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PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.
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BACKGROUND: Migrants and refugees/asylum seekers, as a large part of the European work force, are often confronted with unfavorable working conditions in the host country. Main aim of this systematic review was to compare the association of these working conditions with mental health between migrants and refugees/asylum seekers due to their diverse migration experiences and cultural origins, and between different European host countries. METHODS: Systematic search for eligible primary studies was conducted in three electronic databases (PubMed/MEDLINE, PsycINFO and CINAHL) using quantitative study designs written in English, German, French, Italian, Polish, Spanish or Turkish and published from January 1, 2016 to October 27, 2022. Primary health outcomes were diagnosed psychiatric and psychological disorders, suicide and suicide attempts, psychiatric and psychological symptoms, and perceived distress. Secondary health outcomes were more general concepts of mental health such as well-being, life satisfaction and quality of life. Two reviewers independently completed screening, data extraction and the methodological quality assessment of primary studies using the Newcastle-Ottawa-Scale. Descriptive summary of primary studies on working conditions and their relationship with mental health were conducted, comparing migrants and refugees/asylum seekers, migrants and refugees/asylum seekers of different cultural backgrounds (collectivistic and individualistic) and migrants and refugees/asylum seekers living in different host countries. RESULTS: Inclusion criteria were met by 19 primary studies. Voluntary migrants are more likely to experience overqualification in the host country than refugees. In all examined host countries, migrants and refugees suffer from unfavorable working conditions, with migrants from collectivistic countries being slightly at risk compared to migrants from individualistic countries. Most unfavorable working conditions are related to poor mental health, regardless of migrant status, cultural origin or host country. CONCLUSIONS: Although the results should be interpreted with caution due to the small number of studies, it is evident that to maintain both the mental health and labor force of migrants and refugees/asylum seekers, their working conditions in host countries should be controlled and improved. Special attention should be paid to specific subgroups such as migrants from collectivistic societies. ETHICS AND DISSEMINATION: This systematic review is excluded from ethical approval because it used previously approved published data from primary studies. TRIAL REGISTRATION NUMBER: CRD42021244840.
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Refugiados , Migrantes , Lugar de Trabajo , Humanos , Europa (Continente)/epidemiología , Salud Mental , Calidad de Vida , Refugiados/psicologíaRESUMEN
BACKGROUND: Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues. OBJECTIVES: To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment. SEARCH METHODS: We searched 18 electronic databases, six websites, four mailing lists, and the reference lists of included studies and reviews. The last search dates were in February 2021 and November 2022. SELECTION CRITERIA: We included randomised controlled trials with individuals using drugs, alcohol, or both. Interventions were MI or motivational enhancement therapy (MET), delivered individually and face to face. Eligible control interventions were no intervention, treatment as usual, assessment and feedback, or other active intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, and assessed the certainty of evidence with GRADE. We conducted meta-analyses for the three outcomes (extent of substance use, readiness to change, retention in treatment) at four time points (post-intervention, short-, medium-, and long-term follow-up). MAIN RESULTS: We included 93 studies with 22,776 participants. MI was delivered in one to nine sessions. Session durations varied, from as little as 10 minutes to as long as 148 minutes per session, across included studies. Study settings included inpatient and outpatient clinics, universities, army recruitment centres, veterans' health centres, and prisons. We judged 69 studies to be at high risk of bias in at least one domain and 24 studies to be at low or unclear risk. Comparing MI to no intervention revealed a small to moderate effect of MI in substance use post-intervention (standardised mean difference (SMD) 0.48, 95% confidence interval (CI) 0.07 to 0.89; I2 = 75%; 6 studies, 471 participants; low-certainty evidence). The effect was weaker at short-term follow-up (SMD 0.20, 95% CI 0.12 to 0.28; 19 studies, 3351 participants; very low-certainty evidence). This comparison revealed a difference in favour of MI at medium-term follow-up (SMD 0.12, 95% CI 0.05 to 0.20; 16 studies, 3137 participants; low-certainty evidence) and no difference at long-term follow-up (SMD 0.12, 95% CI -0.00 to 0.25; 9 studies, 1525 participants; very low-certainty evidence). There was no difference in readiness to change (SMD 0.05, 95% CI -0.11 to 0.22; 5 studies, 1495 participants; very low-certainty evidence). Retention in treatment was slightly higher with MI (SMD 0.26, 95% CI -0.00 to 0.52; 2 studies, 427 participants; very low-certainty evidence). Comparing MI to treatment as usual revealed a very small negative effect in substance use post-intervention (SMD -0.14, 95% CI -0.27 to -0.02; 5 studies, 976 participants; very low-certainty evidence). There was no difference at short-term follow-up (SMD 0.07, 95% CI -0.03 to 0.17; 14 studies, 3066 participants), a very small benefit of MI at medium-term follow-up (SMD 0.12, 95% CI 0.02 to 0.22; 9 studies, 1624 participants), and no difference at long-term follow-up (SMD 0.06, 95% CI -0.05 to 0.17; 8 studies, 1449 participants), all with low-certainty evidence. There was no difference in readiness to change (SMD 0.06, 95% CI -0.27 to 0.39; 2 studies, 150 participants) and retention in treatment (SMD -0.09, 95% CI -0.34 to 0.16; 5 studies, 1295 participants), both with very low-certainty evidence. Comparing MI to assessment and feedback revealed no difference in substance use at short-term follow-up (SMD 0.09, 95% CI -0.05 to 0.23; 7 studies, 854 participants; low-certainty evidence). A small benefit for MI was shown at medium-term (SMD 0.24, 95% CI 0.08 to 0.40; 6 studies, 688 participants) and long-term follow-up (SMD 0.24, 95% CI 0.07 to 0.41; 3 studies, 448 participants), both with moderate-certainty evidence. None of the studies in this comparison measured substance use at the post-intervention time point, readiness to change, and retention in treatment. Comparing MI to