Spatial health risk assessments of nickel in the groundwater sources of a mining-impacted area.

Mining activities have increased the potential risks of metal pollution to the groundwater resources in arid areas across the globe. Therefore, this study aimed to examine the health risk associated with nickel (Ni) in the groundwater sources of a mining-impacted area, South Khorasan, Eastern Iran. A total of 110 stations were included in the study, comprising 62 wells, 40 qanats, and 8 springs in summer, 2020. Initially, the collected samples were tested for temperature, pH, and electrical conductivity (EC). Subsequently, the samples were filtered and treated with nitric acid (HNO3) to measure the concentration of Ni using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Hazard quotient (HQ) and non-carcinogenic risk assessments were employed to evaluate the potential risks of Ni to the inhabitants. The findings revealed that the concentration of Ni ranged from 0.02 to 132.39 µg l-1, and only two stations exhibited Ni concentrations above the WHO standards (20 µg l-1). The results demonstrated that 98.21% of the sampled locations had HQ values below one, indicating negligible risk, while 1.78% of the stations exhibited HQ values of one or higher, representing a high non-carcinogenic risk for water consumers. Overall, the concentration of nickel in the groundwater of South Khorasan exceeded the World Health Organization (WHO) limit solely in the Halvan station, posing a non-carcinogenic risk for the residents in that area, and therefore, additional efforts should be made to provide healthier groundwater to consumers in this region.

A Systematic Review of Health Management Mobile Applications in COVID-19 Pandemic: Features, Advantages, and Disadvantages.

Introduction: With the increasing accessibility of smartphones, their use has been considered in healthcare services. Mobile applications have played a pivotal role in providing health services during COVID-19. This study is aimed at identifying the features, advantages, and disadvantages of health management mobile applications during COVID-19. Methods: This systematic review was conducted in PubMed, Scopus, and Web of Science using the related keywords up to November 2021. The original articles in English about the health management mobile applications in COVID-19 were selected. The study selection was done by two researchers independently according to inclusion and exclusion criteria. Data extraction was done using a data extraction form, and the results were summarized and reported in related tables and figures. Results: Finally, 12 articles were included based on the criteria. The benefits of mobile health applications for health management during COVID-19 were in four themes and 19 subthemes, and the most advantages of the application were in disease management and the possibility of recording information by users, digital tracking of calls, and data confidentiality. Furthermore, the disadvantages of them have been presented in two themes and 14 subthemes. The most common disadvantages are reduced adherence to daily symptom reports, personal interpretation of questions, and result bias. Conclusion: The study results showed that mobile applications have been effective in controlling the prevalence of COVID-19 by identifying virus-infested environments, identifying and monitoring infected people, controlling social distancing, and maintaining quarantine. It is suggested that usability, ethical and security considerations, protection of personal information, and privacy of users be considered in application design and development.

Pulsed sonodynamic therapy of melanoma cancer cells using nanoparticles of and mesoporous platinum.

OBJECTIVE: Noble metal nanomaterials have been introduced as ideal sonosensitizers for sonodynamic therapy (SDT) of cancer. In this research, platinum nanoparticles (PtNPs) and mesoporous platinum (MPt) were first synthesized and then evaluated as novel sonosensitizers. METHODS: Ultrasound waves were radiated at two different power densities and two different pulse ratios to develop a pulsed radiation route for SDT of the malignant melanoma cell line C540 (B16/F10). Fluorescence emission was recorded as an indicator of intracellular reactive oxygen generation during the treatment. RESULTS: Platinum nanoparticles had an average diameter of 12 ± 7 nm and a zeta potential of -17.6 mV; also, MPt had a sponge-like and highly porous structure with a pore size <11 nm and a zeta potential of -39.5 mV. Both PtNPs and MPt, particularly the latter, enhanced the rate of inhibition of tumor cell growth on ultrasound radiation at an output power density of 1.0 W cm-2 and pulse ratio of 30% over 10 min without intensifying temperature. CONCLUSION: Use of the developed pulsed (rather than continuous) radiation in SDT and PtNPs or MPT, without hyperthermia, resulted in a new effective cancer treatment method based on the mechanisms of cavitation and/or ROS generation.

