The duration of alcoholisation and the potential alcohol-induced nutritional deficiency may be critical determinants of ethanol toxicity. Relevant biomarkers, such as factors involved in sensitization to ethanol-induced oxidative stress are required to better elucidate the relationship between alcohol consumption, oxidative stress and carcinogenesis.

Nutritional support and quality of life in cancer patients undergoing palliative care.

In palliative care, the nutrition provided has to be tailored to the patient's needs, enhancing patient comfort and quality of life (QoL). We conducted a literature search to review methods of measuring QoL, and modalities of nutritional intervention and their influence on QoL of cancer patients in palliative care. Original papers published in English were selected from PubMed database by using the search terms, palliative medicine, cancer, nutrition and quality of life. Specific tools that are particularly recommended to assess QoL in a palliative care setting are reviewed. The main goal in palliative care is to maintain oral nutrition by providing nutritional counselling. Enteral nutritional support showed inconsistent effects on survival and QoL. An evidence-base for parenteral nutrition is still lacking. Ethical considerations concerning provision of food and hydration in end-of-life care are discussed. Nutritional status should be assessed early and regularly during treatment using appropriate tools. In the particularly acute context of palliative care, optimal patient management requires adequate education and counselling to patients and families. Meaningful interactions between the patient, caregivers and medical team would also increase the chance of resolving nutrition-related issues and help to fulfil each patient's specific nutritional needs and thus improve the QoL.

Cigarette smoking and urinary 3-alkyladenine excretion in man.

A recently developed technique to measure several 3-alkyladenines (3-alkAde) simultaneously in urine has been applied to study alkylating agent exposure arising from cigarette smoke. A volunteer who was a moderate smoker (10-32 cigarettes per day) excreted significantly more 3-methyladenine (3-MeAde) on days when he smoked than when he did not smoke. In contrast, there was no significant difference in 3-MeAde excretion in a light smoker (less than 17 cigarettes per day) on smoking compared to nonsmoking days. However, in volunteers who consumed a standardized diet low in preformed 3-MeAde, there was a smoking-related increase in 3-MeAde excretion even at low levels of cigarette use (less than 11 cigarettes per day). In the same volunteers, no evidence of smoking-related excretion of 3-(2-hydroxyethyl)adenine could be seen. In contrast, levels of urinary 3-ethyladenine (3-EtAde) increased slightly in smokers on standardized diets. Furthermore, since the normal background level of 3-EtAde was low, an exposure-dependent increase in this adduct was seen in two smokers on freechoice diets over a 15 day period. The agent(s) responsible for the increase in 3-EtAde excretion have not been identified, but preliminary results suggest that a direct-acting ethylating compound is present in tobacco smoke.

DNA base adducts in urine andwhite blood cells of cancer patients receiving combination chemotherapies which include N-methyl-N-nitrosourea.

Abstract Urinary 3-methyladenine (3-MeAde) excretion andlymphocyte DNA adduct formation was studied in 15 patients receiving methylnitrosourea (MNU) at several dose levels (250 mg, 300 mg and600 mg total dose, 143-385 mg m(-2)) as part of various combination chemotherapies for advanced tumours (malignant melanoma, lymphoblastic lymphosarcorna andHodgkin's disease). Urinary 3-MeAde levels were significantly increased over background in patients at all dose levels (p < 0.001) andthe increases were dose-dependent (r = 0.77, p < 0.01). There were large interindividual variations in the excretion of 3-MeAde at each dose of MNU. In a subset of patients, N7-methyl-2-deoxyguanosine (7-MedG) andO(6)-methyl-2'-deoxyguanosine (O(6)-WedG) levels in DNA from blood leucocytes showed dose-dependent increases, however there were no simple relationships between urinary methylated DNA bases andleucocyte DNA adducts. Levels of adducts in leucocyte DNA (7-MedG, < 17-217 µmol mol(-1) dG; O(6)-WedG, < 1.6-35 µmol mol(-1) dG) were comparable with those reported for other methylating chemotherapeutic drugs. Leucocyte DNA andurinary methyl adducts may be useful markers of individual responses to treatment with methylating drugs.

Noninvasive methods for measuring DNA alkylation in experimental animals and humans.

