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BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).
Assuntos
Neoplasias da Mama/terapia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Qualidade de VidaRESUMO
PURPOSE: Exercise levels often decline following cancer diagnosis despite growing evidence of its benefits. Treatment side effects, older age, lack of confidence and opportunity to exercise with others in similar circumstances influence this. Our study explored the experiences of people attending a cancer-specific community-based exercise programme (CU Fitter™). METHODS: A survey distributed to those attending the programme gathered demographic/clinical information, self-reported exercise levels, information provision and barriers to/benefits of exercise. RESULTS: Sixty surveys were evaluable from 65/100 returned (62% female, 68% > 60 years, 66% breast/prostate cancer). Most (68%) were receiving treatment. Sixty-eight percent attended classes once or twice weekly. Fifty-five percent received exercise advice after diagnosis, usually from their hospital doctor/nurse. More (73%) had read about exercising, but less used the Internet to source information (32%). Self-reported exercise levels were higher currently than before diagnosis (p = 0.05). Forty-eight percent said their primary barrier to exercising was the physical impact of cancer/treatment. Improving fitness/health (40%) and social support (16%) were the most important gains from the programme. Many (67%) had made other lifestyle changes and intented to keep (50%) or increase (30%) exercising. CONCLUSIONS: This community-based cancer-specific exercise approach engaged people with cancer and showed physical, psychological, and social benefits. IMPLICATIONS FOR CANCER SURVIVORS: Community-grown exercise initiatives bring cancer survivors together creating their own supportive environment. Combining this with instructors familiar with the population and providing an open-ended service may prove particularly motivating and beneficial. Further work is required to provide evidence for this.
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Sobreviventes de Câncer/psicologia , Terapia por Exercício/psicologia , Neoplasias/reabilitação , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Recent data indicate beneficial effects of treating grains with lactic acid (LA) in alleviating the need for inorganic phosphorus supplementation during ruminal fermentation in vitro. The aim of this study was to evaluate the effects of feeding concentrates treated with LA with or without inorganic phosphorus supplementation on feed intake, performance, blood variables, and reticuloruminal pH in dairy cows. A total of 16 early-lactating cows (12 Simmental and 4 Brown Swiss) were included in this study from d 1 until d 37 postpartum. Cows were fed 3 total mixed rations differing in supplementation of inorganic phosphorus and treatment of concentrates. The control (CON) and LA (+P) diets included a concentrate mixture containing 0.8% monocalcium phosphate, and the LA (-P) diet contained no inorganic phosphorus source. The concentrates of the LA (+P) and LA (-P) diets were treated with 5% LA for 24h before feeding, and the concentrate of the CON diet was not treated. Dry matter intake and milk yield were recorded daily, and milk composition and blood variables were determined on several occasions during the trial. Reticuloruminal pH was measured using indwelling sensors that allowed for continuous measurement during the experimental period. Data showed depressed dry matter intake in cows receiving LA-treated concentrates, but milk yield, body weight, and body weight changes remained similar among treatment groups. Cows receiving the LA-treated diets had lower concentrations of serum nonesterified fatty acids, cholesterol, and insulin, and they tended to have higher serum phosphorus levels. On the other hand, reticuloruminal pH was lower and duration of the pH being <6.0 was longer in cows in the LA-treated groups. Aspartate aminotransferase, gamma-glutamyltransferase, and concentrations of bilirubin and bile acids were lower in the LA (-P) group. Taken together, the 5% LA-treated diet without inorganic phosphorus supplementation did not exert any negative effects on performance. The observed beneficial effects on blood metabolites related to lipid metabolism, insulin sensitivity, and liver variables, as well as the tendency for greater systemic phosphorus circulation, suggest that diets including concentrates treated with 5% LA may allow for savings of inorganic phosphorus supplementation in dairy cows. Treatment with 5% LA enhanced cows' risk of developing subacute rumen acidosis, although this condition showed no adverse effects with respect to liver variables and the inflammatory response.