A bibliometric analysis of scientific research trends in monitoring systems for measuring ship emissions.

The maritime sector plays a key role in transportation in the world, and over 90% of world trade is carried by ocean shipping. However, ships are large contributors to global emissions. Hence, a vast majority of research publications have focused on different emission monitoring techniques, which are essential to establishing required policies and regulations that reduce maritime transport emissions. Various documents have been published on monitoring maritime transport emissions affecting air quality since 1977. This paper presents a bibliometric analysis to explore evolution trends, gaps, challenges, and productive countries, as well as the most cited publications with high scholarly impacts. The annual growth of 9.64% in publications demonstrates an increasing interest in reducing maritime vessel emissions. Journal articles constitute 69% of publications, followed by conference papers (25%). China and the USA play a leading role in this field of research. Regarding active resources, the "Atmospheric Environment" journal accounts for the highest relevant publications, H-index, and total citations. Eventually, the temporal evolution of keywords shows the increasing trend towards sustainable maritime transport.

Fractionated Sonodynamic Therapy Using Gold@Poly(ortho-aminophenol) Nanoparticles and Multistep Low-Intensity Ultrasound Irradiation to Treat Melanoma Cancer: In Vitro and In Vivo Studies.

OBJECTIVE: Cancer treatment using ultrasound irradiation with low intensities along with a sonosensitizer has been found to have significant advantages, such as high penetration depth in tissues, non-invasive therapeutic character, minor side effects, good patient adherence and preferential tumor area treatment. In the present study, gold nanoparticles covered by poly(ortho-aminophenol) (Au@POAP NPs) were synthesized and characterized as a new sonosensitizer. METHODS: We investigated Au@POAP NPs efficacy on fractionated ultrasound irradiation for treatment of melanoma cancer in vitro as well as in vivo. DISCUSSION: In vitro examinations revealed that although Au@POAP NPs (with a mean size of 9.8 nm) alone represented concentration-dependent cytotoxicity against the B16/F10 cell line, multistep ultrasound irradiation (1 MHz frequency, 1.0 W/cm2 intensity, 60 s irradiation time) of the cells in the attendance of Au@POAP NPs led to efficient cell sonodynamic therapy (SDT) and death. Histological analyses revealed that in vivo fractionated SDT toward melanoma tumors of male balb/c mice led to no residual viable tumor cell after 10 d. CONCLUSION: A deep sonosensitizing effectiveness of Au@POAP NPs on fractionated low-intensity ultrasound irradiation was attained with the main mechanism of tumor cell eradication of promotion of apoptosis or necrosis through dramatically increased reactive oxygen species levels.

Management of Cancer Patients in the COVID-19 Crisis Using Telemedicine: A Systematic Review.

BACKGROUND: Telemedicine can provide a solution for disease management during the COVID-19 pandemic. This literature review aims to explore the role of telemedicine during the COVID-19 pandemic for management of cancer patients. METHOD: A comprehensive systematic search was conducted in PubMed, Science Direct, EMBASE, and Web of Science databases for the papers published until April 2021. Studies were included in case they had practically used telemedicine in the management of cancer patients during the COVID-19 crisis. RESULTS: After screening 2614 titles and abstracts and reviewing 305 full-texts, 16 studies were found to be eligible. The results indicated that most of the patients contacted by telemedicine services mostly used to intract with patients breast cancer (n=4, 25%). The most common use of telemedicine was the provision of virtual visit services (n=10, 62.25%). Besides, communication was most frequently provided by live video conferences (n=11, 68.75%). CONCLUSION: Telemedicine can provide continued access to necessary health services in oncology care and serve as an important role in pandemic planning and response.

Helicobacter pylori infection in pediatrics with gastrointestinal complaints.