another active intervention revealed no difference in substance use at any follow-up time point, all with low-certainty evidence: post-intervention (SMD 0.07, 95% CI -0.15 to 0.29; 3 studies, 338 participants); short-term (SMD 0.05, 95% CI -0.03 to 0.13; 18 studies, 2795 participants); medium-term (SMD 0.08, 95% CI -0.01 to 0.17; 15 studies, 2352 participants); and long-term follow-up (SMD 0.03, 95% CI -0.07 to 0.13; 10 studies, 1908 participants). There was no difference in readiness to change (SMD 0.15, 95% CI -0.00 to 0.30; 5 studies, 988 participants; low-certainty evidence) and retention in treatment (SMD -0.04, 95% CI -0.23 to 0.14; 12 studies, 1945 participants; moderate-certainty evidence). We downgraded the certainty of evidence due to inconsistency, study limitations, publication bias, and imprecision. AUTHORS' CONCLUSIONS: Motivational interviewing may reduce substance use compared with no intervention up to a short follow-up period. MI probably reduces substance use slightly compared with assessment and feedback over medium- and long-term periods. MI may make little to no difference to substance use compared to treatment as usual and another active intervention. It is unclear if MI has an effect on readiness to change and retention in treatment. The studies included in this review were heterogeneous in many respects, including the characteristics of participants, substance(s) used, and interventions. Given the widespread use of MI and the many studies examining MI, it is very important that counsellors adhere to and report quality conditions so that only studies in which the intervention implemented was actually MI are included in evidence syntheses and systematic reviews. Overall, we have moderate to no confidence in the evidence, which forces us to be careful about our conclusions. Consequently, future studies are likely to change the findings and conclusions of this review.
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Entrevista Motivacional , Trastornos Relacionados con Sustancias , Humanos , Entrevista Motivacional/métodos , Trastornos Relacionados con Sustancias/terapia , Factores de Tiempo , Motivación , AfectoRESUMEN
OBJECTIVE: Migrants and refugees/asylum seekers make up a significant proportion of the European workforce. They often suffer from poor working conditions, which might impact mental health. The main objective of this systematic review was to summarize and analyze existing research on working conditions of migrants and refugees/asylum seekers in European host countries and compare them to those of natives. Furthermore, the relationship between working conditions and mental health of migrants/refugees/asylum seekers and natives will be compared. METHODS: Three electronic databases (PubMed/MEDLINE, PsycInfo and CINAHL) were systematically searched for eligible articles using quantitative study designs written in English, German, French, Italian, Polish, Spanish or Turkish and published from January 1, 2016 to October 27, 2022. Primary health outcomes were diagnosed psychiatric and psychological disorders, suicide (attempts), psychiatric and psychological symptoms, and perceived distress. Secondary health outcomes were more general concepts of mental health such as well-being, life satisfaction and quality of life. Screening, data extraction and the methodological quality assessment of primary studies by using the Newcastle-Ottawa Scale were done independently by two reviewers. The results of the primary studies were summarized descriptively. Migrants and refugees/asylum seekers were compared with natives in terms of the association between working conditions and mental health. RESULTS: Migrants and refugees often face disadvantages at work concerning organizational (low-skilled work, overqualification, fixed-term contracts, shift work, lower reward levels) and social conditions (discrimination experiences) in contrast to natives. Most unfavorable working conditions are associated with worse mental health for migrants as well as for natives. CONCLUSIONS: Even if the results are to be taken with caution, it is necessary to control and improve the working conditions of migrants and refugees/asylum seekers and adapt them to those of the native population to maintain their mental health and thus their labor force.
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Refugiados , Migrantes , Humanos , Salud Mental , Refugiados/psicología , Calidad de Vida , Condiciones de Trabajo , Europa (Continente)/epidemiologíaRESUMEN
BACKGROUND: Tobacco, khat, alcohol, and marijuana are the main risk factors for non-communicable diseases. There are limited studies on substance use in Ethiopia, especially among secondary school students. This study aims to determine the epidemiology of substance use among secondary school students in Ethiopia. METHODS: This cross-sectional study was conducted in March 2020 in four large regions of Ethiopia and the capital Addis Ababa. We collected data from 3,355 grade 9 and grade 10 students in 36 randomly selected high schools. Data were collected on tobacco, khat, alcohol and other substances. Mixed effect logistic regression models were fitted to determine the predictors of cigarette smoking. RESULTS: 157 (4.7%) of the participants ever smoked cigarettes and 81 (2.4%) were current smokers. 106 (3.2%) ever used smokeless tobacco, 1,342 (41.8%) had ever drunk alcohol, 290 (8.7%) ever used khat, 137 (4.8%) chewed khat regularly and 76 (2.3%) ever used marijuana. There was a significant regional variation in substance use patterns; cigarette and khat use was the highest in southern regions, whereas alcohol use was highest in the northern areas. Availability of cigarette and khat shops within a 100-meter radius of the school compound was reported by 1,229 (37.5%) and 816 (25%) students, respectively. Three hundred fifty-four (10.9%) students had ever seen someone smoking a cigarette in the school compound. Ever use of smokeless tobacco (Adjusted Odds Ratio (AOR) = 9.4, 95%CI: 4.9-17.9), ever use of shisha (AOR = 8, 95% CI: 3.9-16.3), ever use of khat (AOR = 4.1, 95%CI: 2.5-6.8), ever use of alcohol (AOR = 2.3, 95%CI: 1.4-3.7), having a friend who smoked a cigarette (AOR = 2, 95%CI: 1.2-3.5), and ever seen someone smoking a cigarette in the school compound (AOR = 1.9, 95%CI: 1.1-3.4) were associated with ever use of cigarettes. CONCLUSION: Substance use prevalence in Ethiopia has regional variations and prevention strategies should be tailored to the needs of the regions. Although this study reported a lower prevalence of cigarette smoking, students could access cigarettes and khat in nearby school areas. The existing tobacco control laws that prohibit selling tobacco products to children and adolescents under 21 years of age and ban establishing tobacco shops close to school compounds should be enforced.