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Ração Animal/análise , Ácido Láctico/química , Fósforo/química , Rúmen/metabolismo , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/sangue , Bilirrubina/sangue , Peso Corporal , Bovinos , Colesterol/sangue , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos não Esterificados/sangue , Concentração de Íons de Hidrogênio , Insulina/sangue , Lactação , Ácido Láctico/sangue , Metabolismo dos Lipídeos , Leite/metabolismo , Fósforo/sangue , gama-Glutamiltransferase/sangueRESUMO
The present study aimed to investigate changes in the reticuloruminal pH and temperature dynamics in periparturient dairy cows. Reticuloruminal pH and temperature measurements were conducted from 7 d before until 8 d after parturition using indwelling sensors. Nine Simmental and 4 Brown Swiss dairy cows were fed a close-up total mixed ration (52.5% neutral detergent fiber, 5.68MJ of net energy for lactation per kg of dry matter) with additional 1kg/cow per d concentrate mixture (29.5% neutral detergent fiber and 6.25MJ of net energy for lactation per kg of dry matter), starting from 2 wk before the estimated calving date. Postpartum, all cows had free access to the same close-up diet and were gradually fed increasing amounts of a concentrate-rich total mixed ration for early-lactation cows (32.7% neutral detergent fiber, 7.22MJ of net energy for lactation per kg of dry matter). Data showed depressed reticuloruminal pH early postpartum, but only in the group of cows defined as subacute ruminal acidosis (SARA) susceptible (n=8), which had a higher duration time of pH <5.8 (753±82min/d) compared with SARA-tolerant cows (n=5; 15±6min/d). Also, compared with SARA-tolerant cows (112±91min/d), the SARA-susceptible group showed longer (1,049±75min/d) duration time of pH <6.0. When compared by breed, mean reticuloruminal pH tended to be lower in Simmental (6.16±0.03) than in Brown Swiss cows (6.25±0.05), but no differences were observed in the duration of pH <5.8 between breeds. Simmental cows produced more milk (30.4±1.2kg/d) compared with Brown Swiss cows (27.9±1.3kg/d). Neither total dry matter intake nor milk yield were different between SARA-susceptible and SARA-tolerant groups. However, SARA-tolerant cows consumed greater amounts of the close-up total mixed ration than their SARA-susceptible counterparts, whereas no difference was observed in the intake of the early-lactating total mixed ration between the groups. Reticuloruminal temperature was not affected by breed or SARA susceptibility. Interestingly, the mean reticuloruminal temperature and the time duration of temperature >39.5°C abruptly dropped from d 2 to 1 before calving by 0.35°C and 430min/d, respectively. In conclusion, the strong inter-animal variation in reticuloruminal pH responses suggests the need for more careful monitoring and differentiated feeding management of cows during the transition period, whereby the SARA-susceptible cows may require particular attention regarding feeding management and diet composition. The abrupt decrease in reticuloruminal temperature the day before parturition may enable this noninvasive method as a management tool for prediction of parturition time.