BACKGROUND: Helicobacter pylori is one of the most important pathogenic bacteria in gastric mucosa both in adults and pediatrics. Here we aimed to investigate the prevalence of Helicobacter pylori in pediatrics with gastrointestinal complaints by the endoscopic method and using pathology reports. METHODS: This is a cross-sectional study that was performed in 2019-2020 in Imam Hossein hospital affiliated to Isfahan University of Medical Sciences on medical documents of pediatrics that underwent gastric or duodenal biopsy via endoscopy. We collected data regarding patients' age, gender, place of residence, type of gastrointestinal complaints, and prevalence of Helicobacter pylori infection from the medical reports. We also investigated the possible correlation between the presence of Helicobacter pylori and the type of complaints among patients. RESULTS: A total number of 400 pediatrics entered the study. Abdominal pain was the most common complaint (42%). Helicobacter pylori infection was found in 31 cases (7.8%). The prevalence of Helicobacter pylori infection in boys (10.7%) was significantly higher than in girls (4.6%) (P = 0.02) and was significantly related to the age group of children (P<0.001) in the way that Helicobacter pylori infection was more common in higher ages. There was no significant relationship between the prevalence of Helicobacter pylori infection and the type of complaint (P = 0.29). CONCLUSION: We showed that the prevalence of Helicobacter pylori infection is low among pediatrics with gastrointestinal complaints and this issue could cast doubt on the high prevalence rates and importance of this infection in children.

Estimating brain effective connectivity from EEG signals of patients with autism disorder and healthy individuals by reducing volume conduction effect.

Studying brain connectivity has shed light on understanding brain functions. Electroencephalogram signals recorded from the scalp surface comprise inter-dependent multi-channel signals each of which is a linear combination of simultaneously active brain sources as well as adjacent non-brain sources whose activity is widely volume conducted to the scalp through overlapping patterns. Evaluation of brain connectivity based on multivariate autoregressive (MVAR) model identification from neurological time series can be a proper tool for brain signal analysis. However, the MVAR model only considers the lagged influences between time series while ignoring the instantaneous effects (zero-lagged interactions) among simultaneously recorded neurological signals. Hence predicting instant interactions may result in fake connectivity, which may lead to misinterpreting in results. In this study, we aim to find instantaneous effects from coefficients of the MVAR model acquired using an ADALINE neural network and investigate the efficiency of the proposed algorithm by applying it to a simulated signal. We show that our coefficients are estimated accurately from channels of the simulated signal. Moreover, we apply the proposed method on a dataset of a group of 18 healthy children and 10 children with autism by comparing their effective connectivity estimated by direct directed transfer function method using new and old coefficients. Finally, to show the efficiency of the algorithm we exploit the support vector machine method for classifying the dataset. We show that there is a significant improvement in the results obtained from the proposed method.

Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Since numerous studies have stated that there may be a relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease, and because of the high prevalence of both conditions worldwide, this study investigated the risk of non-alcoholic fatty liver disease in patients infected with H. pylori. Following a systematic review of PubMed, Scopus, Web of Science and Embase, and a search in Google Scholar using MeSH terms such as H. pylori and non-alcoholic fatty liver disease, the relevant papers up to November 2020 were reviewed. All cohort, case-control, and cross-sectional studies that examined the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori entered this study. A meta-analysis was conducted in STATA 11. This systematic review examined 22 papers with 117 117 participants (33 711 patients infected with H. pylori and 83 406 participants as control) and 20 studies were subjected to meta-analysis The results indicated a 22% to 27% increase in the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori (crude odds ratio: 1.27, 95% CI: 1.17-1.33; and adjusted odds ratio: 1.22, 95% CI: 1.09-1.35). According to the subgroup analysis, the study region, sample size, and the method of diagnosing H. pylori were the factors contributing to the high heterogeneity. The meta-analysis revealed the increased risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori. This indicates that H. pylori is a serious risk factor in patients susceptible to NAFLD.

Prerequisites of Personal Health Record for Chronic Kidney Disease: A Scoping Review and Evaluation of the Content Validity.