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Nicotiana , Trastornos Relacionados con Sustancias , Adolescente , Niño , Humanos , Catha/efectos adversos , Etiopía/epidemiología , Prevalencia , Estudios Transversales , Consumo de Bebidas Alcohólicas/epidemiología , Factores de Riesgo , Estudiantes , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
INTRODUCTION: Many women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients. METHODS AND MATERIALS: The 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment. RESULTS: A total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010). CONCLUSION: Breast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.
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Neoplasias de la Mama , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Etiopía , Femenino , Humanos , Cumplimiento de la Medicación , Tamoxifeno/uso terapéuticoRESUMEN
Outcome of allogeneic stem cell transplantation (alloSCT) is hampered by substantial non-relapse mortality (NRM). Given its impact on organ function and immune response, the nutritional status has been suggested as relevant for NRM. We aimed to evaluate the association of NRM with nutritional status prior to alloSCT and in the post-SCT course. In a retrospective single-center study, we analyzed 128 alloSCTs. Besides standard characteristics, nutrition-associated parameters BMI, serum total protein, and serum albumin were recorded before conditioning and at various time points after alloSCT. Association with NRM was evaluated by univariate and multivariate survival analysis. The cohort comprised patients with a median BMI of 26 kg/m2 (16.7-46.9 kg/m2), median serum total protein of 59 g/l (41-77 g/l), and serum albumin of 36 g/l (22-46 g/l) before SCT. NRM at d+100 was 14.8% and at 1 year 26.6%. Prior to SCT, only serum albumin deficiency was associated with increased NRM (p = .010) in multivariate analysis. After SCT (d+30 and d+100), all nutrition-associated parameters decreased (p < .002), but no association of deteriorating nutritional status with NRM was found. In multivariate analysis, serum albumin (p = .03) and severe albumin deficiency (p = .02) correlated with NRM at d+30 and d+100, while BMI and serum total protein did not. In our study, albumin deficiency, particularly prior to alloSCT, shows a strong correlation with NRM. This finding may add to monitoring, risk evaluation, and counseling of patients and serve as a rational for interventions to improve the nutritional status in patients undergoing SCT.
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Trasplante de Células Madre Hematopoyéticas , Estado Nutricional , Adulto , Anciano , Índice de Masa Corporal , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Albúmina Sérica/análisis , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: In Ethiopia, breast cancer is the leading cause of cancer among women. Little is known about the duration of disease and symptoms of patients who died from breast cancer in rural Ethiopia. The objective of this study was to assess breast cancer mortality with a particular focus on the self-reported duration of illness including suffering of symptoms, and need for medical care. METHODS: The cause of death was determined among randomly selected Ethiopian women residing in western Ethiopia. A modified standard verbal autopsy (VA) questionnaire was completed by women whose sisters had died. The questionnaires were reviewed by two independent local physicians to assign a cause of death. We analyzed pattern of cause of deaths, duration of suffering, symptoms, and treatment received. RESULT: In our study, the age at death was very similar to other population-based data from Ethiopia. We found 32% of 788 deaths were caused by communicable diseases, 12.1% by neoplasms, and 9.4% by pregnancy/maternal mortality. Breast cancer was the second leading neoplasm, responsible for 21 (2.7%) of all deaths (95% CI 1.5-3.7%), and was among the top five causes of non-communicable deaths. The median age of breast cancer death was 37 years, younger than for other causes of death. The median duration of illness with breast cancer was around 1 year. This was substantially more compared to the duration of infectious diseases, but less than the duration of reproductive neoplasms, diabetes, and epilepsy. DISCUSSION/CONCLUSION: Breast cancer deaths are common causes of death in women of rural Ethiopia. When assessing the total duration of illness according to specific causes of death, breast and other cancers accounted for a large share of the burden. This has practical implications and highlights the need for palliative care for cancer patients. Substantial efforts are necessary to improve early detection and treatment for breast cancer to reduce premature death in women.
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Neoplasias de la Mama , Adulto , Autopsia , Causas de Muerte , Etiopía/epidemiología , Femenino , Humanos , Morbilidad , EmbarazoRESUMEN
AIM OF THE STUDY: To outline basic information on communication structures and obstacles between GPs and nursing homes as well as GPs' perspectives on usage of E-health technology. METHODS: A questionnaire-based cross-sectional study carried out among n=600 randomly selected GPs in Germany sent by mail. RESULTS: The response rate was 20% (n=114). The respondent's mean age was 53 years (min=35; max=77), two-thirds were women (65%). GPs mainly used fax (92%) and telephone (87%) to communicate with nursing homes. Less than 10% routinely used digital technologies like E-mail (7%), E-health software (6%) or chat-services (1%). About half of GPs reported unnecessary (52%) or unspecific (51%) nursing home visit requests as well as unreported medication plan changes by other physicians (51%) as a common but avoidable problem. Many GPs wanted to use E-medication plans (85%), E-follow-up prescriptions (79%) and E-letters of referral (69%) in the future. 33% of GPs were already using fully digitalized patient files. Only 9% worked exclusively paper-based. CONCLUSION: Though GPs are open to digitalized communication with nursing homes, fax and telephone are still mostly used. GPs prefer to execute less complex tasks digitally, such as change of medication plans and letters of referral. Fewer can imagine digital solutions for complex procedures such as acute health problems and ward rounds. Only 8% do not want to work digitally at all.