Alkylpurines are liberated from alkylated DNA by glycosylase repair enzymes and, in most cases, excreted in urine without further metabolism. This phenomenon forms the basis of noninvasive methods to measure DNA alkylation in vivo. In the case of methyl adducts, such as 7-methylguanine (7-MeGua), natural backgrounds exist due to RNA turnover. However, deuterated (d3) methylating agents or precursors give rise to d3-7-MeGua and d3-3-methyladenine (3-MeAde), which can be readily quantitated using gas chromatography-mass spectrometry (GC-MS). A deuterated probe drug, such as d6-aminopyrine, can be used to measure endogenous nitrosation levels in experimental animals. In contrast, for higher alkyl homologues of alkylpurines, natural backgrounds are low or nonexistent and can be directly measured by GC-MS using stable isotope labeled internal standards. For example, increased levels of urinary 3-ethyladenine were observed in cigarette smokers. Due to recent advances in analytical methodology, notably immunoaffinity cleanup of urine, measurements of excreted DNA adducts can be used in studies in human populations exposed to low levels of alkylating carcinogens.

Urinary markers for measuring exposure to endogenous and exogenous alkylating agents and precursors.

Noninvasive methodologies for measuring carcinogen exposure in humans, based on the use of urinary markers, are being developed and validated for use in molecular epidemiological studies. A range of 3-alkyladenines can be determined in urine samples by an immunoaffinity purification-GC/MS approach [3-methyladenine, 3-ethyladenine, 3-(2-hydroxyethyl)adenine, and 3-benzyladenine]. Using this method, recent results in human subjects suggest that urinary 3-alkyladenines are potentially useful markers of alkylating agent exposure, particularly where the backgrounds of such adducts are much lower than 3-methyladenine. Urinary excretion of S-benzylmercapturic acid has been studied in experimental animals as a marker of exposure to benzylating agents such as N-nitroso-methylbenzylamine. 3-Nitrotyrosine (NTyr) is formed in vivo in tissue or blood proteins after exposure to nitrosating and/or nitrating agents such as tetranitromethane. After turnover of proteins, NTyr is released and excreted in urine as metabolites 3-nitro-4-hydroxy-phenylacetic acid and 3-nitro-4-hydroxyphenylacetic acid, which are determined by GC with a thermal energy analyzer. The sensitivity and specificity, combined with ease of use, of these noninvasive biomonitoring approaches means that they may be readily incorporated into molecular epidemiological studies in which exposure to nitrosating and alkylating agents may be important risk factors.

Immunoaffinity purification and gas chromatography-mass spectrometric quantification of 3-alkyladenines in urine: metabolism studies and basal excretion levels in man.

Immunoaffinity gels were prepared by coupling monoclonal antibody (Mab) EM-6-47 to protein A-Sepharose, and were used to make small columns retaining 3-alkyladenines (3-alkAde) of diverse structure. An analytical procedure for determination of 3-methyladenine (3-MeAde), 3-ethyladenine (3-EtAde), 3-(2-hydroxyethyl)adenine (3-HOEtAde) and 3-benzyladenine (3-BzAde) was developed. Deuterated internal standards (d3-3-MeAde, d5-3-EtAde, d4-3-HOEtAde and d7-3-BzAde) were synthesized and added to urine samples prior to immunoaffinity purification. 3-alkAde were separated and quantitated as tert-butyl-dimethylsilyl (TBDMS) derivatives by capillary gas chromatography-low resolution mass spectrometry (GC-MS). Detection limits for 3-MeAde, 3-EtAde and 3-HOEtAde were 0.2 pmol/ml urine and for 3-BzAde, 1 pmol/ml urine. Studies in two volunteers showed that 3-MeAde and 3-HOEtAde were excreted almost quantitatively (> 90%) within 24 h, that 3-EtAde was less well excreted (67-74%) and that 3-BzAde was poorly excreted (21-25%). Studies on basal levels of 3-alkAde urinary excretion in three volunteers showed that 3-MeAde was > 90% derived from the diet as the preformed product. 3-HOEtAde was present at approximately 10 nmol/day and was reduced to approximately 1 nmol/day when the diet was standardized suggesting that it is also dietary in origin. 3-BzAde was not detected in human urine. 3-EtAde was not only excreted at low levels (< 1 nmol/day) but was also only very slightly affected by diet. This general and sensitive method will be useful in biomonitoring studies in subjects exposed to alkylating agents of diverse structure.

Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice.