BACKGROUND: It is obvious that the Personal Health Record (PHR) is a major cornerstone for "improving the self-management of patient". However, lack of an effective and comprehensive personal health record system prohibits the widespread use of PHRs. The aim of this study was to identify the core data sets and required functionalities for designing a PHRs for chronic kidney disease (CKD) management and assess their validity. METHODS: It was a study including two phases. In the initial phase, a scoping review was conducted with the aim of determination the core data sets and required functionalities for designing PHRs. Then in the second phase, the validity of data items and functionalities was determined by 25 multidisciplinary experts. RESULTS: 22 studies were eligible after screening 1335 titles and abstracts and reviewing 88 full texts. We determined 20 core data set and 8 required functionalities of PHRs. From the perspective of experts, 'health maintenance' and 'advance directives' were most often marked as useful but not essential, while 'test and examination', 'medication list' and 'diagnosis and comorbid conditions" were predominantly considered as essential by all experts (n=25,100%). CONCLUSION: This research is a step that we have taken to identify prerequisites that could be used for the design, development, and implementation of an effective and comprehensive electronic personal health record.

International classification of external causes of injury: a study on its content coverage.

BACKGROUND: Injuries are a major health issue worldwide and their prevention requires access to accurate statistics in this regard. This can be achieved by classifying the collected data using the international classification systems. This study aimed at investigating the content coverage rate of the International Classification of External Causes of Injury (ICECI) regarding the external causes of injury in a hospital. METHODS: This cross-sectional descriptive-analytical study was performed on 322 injured individuals visiting the emergency unit of a hospital which is the biggest truma center in the southeast of Iran. The required data were collected via a designed questionnaire by the researcher visiting the Emergency ward. The collected data were encoded based on the ICECI textbook by two encoders. Their agreement rate was calculated using the Kappa estimate of agreement. The content coverage of the classification system and the degree of completeness of the required data for encoding in the patients' records were measured. Data were analyzed by the SPSS software, ver 19. RESULTS: The findings showed that 70% of the external causes of injury were covered by ICECI. Among the 322 cases, 138 (43%) had been referred due to a car crash. The injured were mostly drivers of land transport vehicles who had been unintentionally involved in a car crash. The least mechanism for injury was bite injury with 5 (2%). ICECI was capable of classifying 92% of the data related to the external causes of the injuries. The most un-covered data has belonged to the "activity when injured" axis (n = 18). Lack of precise data recording in the medical records resulted in missing data about at least one of the axis of the external causes in most records. CONCLUSION: The findings of the present study showed that ICECI has good content coverage for encoding the external causes of injuries. Before implementing ICECI for encoding the external causes of injuries, it is required to train clinicians regarding how to document all aspects of an injury incidence.

High-level Gentamicin Resistance among Clinical Isolates of Enterococci in Iran: a Systematic Review and Meta-analysis.

Enterococci have been considered as one of the most common causes of nosocomial infections. The spread of antibiotic resistance has posed a serious challenge to treating the enterococcal infections. High-level aminoglycosides resistance leads to failure in the synergistic combination therapy. This study aimed to estimate the prevalence of high-level gentamicin resistance (HLGR) among clinical isolates of enterococci in Iran.Systematic literature search was conducted in the Web of Science, PubMed, Scopus and Google Scholar electronic databases from ar-ticles which were published from April 2000 to September 2018. Literature search yielded 918 studies. Eligible studies were selected ac-cording to the defined inclusion and exclusion criteria. Statistical heterogeneity was estimated by Q statistic and the I2 index. The Begg's rank correlation test and Egger's weighted regression tests were used to evaluate possible publication bias.Nineteen studies were included in this review. According to the meta-analysis results, the prevalence of HLGR among Enterococcus spp. was 49.4% (95% CI: 42.2%-56.6%). It was estimated 44.3% (95% CI: 38.1%-50.8%) and 66.3% (95% CI: 51.4%-78.6%) for E. faecalis and E. faecium, respectively.Since notable rate of HLGR in enterococci was seen in this analysis, improving the implementation of all aspects of the infection control programmes is required. Accurate and regular monitoring of infection control procedures are necessary for reducing the dissemination of such infections.

Reliability of multi-purpose offshore-facilities: Present status and future direction in Australia.