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Médicos Generales , Adulto , Anciano , Actitud del Personal de Salud , Comunicación , Estudios Transversales , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Casas de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Oxygen (O2) is a drug with specific biochemical and physiologic properties, a range of effective doses and may have side effects. In 2015, 14â% of over 55â000 hospital patients in the UK were using oxygen. 42â% of patients received this supplemental oxygen without a valid prescription. Healthcare professionals are frequently uncertain about the relevance of hypoxemia and have low awareness about the risks of hyperoxemia. Numerous randomized controlled trials about targets of oxygen therapy have been published in recent years. A national guideline is urgently needed. METHODS: A S3-guideline was developed and published within the Program for National Disease Management Guidelines (AWMF) with participation of 10 medical associations. Literature search was performed until Feb 1st 2021 to answer 10 key questions. The Oxford Centre for Evidence-Based Medicine (CEBM) System ("The Oxford 2011 Levels of Evidence") was used to classify types of studies in terms of validity. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used and for assessing the quality of evidence and for grading guideline recommendation and a formal consensus-building process was performed. RESULTS: The guideline includes 34 evidence-based recommendations about indications, prescription, monitoring and discontinuation of oxygen therapy in acute care. The main indication for O2 therapy is hypoxemia. In acute care both hypoxemia and hyperoxemia should be avoided. Hyperoxemia also seems to be associated with increased mortality, especially in patients with hypercapnia. The guideline provides recommended target oxygen saturation for acute medicine without differentiating between diagnoses. Target ranges for oxygen saturation are depending on ventilation status risk for hypercapnia. The guideline provides an overview of available oxygen delivery systems and includes recommendations for their selection based on patient safety and comfort. CONCLUSION: This is the first national guideline on the use of oxygen in acute care. It addresses healthcare professionals using oxygen in acute out-of-hospital and in-hospital settings. The guideline will be valid for 3 years until June 30, 2024.
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Cuidados Críticos , Terapia por Inhalación de Oxígeno , Adulto , Humanos , Hipoxia/diagnóstico , Hipoxia/terapia , Oxígeno/uso terapéutico , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and leading cause of cancer deaths among women in low-income countries. Ethiopia does not have a national BC screening program, and over 80% of patients are diagnosed with advanced stage disease. The aim of this study was to assess how many women self-report a breast abnormality and to determine their diagnoses in rural Ethiopia. METHODS: A community-based cross-sectional study was conducted among 7,573 adult women. Women were interviewed and educated about breast awareness, and those who reported breast abnormalities underwent clinical examination by experienced surgeons. Ultrasound-guided fine needle aspiration cytology (FNAC) was obtained, and cytological analysis was performed. The findings were projected to the female population of Ethiopia to estimate current and future burden of diseases. FINDINGS: Of the 7,573 women surveyed, 258 (3.4%) reported a breast abnormality, 246 (3.2%) received a physical examination, and 49 (0.6%) were found to be eligible for ultrasound-guided FNAC or nipple discharge evaluation. Of all the cases, five (10.2%) breast malignancies were diagnosed. We projected for Ethiopia that, approximately, 1 million women could self-report a breast abnormality, 200,000 women could have a palpable breast mass, and 28,000 women could have BC in the country. CONCLUSION: The health care system needs to build capacity to assess and diagnose breast diseases in rural areas of Ethiopia. These data can be used for resource allocation to meet immediate health care needs and to promote detecting and treating BC at earlier stages of disease. IMPLICATIONS FOR PRACTICE: Routine mammography screening in a resource-limited country with a young population is neither sensitive nor affordable. Clinical breast examination with consecutive ultrasound-guided fine needle aspiration cytology may ensure early diagnosis, downstage disease, and reduce breast cancer mortality. This study had the unique opportunity to educate over 7,573 rural women about breast abnormalities and offer clinical and cytological diagnosis for reported breast abnormalities. The findings were extrapolated to show the nationwide burden of breast abnormalities and unmet diagnostic needs. These data will serve as policy guide to improve adequate referral mechanisms and breast diagnostic and treatment facilities.
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Neoplasias de la Mama , Adulto , Mama , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Estudios Transversales , Etiopía/epidemiología , Femenino , Humanos , AutoinformeRESUMEN
BACKGROUND: Osteopathy is a type of complementary medicine based on specific manual techniques. In many countries, including Germany, the profession is not officially regulated, and evidence for the effectiveness of osteopathy is insufficient for most diseases. Nevertheless, many health insurances in Germany offer reimbursement for therapy costs, if osteopathy is recommended by a physician. This cross-sectional survey of German general practitioners (GPs) explored beliefs and attitudes towards osteopathic medicine and described their daily interactions with it. METHODS: A random sample of 1000 GPs from all federal states was surveyed by mail using a self-designed questionnaire. We collected data on sociodemographics, personal experiences with osteopathy, and attitudes and expectations towards osteopathy. In particular, participants were asked about indications for osteopathic treatment and their beliefs about its effectiveness for different patient groups and diagnoses. A self-designed score was used to estimate general attitudes towards osteopathy and identify factors correlated with greater openness. Additionally, we performed logistic regression to reveal factors associated with the frequency of recommending osteopathy to patients. RESULTS: Response rate was 34.4%. 46.5% of participants were women, and the median age was 56.0 years. 91.3% of GPs had referred patients to an osteopath, and 88.0% had recommended osteopathy to their patients. However, 57.5% acknowledged having little or no knowledge about osteopathy. Most frequent reasons for a recommendation were spinal column disorders (46.2%), other complaints of the musculoskeletal system (18.2%) and headaches (9.8%). GPs estimated the highest benefit for chronically ill and middle-aged adults. Female gender (OR 2.09; 95%CI 1.29-3.38) and personal treatment experiences (OR 5.14; 95%CI 2.72-9.72) were independently positively associated with more frequent treatment recommendation. CONCLUSION: GPs in Germany have frequent contact with osteopathy, and the vast majority have recommended osteopathic treatment to some extent in their practice, with foci and opinions comparable to other Western countries. The discrepancy between GPs making frequent referrals for osteopathic treatment while self-assessing to have little knowledge about it demonstrates need for intensified research on the collaboration with osteopaths and how to best integrate osteopathic treatments. Our results may help to focus future effectiveness studies on most relevant clinical conditions in general practice.