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Acidose/veterinária , Temperatura Corporal/fisiologia , Doenças dos Bovinos/fisiopatologia , Parto/fisiologia , Rúmen/química , Gastropatias/veterinária , Animais , Bovinos , Dieta/veterinária , Fibras na Dieta , Suscetibilidade a Doenças/veterinária , Feminino , Concentração de Íons de Hidrogênio , Lactação/fisiologia , Leite/química , Tamanho da Partícula , Gastropatias/fisiopatologiaRESUMO
Recent data indicate positive effects of treating grain with citric (CAc) or lactic acid (LAc) on the hydrolysis of phytate phosphorus (P) and fermentation products of the grain. This study used a semicontinuous rumen simulation technique to evaluate the effects of processing of barley with 50.25 g/L (wt/vol) CAc or 76.25 g/L LAc on microbial composition, metabolic fermentation profile, and nutrient degradation at low or high dietary P supply. The low P diet [3.1g of P per kg of dry matter (DM) of dietary P sources only] was not supplemented with inorganic P, whereas the high P diet was supplemented with 0.5 g of inorganic P per kg of DM through mineral premix and 870 mg of inorganic P/d per incubation fermenter via artificial saliva. Target microbes were determined using quantitative PCR. Data showed depression of total bacteria but not of total protozoa or short-chain fatty acid (SCFA) concentration with the low P diet. In addition, the low P diet lowered the relative abundance of Ruminococcus albus and decreased neutral detergent fiber (NDF) degradation and acetate proportion, but increased the abundance of several predominantly noncellulolytic bacterial species and anaerobic fungi. Treatment of grain with LAc increased the abundance of total bacteria in the low P diet only, and this effect was associated with a greater concentration of SCFA in the ruminal fluid. Interestingly, in the low P diet, CAc treatment of barley increased the most prevalent bacterial group, the genus Prevotella, in ruminal fluid and increased NDF degradation to the same extent as did inorganic P supplementation in the high P diet. Treatment with either CAc or LAc lowered the abundance of Megasphaera elsdenii but only in the low P diet. On the other hand, CAc treatment increased the proportion of acetate in the low P diet, whereas LAc treatment decreased this variable at both dietary P levels. The propionate proportion was significantly increased by LAc at both P levels, whereas butyrate increased only with the low P diet. Treatments with CAc or LAc reduced the degradation of CP and ammonia concentration compared with the control diet at both P levels. In conclusion, the beneficial effects of CAc and LAc treatment on specific ruminal microbes, fermentation profile, and fiber degradation in the low P diet suggest the potential for the treatment to compensate for the lack of inorganic P supplementation in vitro. Further research is warranted to determine the extent to which the treatment can alleviate the shortage of inorganic P supplementation under in vivo conditions.
Assuntos
Ácido Cítrico/análise , Grão Comestível , Microbioma Gastrointestinal/efeitos dos fármacos , Ácido Láctico/análise , Fósforo na Dieta/análise , Rúmen/microbiologia , Acetatos/análise , Ração Animal/análise , Animais , Dieta/veterinária , Fibras na Dieta/análise , Ácidos Graxos Voláteis/análise , Fermentação , Hordeum , Concentração de Íons de Hidrogênio , Megasphaera/isolamento & purificação , Prevotella/isolamento & purificação , Rúmen/efeitos dos fármacosRESUMO
The reaction of Criegee intermediates with a number of coreactants is examined using theoretical methodologies, combining ROCCSD(T)//M06-2X quantum calculations with theoretical kinetic predictions of the rate coefficients. The reaction of CI with alkenes is found to depend strongly on the substitutions in the reactants, resulting in significant differences in the predicted rate coefficient as a function of the selected alkene and CI. Despite submerged barriers, these entropically disfavored reactions are not expected to affect CI chemistry. The reaction of H2COO + H2COO is found to be barrierless, with a rate coefficient nearing the collision limit, ≥4 × 10(-11) cm(3) molecule(-1) s(-1). The dominant reaction products are expected to be carbonyl compounds and an oxygen molecule, though chemically activated reactions may give rise to a plethora of different (per)acids and carbonyl compounds. CI + CI reactions are expected to be important only in laboratory environments with high CI concentrations. The reaction of H2COO with O3 was predicted to proceed through a pre-reactive complex and a submerged barrier, with a rate coefficient of 1 × 10(-12) cm(3) molecule(-1) s(-1). A study of the dominant CI reactions under experimental and atmospheric conditions shows that the latter reaction might affect CI chemistry.
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The syn-CH3CHOO Criegee intermediate formed from the ozonolysis of propene and (E)-2-butene was detected via unimolecular decomposition and subsequent detection of OH radicals by a LIF-FAGE instrument. An observed time dependent OH concentration profile was analysed using a detailed model focusing on the speciated chemistry of Criegee intermediates based on the recent literature. The absolute OH concentration was found to depend on the steady state concentration of syn-CH3CHOO at the injection point while the time dependence of the OH concentration profile was influenced by the sum of the rates of unimolecular decomposition of syn-CH3CHOO and wall loss. By varying the most relevant parameters influencing the SCI chemistry in the model and based on the temporal OH concentration profile, the unimolecular decomposition rate k (293 K) of syn-CH3CHOO was shown to lie within the range 3-30 s(-1), where a value of 20 ± 10 s(-1) yields the best agreement with the CI chemistry literature.