Sustainable use of the ocean for food and energy production is an emerging area of research in different countries around the world. This goal is pursued by the Australian aquaculture, offshore engineering and renewable energy industries, research organisations and the government through the "Blue Economy Cooperative Research Centre". To address the challenges of offshore food and energy production, leveraging the benefits of co-location, vertical integration, infrastructure and shared services, will be enabled through the development of novel Multi-Purpose Offshore-Platforms (MPOP). The structural integrity of the designed systems when being deployed in the harsh offshore environment is one of the main challenges in developing the MPOPs. Employing structural reliability analysis methods for assessing the structural safety of the novel aquaculture-MPOPs comes with different limitations. This review aims at shedding light on these limitations and discusses the current status and future directions for structural reliability analysis of a novel aquaculture-MPOP considering Australia's unique environment. To achieve this aim, challenges which exist at different stages of reliability assessment, from data collection and uncertainty quantification to load and structural modelling and reliability analysis implementation, are discussed. Furthermore, several solutions to these challenges are proposed based on the existing knowledge in other sectors, and particularly from the offshore oil and gas industry. Based on the identified gaps in the review process, potential areas for future research are introduced to enable a safer and more reliable operation of the MPOPs.

Application of geographic information systems in maternal health: a scoping review.

BACKGROUND: Improving maternal health is a global health priority and requires accurate evaluation of factors affecting maternal health. Geographic information systems have been used to explore maternal health problems. AIMS: The aim of this study was to identify studies that used geographic information systems in the field of maternal health care and to determine maternal health and mortality variables visualized on these systems. METHODS: This was a scoping review in which we systematically searched PubMed and Science Direct for studies that used geographic information systems to evaluate maternal health care. We included all relevant cross-sectional studies published in English between December 1995 and December 2017. We extracted the following information from each study included: study year, region, objectives, type of geographic information system used, variables visualized by the geographic information system, and all other variables examined that related to maternal health. RESULTS: Of 5240 articles initially retrieved, 40 were included for detailed review. Most of the studies (n = 32) were done in developing countries in Africa, Asia, and Latin America and the Caribbean. Most of the studies (n = 33) visualized mothers' distance to health facilities and travel time to health care centres on geographic information systems. Other factors examined included antenatal care capacity (n = 4) and capacity of maternal health services (n = 3). CONCLUSIONS: Comprehensive research on the application of geographic information systems in maternal care is lacking. Most studies applied simple descriptive mapping of spatial distribution patterns with a few relevant variables.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.

OBJECTIVE: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. METHODS: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. CONCLUSIONS: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Assessment of changes in physiological and biochemical traits in four pistachio rootstocks under drought, salinity and drought + salinity stresses.

In this study, 7-month-old UCB-1, Badami, Ghazvini and Kale-Ghouchi pistachio rootstocks were exposed to control, drought, salinity and drought + salinity environments for 60 d. Total chlorophyll and total carotenoid contents decreased in all cultivars under drought, salinity and drought + salinity stresses. Under drought and salinity stresses, alone or in combination, Na+ and Cl- ions increased in all four pistachio rootstocks, while K+ ion decreased only in Ghazvini and Kaleh-Ghouchi cultivars. The enzyme activities of ascorbate peroxidase, polyphenol oxidase, catalase and guaiacol peroxidase increased in all cultivars when subjected to all three stresses with the exception of the ascorbate peroxidase activity in Kale-Ghouchi cultivar during drought stress. Oxidative stress parameters including electrolyte leakage, malondialdehyde, other aldehydes and hydrogen peroxide increased under all three stress conditions in all genotypes. The content of proline, total free amino acids and total soluble carbohydrates were enhanced under drought, salinity and drought + salinity stresses, whereas the protein content decreased in all pistachio rootstocks. In all evaluated traits, except for the K+ ion content and APX activity, the highest impacts was seen for drought + salinity > salinity > drought stresses, respectively. For the first time, we have proven that K+ ion content has a positive correlation with the ascorbate peroxidase, polyphenol oxidase, catalase and guaiacol peroxidase enzymes activities under drought + salinity stress. Finally, based on the bi-plot and cluster analyses, we have selected the UCB-1 > Badami > Ghazvini > Kale-Ghouchi cultivars as the most tolerant pistachio rootstocks under drought + salinity stress, respectively.

Assessment of changes in growth traits, oxidative stress parameters, and enzymatic and non-enzymatic antioxidant defense mechanisms in Lepidium draba plant under osmotic stress induced by polyethylene glycol.