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Médicos Generales , Medicina Osteopática , Adulto , Actitud , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Discontinuation of radiotherapy (RT) for cervical cancer (CC) in sub-Saharan Africa is common because of patient- and health service-related reasons. This analysis describes toxicities and the effect of adherence on survival. MATERIALS AND METHODS: A total of 788 patients with CC (2008-2012) who received RT at Addis Ababa University Hospital were included. External beam RT without brachytherapy was performed according to local guidelines. We previously described survival and prognostic factors. Now we analyzed adherence and survival according to total doses received. Adjustment via multivariate cox regression analysis was done. RESULTS: One-year overall survival (OS) after radical RT (n = 180) for International Federation of Gynecology and Obstetrics (FIGO) stages IIA-IIIA was 89% for discontinuation (<72 Gy) and 96% for adherence (≥72 Gy; hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.5-3.3). One-year OS after nonradical RT (n = 389) for FIGO stages IIIB-IVA was 71% for discontinuation (<40 Gy) and 87% for adherence (44-50 Gy; HR, 3.1; 95% CI, 1.4-6.9). One-year OS for FIGO stages IIIB-IVB (n = 219) after one compared with two or more palliative single fractions of 10 Gy were 14% and 73% respectively (HR, 7.3; 95% CI, 3.3-16). Reasons for discontinuation were toxicities, economic background, and RT machine breakdown. Grade 1-2 late toxicities were common (e.g., 30% proctitis, 22% incontinence). Grade 3 early and late toxicities were seen in 5% and 10% respectively; no grade 4 toxicities occurred. CONCLUSION: Patients who adhered to guideline-conforming RT had optimum survival. Better supportive care, brachytherapy to reduce toxicities, socioeconomic support, and additional radiation capacities could contribute to better adherence and survival. IMPLICATIONS FOR PRACTICE: This study presents the effect of adherence on survival of 788 patients with cervical cancer receiving external beam radiotherapy without brachytherapy in Ethiopia. Discontinuation of planned radiotherapy according to local guidelines considerably reduced survival for all International Federation of Gynecology and Obstetrics (FIGO) stages treated (hazard ratios were 1.3, 3.1, and 7.3 for FIGO stages IIA-IIIA and IIIB-IVA and the palliative approach, respectively). Early toxicity (5% grade 3) should be treated to improve adherence. Economic difficulties and machine breakdown should also be addressed to reduce discontinuation and improve survival.
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Neoplasias del Cuello Uterino/radioterapia , Adulto , Etiopía , Femenino , Humanos , Persona de Mediana Edad , Análisis de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are life-threatening conditions. While there is a broad body of evidence for the treatment of people with acute coronary syndrome under stable haemodynamic conditions, the treatment strategies for people who become haemodynamically unstable or develop CS remain less clear. We have therefore summarised here the evidence on the treatment of people with CS or LCOS with different inotropic agents and vasodilative drugs. This is the first update of a Cochrane review originally published in 2014. OBJECTIVES: To assess efficacy and safety of cardiac care with positive inotropic agents and vasodilator strategies in people with CS or LCOS due to AMI, HF or cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in people with myocardial infarction, heart failure or cardiac surgery complicated by cardiogenic shock or LCOS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 13 eligible studies with 2001 participants (mean or median age range 58 to 73 years) and two ongoing studies. We categorised studies into eight comparisons, all against cardiac care and additional other active drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and nitric oxide versus placebo.All trials were published in peer-reviewed journals, and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13 trials were small with few included participants. Acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements emerged in five of 13 trials. In general, confidence in the results of analysed studies was reduced due to serious study limitations, very serious imprecision or indirectness. Domains of concern, which show a high risk of more than 50%, include performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events.Levosimendan may reduce short-term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to 0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with moderate risk), NNT: 5 (patients with CS)). This initial short-term survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. There is uncertainty (due to lack of statistical power) as to the effect of levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2 studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95% CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All comparisons comparing other positive inotropic, inodilative or vasodilative drugs presented uncertainty on their effect on short-term mortality with very low-quality evidence and based on only one RCT. These single studies compared epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30 participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30 participants), dopexamine with dopamine (no in-hospital deaths from 70 participants), enoximone with dobutamine (two deaths from 40 participants) and nitric oxide with placebo (one death from three participants). AUTHORS' CONCLUSIONS: Apart from low quality of evidence data suggesting a short-term mortality benefit of levosimendan compared with dobutamine, at present there are no robust and convincing data to support a distinct inotropic or vasodilator drug-based therapy as a superior solution to reduce mortality in haemodynamically unstable people with cardiogenic shock or LCOS.Considering the limited evidence derived from the present data due to a generally high risk of bias and imprecision, it should be emphasised that there remains a great need for large, well-designed randomised trials on this topic to close the gap between daily practice in critical care medicine and the available evidence. It seems to be useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock and LCOS with early haemodynamic stabilisation within predefined timelines. Future clinical trials should therefore investigate whether such a therapeutic concept would influence survival rates much more than looking for the 'best' drug for haemodynamic support.