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Terrestrial vegetation, especially tropical rain forest, releases vast quantities of volatile organic compounds (VOCs) to the atmosphere, which are removed by oxidation reactions and deposition of reaction products. The oxidation is mainly initiated by hydroxyl radicals (OH), primarily formed through the photodissociation of ozone. Previously it was thought that, in unpolluted air, biogenic VOCs deplete OH and reduce the atmospheric oxidation capacity. Conversely, in polluted air VOC oxidation leads to noxious oxidant build-up by the catalytic action of nitrogen oxides (NO(x) = NO + NO2). Here we report aircraft measurements of atmospheric trace gases performed over the pristine Amazon forest. Our data reveal unexpectedly high OH concentrations. We propose that natural VOC oxidation, notably of isoprene, recycles OH efficiently in low-NO(x) air through reactions of organic peroxy radicals. Computations with an atmospheric chemistry model and the results of laboratory experiments suggest that an OH recycling efficiency of 40-80 per cent in isoprene oxidation may be able to explain the high OH levels we observed in the field. Although further laboratory studies are necessary to explore the chemical mechanism responsible for OH recycling in more detail, our results demonstrate that the biosphere maintains a remarkable balance with the atmospheric environment.
Assuntos
Atmosfera/química , Árvores/metabolismo , Clima Tropical , Animais , Oceano Atlântico , Butadienos/metabolismo , Guiana Francesa , Guiana , Hemiterpenos/metabolismo , Radical Hidroxila/metabolismo , Óxido Nítrico/metabolismo , Oxirredução , Ozônio/análise , Pentanos/metabolismo , SurinameRESUMO
BACKGROUND: As few older women with breast cancer receive adjuvant chemotherapy, we examined the barriers and perceptions of 24 UK NHS multidisciplinary breast cancer teams to offering this treatment to women ≥70 years. PATIENTS AND METHODS: Questionnaires regarding 803 patients with newly diagnosed breast cancer were completed by specialist teams following discussion or outpatient consultation. RESULTS: Of 803 patients, 116 (14%), all <85 years, were offered chemotherapy and 66 (8%) received it. Only 94 of 309 (30%) of women with high-risk disease were offered chemotherapy, and 53 (17%) received it. The most common reasons for not offering chemotherapy were 'other treatments more appropriate' (usually patients with ER-positive tumours) or 'benefits too small' (63% and 54% of patients, respectively). Co-morbidities and frailty were less common reasons but became more frequent with increasing age. Recommendations regarding chemotherapy were made in the absence of documented HER2 and performance status in 29% and 33%, respectively. Treatment offered varied considerably between cancer centres. CONCLUSIONS: National guidelines need development describing the minimally acceptable data for decision making, incorporating objective fitness measures and specific treatment recommendations. Such guidelines will require educational support for implementation but should standardise care and improve chemotherapy uptake in this increasing population of older patients.
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Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Tomada de Decisões , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Corpo Clínico , Inquéritos e Questionários , Suspensão de TratamentoRESUMO
The reaction of Criegee intermediates (CI) with NO and RO(2) radicals is studied for the first time by theoretical methodologies; additionally, the reaction of CI with SO(2) molecules is re-examined. The reaction of CI with NO was found to be slow, with a distinct energy barrier. Their reaction with RO(2) radicals proceeds by the formation of a pre-reactive complex followed by addition of the RO(2) radical on the CI carbon over a submerged barrier, leading to a larger peroxy radical and opening the possibility for oligomer formation in agreement with experiment. The impact of singlet biradicals on the reaction of CI with SO(2) is examined, finding a different reaction mechanism compared to earlier work. For larger CI, the reaction with SO(2) at atmospheric pressures mainly yields thermalized sulfur-bearing secondary ozonides. The fate of the CI in the atmosphere is examined in detail, based on observed concentration of a multitude of coreactants in the atmosphere, and estimated rate coefficients available from literature data. The impact of SCI on tropospheric chemistry is discussed.