The formation of 7-(2-hydroxyethyl)guanine (7-HEG) in DNA of target and nontarget tissues was investigated in male B6C3F1 mice (20/group) and F344 rats (10/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) and mice exposed to 100 ppm ETO for 1 or 3 days or 1, 2, or 4 weeks (5 days/week). The persistence of 7-HEG was studied in mice killed up to 7 days after cessation of the 4-week time-course study. In addition, the formation of O6-(2-hydroxyethyl)guanine and 3-(2-hydroxyethyl)adenine was evaluated in rats exposed to 300 ppm ETO. DNA samples from control and treated animals were analyzed for 7-HEG using neutral thermal hydrolysis, microconcentration, and high-performance liquid chromatography separation with fluorescence detection. Fluorescence-linked high-performance liquid chromatography was used for O6-(2-hydroxyethyl)guanine quantitation, and immunochromatography and gas chromatography-mass spectrometry were used for 3-(2-hydroxyethyl)adenine detection. Analysis of DNA from tissues of control mice and rats revealed the presence of peaks equivalent to 2-6 pmol 7-HEG/mg DNA. In mice exposed to 100 ppm ETO, 7-HEG accumulated to a similar extent in target and nontarget tissues, with adduct concentrations ranging from 17.5 +/- 3.0 (SE) (testis) to 32.9 +/- 1.9 (lung) pmol adduct/mg DNA after 4 weeks of exposure. Concurrent exposures of mice and rats to 100 ppm ETO for 4 weeks led to 2- to 3-fold lower concentrations of 7-HEG in mouse DNA in all tissues compared to rat DNA. 7-HEG disappeared slowly in a nearly linear fashion from the DNA of mouse kidney (t1/2 = 6.9 days) and rat brain and lung (t1/2 = 5.4-5.8 days), which was consistent with the loss of adduct mainly by chemical depurination. In contrast, a more rapid removal of 7-HEG from other mouse (t1/2 = 1.0-2.3 days) and rat (t1/2 = 2.9-4.8 days) tissues was consistent with adduct loss by depurination and DNA repair. Dose-response relationships for 7-HEG were nonlinear in both mice and rats, with the alkylating efficiency of ETO increasing at high exposures.(ABSTRACT TRUNCATED AT 400 WORDS)

A rapid gas chromatography-mass spectrometry method for the determination of urinary 3-methyladenine: application in human subjects.

A rapid gas chromatography-mass spectrometry method, employing immunoaffinity clean-up, has been developed for the measurement of 3-methyladenine in human urine samples. A wide variation in levels of urinary 3-methyladenine was observed, indicating that at least some may be derived from the diet and not be related to endogenous nitrosation and subsequent methylation.

Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry.

An ammonium sulfate precipitated immunoglobin G (IgG) fraction from rabbit antiserum, prepared by use of novel haptenic derivatives, was used to make immunoaffinity columns for purification of 3-methyladenine (3-MeAde) from human urine. IgG was covalently bound to protein A-Sepharose, and the resulting affinity gel columns were sufficiently stable for multiple reuse. 3-MeAde (up to 200 ng) was adsorbed at pH 7.4 and, after extensive washing, eluted with 1 M acetic acid. Recovery of 3-MeAde was typically greater than 90%. For gas chromatography-mass spectrometry analysis, deuterium-labeled (d3) 3-MeAde (50 ng per sample) was used as an internal standard. 3-MeAde was determined as the mono-tert-butyldimethylsilyl derivative and quantitated by measurement of ions at m/z 206 (3-MeAde-d0) and m/z 209 (3-MeAde-d3). Repeated analyses of a human urine sample show excellent reproducibility of the method.

The determination of urinary 3-methyladenine by immunoaffinity chromatography-monoclonal antibody-based ELISA: use in human biomonitoring studies.

A mouse monoclonal antibody (Mab) was prepared which showed high specificity for a potential marker of exposure to methylating carcinogens such as 3-methyladenine (3-MeAde). In a low-temperature (4 degrees C) ELISA a linear calibration curve was obtained between 3 and 50 fmol/well. In combination with an immunoaffinity (IA) column prepared from a 3-MeAde rabbit antiserum, the ELISA was used to determine 3-MeAde in urine. The IA-ELISA method was validated by comparison with results obtained by an IA-GC-MS method. The effect of consuming a low 3-MeAde diet on urinary 3-MeAde excretion was investigated in a human volunteer. Urine collected during a 'normal' diet exhibited the characteristic variation in 3-MeAde levels previously observed (9.5 micrograms/24 h, SD = 4.4, n = 5). In contrast, 3-MeAde excretion was markedly lower and less variable on days when the diet was closely controlled (0.63 microgram/24 h, SD = 0.08, n = 3). Dietary intake of 3-MeAde on the latter days was between 0.37 and 0.43 microgram/day, indicating that most, if not all, of the 3-MeAde seen in previous experiments was derived from the diet. The origin of dietary 3-MeAde is not known, but may be related to fumigant use. Dietary manipulation affords the possibility of carrying out model studies, in volunteers, on 3-MeAde intake and formation in vivo.