Asunto(s)
Gasto Cardíaco Bajo/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Infarto del Miocardio/complicaciones , Choque Cardiogénico/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Anciano , Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/mortalidad , Causas de Muerte , Dobutamina/uso terapéutico , Enoximona/uso terapéutico , Humanos , Hidrazonas/uso terapéutico , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Óxido Nítrico/uso terapéutico , Piridazinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Choque Cardiogénico/etiología , Choque Cardiogénico/mortalidad , SimendánRESUMEN
BACKGROUND: There is consistent evidence from observational studies of an association between occupational lifting and carrying of heavy loads and the diagnosis of hip osteoarthritis. However, due to the heterogeneity of exposure estimates considered in single studies, a dose-response relationship between cumulative physical workload and hip osteoarthritis could not be determined so far. METHODS: This study aimed to analyze the dose-response relationship between cumulative physical workload and hip osteoarthritis by replacing the exposure categories of the included studies with cumulative exposure values of an external reference population. Our meta-regression analysis was based on a recently conducted systematic review (Bergmann A, Bolm-Audorff U, Krone D, Seidler A, Liebers F, Haerting J, Freiberg A, Unverzagt S, Dtsch Arztebl Int 114:581-8, 2017). The main analysis of our meta-regression comprised six case-control studies for men and five for women. The population control subjects of a German multicentre case-control study (Seidler A, Bergmann A, Jäger M, Ellegast R, Ditchen D, Elsner G, Grifka J, Haerting J, Hofmann F, Linhardt O, Luttmann A, Michaelis M, Petereit-Haack G, Schumann B, Bolm-Audorff U, BMC Musculoskelet Disord 10:48, 2009) served as the reference population. Based on the sex-specific cumulative exposure percentiles of the reference population, we assigned exposure values to each category of the included studies using three different cumulative exposure parameters. To estimate the doubling dose (the amount of physical workload to double the risk of hip osteoarthritis) on the basis of all available case-control-studies, meta-regression analyses were conducted based on the linear association between exposure values of the reference population and the logarithm of reported odds ratios (ORs) from the included studies. RESULTS: In men, the risk to develop hip osteoarthritis was increased by an OR of 1.98 (95% CI 1.20-3.29) per 10,000 tons of weights ≥20 kg handled, 2.08 (95% CI 1.22-3.53) per 10,000 tons handled > 10 times per day and 8.64 (95% CI 1.87-39.91) per 106 operations. These estimations result in doubling dosages of 10,100 tons of weights ≥20 kg handled, 9500 tons ≥20 kg handled > 10 times per day and 321,400 operations of weights ≥20 kg. There was no linear association between manual handling of weights at work and risk to develop hip osteoarthritis in women. CONCLUSIONS: Under specific conditions, the application of an external reference population allows for the derivation of a dose-response relationship despite high exposure heterogeneities in the pooled studies.
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Elevación/efectos adversos , Enfermedades Profesionales/epidemiología , Osteoartritis de la Cadera/epidemiología , Vigilancia de la Población , Carga de Trabajo , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/métodos , Enfermedades Profesionales/diagnóstico , Osteoartritis de la Cadera/diagnóstico , Vigilancia de la Población/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients.In November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients. OBJECTIVES: To assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit. SEARCH METHODS: We searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC. DATA COLLECTION AND ANALYSIS: We collected and analyzed studies according to the published protocol. Summary statistics for the primary endpoints were risk ratios (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We rated the quality of evidence using GRADE methodology and summarized the quality and magnitude of relative and absolute effects for each primary outcome in our 'Summary of findings' tables. MAIN RESULTS: We identified eight studies with 4732 eligible participants and an additional 13 ongoing studies. We categorized studies into comparisons, all against standard therapy accordingly as first-line (five comparisons) or second-line therapy (one comparison) for mRCC.Interferon (IFN)-α monotherapy probably increases one-year overall mortality compared to standard targeted therapies with temsirolimus or sunitinib (RR 1.30, 95% CI 1.13 to 1.51; 2 studies; 1166 participants; moderate-quality evidence), may lead to similar quality of life (QoL) (e.g. MD -5.58 points, 95% CI -7.25 to -3.91 for Functional Assessment of Cancer - General (FACT-G); 1 study; 730 participants; low-quality evidence) and may slightly increase the incidence of adverse events (AEs) grade 3 or greater (RR 1.17, 95% CI 1.03 to 1.32; 1 study; 408 participants; low-quality evidence).There is probably no difference between IFN-α plus temsirolimus and temsirolimus alone for one-year overall mortality (RR 1.13, 95% CI 0.95 to 1.34; 1 study; 419 participants; moderate-quality evidence), but the incidence of AEs of 3 or greater may be increased (RR 1.30, 95% CI 1.17 to 1.45; 1 study; 416 participants; low-quality evidence). There was no information on QoL.IFN-α alone may slightly increase one-year overall mortality compared to IFN-α plus bevacizumab (RR 1.17, 95% CI 1.00 to 1.36; 2 studies; 1381 participants; low-quality evidence). This effect is probably accompanied by a lower incidence of AEs of grade 3 or greater (RR 0.77, 95% CI 0.71 to 0.84; 2 studies; 1350 participants; moderate-quality evidence). QoL could not be evaluated due to insufficient data.Treatment with IFN-α plus bevacizumab or standard targeted therapy (sunitinib) may lead to similar one-year overall mortality (RR 0.37, 95% CI 0.13 to 1.08; 1 study; 83 participants; low-quality evidence) and AEs of grade 3 or greater (RR 1.18, 95% CI 0.85 to 1.62; 1 study; 82 