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Atmosfera/química , Óxido Nítrico/química , Compostos Orgânicos/química , Dióxido de Enxofre/químicaRESUMO
PURPOSE: Yoga is increasingly used as a complementary therapy to manage disease and treatment-related side effects in patients with cancer and has resulted in an increase in the number of studies exploring the effectiveness of yoga interventions. This systematic review examines whether yoga interventions provide any measurable benefit, both physically and psychologically, for women with breast cancer. The results will inform future research in this field and advance the development of yoga programmes. METHODS: We performed electronic searches of MEDLINE, PsychINFO, the Cochrane Library, Embase, CINAHL, AMED, Web of Science and Scopus for articles published up to June 2012. Only randomised controlled trials (RCTs) were included and methodological quality rating scores were determined using the PEDro (Physiotherapy Evidence Database) Scale. RESULTS: One hundred thirty-two studies were identified through a systematic search of eight electronic databases. Only published manuscripts that employed a RCT design were included (n = 18). The sample sizes for these studies varied widely from 18 to 164 participants and the associated PEDro scores ranged from 1 (poor) to 8 (good). All 18 studies reported positive effects for treatment-related side effects in favour of the yoga interventions, with the greatest impact on global quality of life (QoL) scores and emotional well-being. CONCLUSION: Results from the few RCTs suggest there is moderate to good evidence that yoga may be a useful practice for women recovering from breast cancer treatments. Large-scale RCTs using objective measures and patient-reported outcomes with long-term follow-up are needed to substantiate whether the benefits are true and sustainable.
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Neoplasias da Mama/psicologia , Fadiga/terapia , Terapias Mente-Corpo/métodos , Náusea/terapia , Yoga , Afeto , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Fadiga/complicações , Feminino , Humanos , Náusea/complicações , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: The relationship between HIV and cervical cancer is well established. Interventions that focus on creating human papillomavirus (HPV) vaccine and cervical cancer prevention messaging for adolescents, caregivers and educators will increase uptake of HPV vaccinations, HPV testing and cervical cancer screening for high-risk adolescent girls and young women (AGYW). In order to effectively develop appropriate interventions, it is important to examine AGYW's perceptions regarding their personal risk of acquiring HPV, as well as vaccine acceptability. OBJECTIVES: To measure the level of perceived personal risk of acquiring HPV and developing cervical cancer; examine the sociodemographic and behavioural factors associated with perceived risk; and assess HPV vaccine acceptability. METHODS: AGYW aged 16 - 24 years participating in the AYAZAZI study in Durban, South Africa (SA), were invited to participate in the AYA-HPV Prevention Project (AHPP), and were administered a questionnaire that assessed HPV, cervical cancer and vaccine awareness and knowledge, self-perceived HPV and cervical cancer risk, HPV vaccine uptake and acceptability, and participation in cervical cancer screening. The questionnaire measured self-perceived risk of acquiring HPV and developing cervical cancer for the respondent and other young women, as well as vaccine acceptability. Data from the main AYAZAZI study (12-month) visit were linked to AHPP substudy data. Descriptive statistics were used to analyse sociodemographic variables at the 12-month time point. Self-perceived HIV, HPV and cervical cancer risk was measured using an ordinal scale. Chi-square analyses were used to examine differences in sociodemographic and behavioural factors according to self-perceived risk of HPV and cervical cancer. RESULTS: Only a small portion of participants (14.3%) had heard of HPV. Overall, 43.0% (n=49) perceived themselves as at low HPV risk. There were significant differences in self-perceived risk of cervical cancer by age group, income and pregnancy status. The highest proportion of AGYW who perceived themselves as at high risk of cervical cancer reported being sexually active (p=0.002). Although many participants reported not knowing about HPV prior to the study, after learning about it during the study, most said that they would be willing to receive the vaccine (97.5%). CONCLUSIONS: Most young women in SA do not have access to the national HPV vaccine programme, as only girls in grade 4 in some public schools qualify. Almost all participants indicated that if the vaccine was free and recommended by a healthcare professional, they would accept it. Availability of the HPV vaccine and timely treatment of HPV infections are key issues to address in efforts to decrease cervical cancer worldwide.