Lepidium draba is a weed with the medicinal properties which few researches have been done on it. In this study, some traits, related to the osmotic stress, in 14-day-old L. draba sprouts that were grown 9 days in the presence of various doses of polyethylene glycol 6000 (PEG 6000) including 0, 3, 6, 9, and 12%, with different osmotic potentials (- 0.04, - 0.12, - 0.23, - 0.34, and - 0.48 MPa, respectively) were investigated. Based on our results, germination percentage besides stem and root lengths decreased with increasing the concentrations of PEG. The contents of electrolyte leakage, malondialdehyde, other aldehydes, total protein, free amino acids, total soluble carbohydrate as well as free proline increased with increasing the concentrations of PEG. Also, for the first time, our results have proven that under osmotic stress, there is an adverse relationship between hydrogen peroxide content and the activity of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase enzymes, such that hydrogen peroxide content decreased with induction of PEG up to 6% and after that increased, while the activity of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase enzymes increased up to 6% PEG and after that decreased. The expression levels of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase genes showed the same pattern as was seen for these enzyme activities. According to the results of this study, it can be deduced that decreasing H2O2 content cannot be the main reason for other oxidative stress parameters to decrease. In this study, P5CS and P5CR gene expression levels increased with increasing levels of PEG up to 12% which was completely similar to free proline content. Based on our results, L. draba can be considered as a semi-tolerant plant to osmotic stress.

Critical Appraisal of Mental Health Applications.

BACKGROUND: Using mobile applications in health is progressing rapidly; hence, assessing them is essential to ensure their quality and standards. The present study was designed to critically evaluate the quality of existing applications in the field of mental health. METHODS: In this is review the related keywords "Health and Mental health" were used in Persian and English to search in 4 application platforms: App Store, Google Play, Bazar (Persian version of Google Play), Sib app (Persian version of App Store). Inclusion criteria for the applications were either in Persian or English language and compatible with Android or IOS. The exclusion criteria were any application downloaded less than 100 times and those that were one dimensional such as only focusing on sleep disorder. A team of researchers reviewed each app in terms of two sets of criteria: 1) Mobile App Rating Scale (MARS) subdomain scores for reviewing engagement, functionality, esthetics, and information; and 2) personalization level. RESULT: The search resulted in 958 apps, of which 61 had the inclusion criteria. Most of them (n=59, 97%) were rated as appropriate for all age groups and only two were designed for children. In MARS score, thirty-three percent (n=5) of the Persian apps received the rating of 2.5 or higher, while this score was 53 percent (n=27) for English applications. Eight application (13%) used dialogue boxes for personalization and 11 (18%) had feedback capability. None of the Persian apps could be personalized. CONCLUSION: Although numerous apps are available, there are only few apps with personalization features, which should be considered as one of the key features when developing this type of apps.

West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer.

PURPOSE: The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC). PATIENTS AND METHODS: Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E)90/cyclophoshamide (C)600 followed by four cycles of docetaxel (T)100 or six cycles of T75C600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined. RESULTS: Of the 3,198 registered patients, 348 (RS ≤ 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v 60.8%; pN0, 58.2% v 59.5%; pT1, 57.6% v 52.3%; HR positive, 81.4% v 82.2%; RS greater than 25 [in HR-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v 89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v 94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status. CONCLUSION: In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2-negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease.

Correction to: Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial.

The article Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial, written by Ulrike Nitz, Oleg Gluz, Matthias Christgen, Ronald E. Kates, Michael Clemens, Wolfram Malter, Benno Nuding, Bahriye Aktas, Sherko Kuemmel, Toralf Reimer, Andrea Stefek, Fatemeh Lorenz-Salehi, Petra Krabisch, Marianne Just, Doris Augustin, Cornelia Liedtke, Calvin Chao, Steven Shak, Rachel Wuerstlein, Hans H. Kreipe, Nadia Harbeck, was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 29, 2017 without open access.With the author(s)' decision to opt for Open Choice the copyright of the article changed on January 6, 2019 to © The Author(s) 2017 and the article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license and any changes made are indicated. The original article has been corrected.