participants; low-quality evidence). QoL could not be evaluated due to insufficient data.Treatment with vaccines (e.g. MVA-5T4 or IMA901) or standard therapy may lead to similar one-year overall mortality (RR 1.10, 95% CI 0.91 to 1.32; low-quality evidence) and AEs of grade 3 or greater (RR 1.16, 95% CI 0.97 to 1.39; 2 studies; 1065 participants; low-quality evidence). QoL could not be evaluated due to insufficient data.In previously treated patients, targeted immunotherapy (nivolumab) probably reduces one-year overall mortality compared to standard targeted therapy with everolimus (RR 0.70, 95% CI 0.56 to 0.87; 1 study; 821 participants; moderate-quality evidence), probably improves QoL (e.g. RR 1.51, 95% CI 1.28 to 1.78 for clinically relevant improvement of the FACT-Kidney Symptom Index Disease Related Symptoms (FKSI-DRS); 1 study, 704 participants; moderate-quality evidence) and probably reduces the incidence of AEs grade 3 or greater (RR 0.51, 95% CI 0.40 to 0.65; 1 study; 803 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: Evidence of moderate quality demonstrates that IFN-α monotherapy increases mortality compared to standard targeted therapies alone, whereas there is no difference if IFN is combined with standard targeted therapies. Evidence of low quality demonstrates that QoL is worse with IFN alone and that severe AEs are increased with IFN alone or in combination. There is low-quality evidence that IFN-α alone increases mortality but moderate-quality evidence on decreased AEs compared to IFN-α plus bevacizumab. Low-quality evidence shows no difference for IFN-α plus bevacizumab compared to sunitinib with respect to mortality and severe AEs. Low-quality evidence demonstrates no difference of vaccine treatment compared to standard targeted therapies in mortality and AEs, whereas there is moderate-quality evidence that targeted immunotherapies reduce mortality and AEs and improve QoL.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/terapia , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Neoplasias Renales/terapia , Antineoplásicos/efectos adversos , Bevacizumab/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Ensayos Clínicos Fase III como Asunto , Humanos , Factores Inmunológicos/efectos adversos , Inmunoterapia/efectos adversos , Indoles/uso terapéutico , Interferón-alfa/uso terapéutico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Longevidad/efectos de los fármacos , Pirroles/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , SunitinibRESUMEN
BACKGROUND: Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. OBJECTIVES: To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). SELECTION CRITERIA: We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. MAIN RESULTS: We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is partly counterbalanced by increased toxicity. The benefit of epirubicin in three-drug combinations, in which cisplatin is replaced by oxaliplatin and 5-FU is replaced by capecitabine is unknown.Irinotecan extends OS slightly (by an additional 1.6 months) versus non-irinotecan-containing regimens (HR 0.87, 95% CI 0.80 to 0.95, 2135 participants, 10 studies, high-quality evidence).Docetaxel extends OS slightly (just over one month) compared to non-docetaxel-containing regimens (HR 0.86, 95% CI 0.78 to 0.95, 2001 participants, eight studies, high-quality evidence). However, due to subgroup analyses, we are uncertain whether docetaxel-containing combinations (docetaxel added to a single-agent or two-drug combination) extends OS due to moderate-quality evidence (HR 0.80, 95% CI 0.71 to 0.91, 1466 participants, four studies, moderate-quality evidence). When another chemotherapy was replaced by docetaxel, there is probably little or no difference in OS (HR 1.05; 0.87 to 1.27, 479 participants, three studies, moderate-quality evidence). We found there is probably little or no difference in OS when comparing capecitabine versus 5-FU-containing regimens (HR 0.94, 95% CI 0.79 to 1.11, 732 participants, five studies, moderate-quality evidence) .Oxaliplatin may extend (by less than one month) OS versus cisplatin-containing regimens (HR 0.81, 95% CI 0.67 to 0.98, 1105 participants, five studies, low-quality evidence). We are uncertain whether taxane-platinum combinations with (versus without) fluoropyrimidines extend OS due to very low-quality evidence (HR 0.86, 95% CI 0.71 to 1.06, 482 participants, three studies, very low-quality evidence). S-1 regimens improve OS slightly (by less than an additional month) versus 5-FU-containing regimens (HR 0.91, 95% CI 0.83 to 1.00, 1793 participants, four studies, high-quality evidence), however since S-1 is used in different doses and schedules between Asian and non-Asian population, the applicability of this finding to individual populations is uncertain. AUTHORS' CONCLUSIONS: Chemotherapy improves survival (by an additional 6.7 months) in comparison to BSC, and combination chemotherapy improves survival (by an additional month) compared to single-agent 5-FU. Testing all patients for HER-2 status may help to identify patients with HER-2-positive tumours, for whom, in the absence of contraindications, trastuzumab in combination with capecitabine or 5-FU in combination with cisplatin has been shown to be beneficial. For HER-2 negative people, all different two-and three-drug combinations including irinotecan, docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for advanced gastric cancer, and consideration of the side effects of each regimen is essential in the treatment decision. Irinotecan-containing combinations and docetaxel-containing combinations (in which docetaxel was added to a single-agent or two-drug (platinum/5-FUcombination) show significant survival benefits in the comparisons studied above. Furthermore, docetaxel-containing three-drug regimens have increased response rates, but the advantages of the docetaxel-containing three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity. Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as compared to the same regimen containing cisplatin, and there is a modest survival improvement of S-1 compared to 5-FU-containing regimens.Whether the survival benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as compared to the same regimen without epirubicin is still valid when second-line therapy is routinely administered and when cisplatin is replaced by oxaliplatin and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the observed survival benefits for the three-drug regimens is not large enough to be clinically meaningful as defined recently by the American Society for Clinical Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit was observed by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Antraciclinas/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Docetaxel , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/mortalidad , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND: Transseptal puncture for left heart interventions became a routine procedure guided by fluoroscopy and echocardiography. The use of intracardiac potentials derived from the sheath-transseptal-needle/guidewire-combination may provide helpful information to increase safety of this procedure. METHODS AND RESULTS: We recorded the intracardiac potentials from the sheath-transseptal-needle/guidewire-combination during the transseptal puncture procedure in 31 consecutive patients (mean age 67.2±8.2years; 21 in sinus rhythm, 10 in atrial fibrillation) designated for ablation of atrial fibrillation by the Cryo-balloon ® technique (Medtronic, Minnesota, USA). The EP-Navigator ® 3-D-image integration tool (Philips Healthcare, Hamburg, Germany) was used for visualization of the device position in relation to the cardiac structures. Typical and reproducible potentials could be derived in all patients for the different device localizations at transseptal puncture procedure. Especially the transition from the muscular interatrial septum into the fossa ovalis could be easily depicted by the changes of both morphology and magnitude of the atrial signal (6.1±2.3mV in sinus rhythm [SR]/3.5±0.9mV in atrial fibrillation [AF] at the muscular interatrial septum and 0.5±0.2mV in SR/0.5±0.1mV in AF in the fossa ovalis). CONCLUSIONS: The crucial steps of a transseptal procedure can be verified by typical changes (morphology and amplitude) of the intracardiac signals derived from the sheath-transseptal-needle/guidewire-combination in patients with sinus rhythm as well as in atrial fibrillation.
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Mapeo del Potencial de Superficie Corporal/métodos , Cateterismo Cardíaco/métodos , Electrodos , Tabiques Cardíacos/cirugía , Agujas , Punciones/métodos , Cirugía Asistida por Computador/métodos , Mapeo del Potencial de Superficie Corporal/instrumentación , Cateterismo Cardíaco/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Punciones/instrumentación , Cirugía Asistida por Computador/instrumentaciónRESUMEN
Tumor-stroma interactions play an essential role in the biology of colorectal carcinoma (CRC). Multipotent mesenchymal stromal cells (MSC) may represent a pivotal part of the stroma in CRC, but little is known about the specific interaction of MSC with CRC cells derived from tumors with different mutational background. In previous studies we observed that MSC promote the xenograft growth of the CRC cell-line DLD1. In the present study, we aimed to analyze the mechanisms of MSC-promoted tumor growth using various in vitro and in vivo experimental models and CRC cells of different mutational status. MSC specifically interacted with distinct CRC cells and supported tumor seeding in xenografts. The MSC-CRC interaction facilitated three-dimensional spheroid formation in CRC cells with dysfunctional E-cadherin system. Stable knock-downs revealed that the MSC-facilitated spheroid formation depended on ß1-integrin in CRC cells. Specifically in α-catenin-deficient CRC cells this ß1-integrin-dependent interaction resulted in a MSC-mediated promotion of early tumor growth in vivo. Collagen I and other extracellular matrix compounds were pivotal for the functional MSC-CRC interaction. In conclusion, our data demonstrate a differential interaction of MSC with CRC cells of different mutational background. Our study is the first to show that MSC specifically compared to normal fibroblasts impact early xenograft growth of distinct α-catenin deficient CRC cells possibly through secretion of extracellular matrix. This mechanism could serve as a future target for therapy and metastasis prevention.
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Neoplasias Colorrectales/patología , Integrina beta1/metabolismo , Células Madre Mesenquimatosas , Microambiente Tumoral/fisiología , Animales , Western Blotting , Línea Celular Tumoral , Técnicas de Cocultivo , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Desnudos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVES: The objective of this systematic review was to summarize the evidence of calcium and magnesium (CaMg) infusions in the prevention of oxaliplatin-induced neuropathy on the basis of prospective randomized controlled trials (RCTs). METHODS: A systematic search included MEDLINE and CENTRAL, plus major oncology conferences, and identified RCTs evaluating CaMg. Efficacy endpoints were chronic neurotoxicity measured with National Cancer Institute Common Terminology Criteria for Adverse Events grades and the oxaliplatin-specific scale (OSS). Data were synthesized using a random effects model. RESULTS: A total of 5 trials with 694 evaluable patients were included in this analysis. The pooled result stated the outcome of the largest study included [Loprinzi et al.: J Clin Oncol 2014;32:997-1005], in which no differences were detected for the incidence of grade ≥2 neuropathy between those receiving CaMg infusions and controls [relative risk (RR) 0.81, 95% confidence interval (CI) 0.60-1.11]. Only 2 studies (n = 52) quoted an incidence of chronic neurotoxicity for all grades (with a pooled RR of 0.95 and 95% CI 0.69-1.32), with substantial statistical heterogeneity. Three studies reported an actual incidence of the OSS but, due to the detected substantial statistical heterogeneity, the studies were not pooled. CONCLUSION: The results of our systematic review demonstrated the nonbeneficial effect of CaMg infusions for the prevention of oxaliplatin-induced peripheral neuropathy.