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Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Fatores Etários , Detecção Precoce de Câncer , Feminino , Humanos , Renda , Infecções por Papillomavirus/complicações , Aceitação pelo Paciente de Cuidados de Saúde , Percepção , Fatores de Risco , Comportamento Sexual , África do Sul , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Air pollution is growing fastest in monsoon-affected South Asia. During the dry winter monsoon, the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the Oxidation Mechanism Observations campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism by which contaminants are rapidly oxidized and deposited to Earth's surface. However, some pollutants are lofted above the monsoon clouds and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.
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Poluentes Atmosféricos/química , Poluição do Ar , Vento , Ásia , Modelos Teóricos , Estações do AnoRESUMO
Cisplatin has been shown to create interstrand DNA crosslinks by several methods. These experiments were performed to determine if cisplatin coordinates cross-links between deoxyguanylic and deoxycytidylic acids. After incubation at pH 7.2 with cisplatin at various platinum/base nucleotide ratios, ri, for 3 days at 20 degrees, polydeoxyguanylic acid . polydeoxycytidylic acid [poly(dG) . poly(dC)] was centrifuged in alkaline cesium sulfate for 3 days at 35,000 rpm. Untreated samples resulted in a low-density deoxycytidylic acid peak and a high-density deoxyguanylic acid peak, as identified by the ultraviolet absorption spectrum. The density gradient profiles of cisplatin-treated poly(dG). poly(dC) had an additional hybrid-density peak the area of which increased with the dose (ri) as the areas under the polydeoxycytidylic acid [poly(dC)] and polydeoxyguanylic acid [poly(dG)] peaks diminished. With increasing ri, the densities of both the poly(dG) and hybrid peaks increased while that of the poly(dC) peak remained unchanged. Similarly, the amount of bound platinum in the poly(dG) and hybrid-density peaks increased with ri, while no platinum could be detected in the poly(dC) peak. Therefore, cisplatin appears to react first with the deoxyguanylic acid strand, followed by a second reaction with the deoxycytidylic acid strand to form the interstrand cross-links that are necessary for the formation of the hybrid-density bands. Based upon the intercept of the percent cross-linked poly(dG) . poly(dC) versus ri curve with the abscissa, the minimum amount of cisplatin or the threshold amount of cisplatin required to observe cross-links was ri = 0.017. When multiplied by the molecular weight of the poly(dG) . poly(dC) used, this was equivalent to 1 cross-link per 15 molecules of bound platinum. However, based upon the amount of bound drug, the frequency of cross-links per platinum reaction was calculated to range from one of 50 to 67 reactions. Due to limitations in the sensitivity of the platinum assay and to a progressively lower recovery of the cross-linked material at lower ri values, it was not possible to calculate the cross-linking efficiency based upon the amount of bound drug for ri values equal to or less than 0.025. The monofunctional analogue, [diethylenetriaminechloroplatinum] chloride, did not cause a hybrid peak to form. These studies demonstrate that cisplatin coordinates interstrand cross-links between poly(dG) and poly(dC).
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Cisplatino/farmacologia , Poli C/metabolismo , Poli G/metabolismo , Polidesoxirribonucleotídeos/metabolismo , Polirribonucleotídeos/metabolismo , Centrifugação com Gradiente de ConcentraçãoRESUMO
BACKGROUND: The prevention of work disability is beneficial to employees and employers, and mitigates unnecessary societal costs associated with social welfare. Many service providers and employers have initiated workplace interventions designed to reduce unnecessary work disability. OBJECTIVE: To conduct a best-evidence synthesis of systematic reviews on workplace interventions that address physical activities or exercise and their impact on workplace absence, work productivity or financial outcomes. METHODS: Using a participatory research approach, academics and stakeholders identified inclusion and exclusion criteria, built an abstraction table, evaluated systematic review quality and relevance, and interpreted the combined findings. A minimum of two scientists participated in a methodological review of the literature followed by a consensus process. RESULTS: Stakeholders and researchers participated as a collaborative team. 3363 unique records were identified, 115 full text articles and 46 systematic reviews were included, 18 assessed the impact of physical fitness or exercise interventions. 11 focused on general workers rather than workers who were absent from work at baseline; 16 of the reviews assessed work absence, 4 assessed productivity and 6 assessed financial impacts. CONCLUSION: The strongest evidence supports the use of short, simple exercise or fitness programs for both workers at work and those absent from work at baseline. For workers at work, simple exercise programs (1-2 modal components) appear to provide similar benefits to those using more complex multimodal interventions. For workers off-work with subacute low back pain, there is evidence that some complex exercise programs may be more effective than simple exercise interventions, especially if they involve workplace stakeholder engagement, communication and coordination with employers and other stakeholders. The development and utilization of standardized definitions, methods and measures and blinded evaluation would improve research quality and strengthen stakeholder-centered guidance.
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Absenteísmo , Eficiência , Exercício Físico , Saúde Ocupacional , Local de Trabalho , Medicina Baseada em Evidências , Humanos , Dor Lombar/prevenção & controle , Local de Trabalho/economiaRESUMO
BACKGROUND: Mental health issues in the workplace are a growing concern among organizations and policymakers, but it remains unclear what interventions are effective in preventing mental health problems and their associated organizational consequences. This synthesis reports on workplace mental health interventions that impact absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the level of evidence supporting mental health interventions as valuable to work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO and TRIP. Grey literature searches included health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. The assessment of articles for inclusion criteria and methodological quality was conducted independently by two or more researchers, with differences resolved through consensus. RESULTS: The search resulted in 3363 titles, of which 3248 were excluded following title/abstract review, with 115 articles retrieved for full-text review. 14 articles finally met the inclusion criteria and are summarized in this synthesis. CONCLUSION: There is moderate evidence for the effectiveness of workplace mental health interventions on improved workplace outcomes. Certain types of programs, such as those incorporating both mental and physical health interventions, multicomponent mental health and/or psychosocial interventions, and exposure in vivo containing interventions for particular anxiety disorders had a greater level of research evidence to support their effectiveness.
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Serviços de Saúde Mental , Absenteísmo , Humanos , Saúde Mental/economia , Trabalho/psicologia , Local de Trabalho/economia , Local de Trabalho/psicologiaRESUMO
BACKGROUND: There is controversy surrounding the impact of workplace interventions aimed at improving social support and supervisory quality on absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the value of social support interventions for work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012 to complete a synthesis of systematic reviews guided by the PRISMA statement and the IOM guidelines for systematic reviews. Assessment of articles for inclusion and methodological quality was conducted independently by at least two researchers, with differences resolved by consensus. RESULTS: The search resulted in 3363 titles of which 3248 were excluded following title/abstract review, leaving 115 articles that were retrieved and underwent full article review. 10 articles met the set inclusion criteria, with 7 focusing on social support, 2 on supervisory quality and 1 on both. We found moderate and limited evidence, respectively, that social support and supervisory quality interventions positively impact workplace outcomes. CONCLUSION: There is moderate evidence that social support and limited evidence that supervisory quality interventions have a positive effect on work outcomes.
Assuntos
Apoio Social , Local de Trabalho/estatística & dados numéricos , Absenteísmo , Adolescente , Adulto , Idoso , Humanos , Metanálise como Assunto , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Literatura de Revisão como Assunto , Trabalho/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Physical and psychological job demands in combination with the degree of control a worker has over task completion, play an important role in reducing stress. Occupational stress is an important, modifiable factor affecting work disability. However, the effectiveness of reducing job demands or increasing job control remains unclear, particularly for outcomes of interest to employers, such as absenteeism or productivity. OBJECTIVE: This systematic review reports on job demand and control interventions that impact absenteeism, productivity and financial outcomes. METHODS: A stakeholder-centered best-evidence synthesis was conducted with researcher and stakeholder collaboration throughout. Databases and grey literature were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO, TRIP, health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. Articles were assessed independently by two researchers for inclusion criteria and methodological quality. Differences were resolved through consensus. RESULTS: The search resulted in 3363 unique titles. After review of abstracts, 115 articles were retained for full-text review. 11 articles finally met the inclusion criteria and are summarized in this synthesis. The best level of evidence we found indicates that multimodal job demand reductions for either at-work or off-work workers will reduce disability-related absenteeism. CONCLUSION: In general, the impacts of interventions that aim to reduce job demands or increase job control can be positive for the organization in terms of reducing absenteeism, increasing productivity and cost-effectiveness. However, more high quality research is needed to further assess the relationships and quantify effect sizes for the interventions and outcomes reviewed in this study.
Assuntos
Absenteísmo , Eficiência Organizacional , Satisfação no Emprego , Estresse Fisiológico , Estresse Psicológico , Análise Custo-Benefício , Humanos , Local de Trabalho/psicologiaRESUMO
In a patient with nephrotic syndrome, renal biopsy revealed AL amyloid deposits. Monoclonal lambda light chains were identified in serum and urine. A low percentage of monoclonal plasma cells was detected in the bone marrow. The patient received four cycles of VAD and subsequent high-dose chemotherapy (HDCT) with melphalan (200 mg/m2) followed by autologous peripheral blood stem cell transplantation. Proteinuria rapidly diminished during chemotherapy. Three months after HDCT, the patient has no edema, and no signs of plasma cell dyscrasia are currently detectable. Using VAD before starting HDCT may improve the condition of patients with amyloidosis and reduce transplantation-related morbidity and mortality.
Assuntos
Amiloidose/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Melfalan/uso terapêutico , Síndrome Nefrótica , Terapia Combinada , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/fisiopatologia , Síndrome Nefrótica/terapia , Recidiva , Transplante Autólogo , Vincristina/uso terapêuticoRESUMO
The effects of cis dichlorodiammine platinum [cis Pt(II)], trans dichlorodiammine platinum (trans Pt(II)], cis tetrachlorodiammine platinum [cis Pt(IV)], trans tetrachlorodiammine platinum [trans Pt(IV)], and ethylenediaminedichloride platinum [Pt(II)en] on the absorption spectra, and thermal hyper- and hypochromicity of calf thymus DNA were investigated. Platinum-induced renaturation was studied as one parameter of interstrand cross-linking. Based on a DNA cross-linking hypothesis, the tumor-inhibitory platinum compounds cis Pt(II), cis Pt(IV) and Pt(II)en would be expected to induce renaturation following thermal denaturation, whereas the ineffective drugs, trans Pt(II) and trans Pt(IV) would not. All five bind to DNA in such a way as to induce renaturation. However, cis Pt(IV) requires at least a 3- to 4-fold longer incubation time than is required by the other compounds to form the coordination bonds necessary for renaturation. Maximum renaturation with all compounds was observed at a molar Pt/base ratio of 0.05 except cis Pt(IV), with which it was 0.25. The rate of the formation of the platinum-coordinated cross-links by fresh cis Pt(II) suggests two reactions or types of reactions occur. The first is rapid and destabilizes the DNA helix, whereas the second is slow and responsible for renaturation following thermal denaturation. These results suggest that cis Pt(IV) may be activated cellularly and that cross-linking is not the primary mechanism of action of the tumor-inhibitory platinum compounds.