A Breast Cancer Outcomes model was developed at the ONCOTYROL research center to evaluate personalized test-treatment strategies in Austria. The goal was to evaluate the cost-effectiveness of a new 21-gene assay (ODX) when used in conjunction with the Adjuvant! Online (AO) decision aid to support personalized decisions about use of adjuvant chemotherapy in early-stage breast cancer patients in Austria. We applied a validated discrete-event-simulation model to a hypothetical cohort of 50 years old women over a lifetime horizon. The test-treatment strategies of interest were defined using three-letter acronyms. The first (second, third) letter indicates whether patients with a low (intermediate, high) risk according to AO were tested using ODX (Y yes, N no). The main outcomes were life-years gained, quality-adjusted life-years (QALYs), costs and cost effectiveness. Robustness of the results was tested in sensitivity analyses. Results were compared to a Canadian analysis conducted by the Toronto Health Economics and Technology Assessment Collaborative (THETA). Five of eight strategies were dominated (i.e., more costly and less effective: NNY, NYN, YNN, YNY, YYN). The base-case analysis shows that YYY (ODX provided to all patients) is the most effective strategy and is cost effective with an incremental cost-effectiveness ratio of 15,700 EUR per QALY gained. These results are sensitive to changes in the probabilities of distant recurrence, age and costs of chemotherapy. The results of the base-case analysis were comparable to the THETA results. Based on our analyses, using ODX in addition to AO is effective and cost effective in all women in Austria. The development of future genetic tests may require alternative or additional test-treatment strategies to be evaluated.
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Δευτέρα 30 Νοεμβρίου 2015
Cost effectiveness of personalized treatment in women with early breast cancer: the application of OncotypeDX and Adjuvant! Online to guide adjuvant chemotherapy in Austria
Symptomatic small schwannoma is a risk factor for surgical complications and correlates with difficulty of enucleation
Postoperative neurological deficits of schwannomas are the complications that we want to avoid most. Predicting postoperative neurological deficits is crucial; however, the correlation between preoperative symptoms and neurological findings with postoperative neurological complications has not yet been completely clarified. Here we analyzed the risk factors for postoperative neurological complications. The study included 131 tumors from 107 patients histologically confirmed as schwannomas, which developed in the extremities and trunk without spinal cord involvement. The correlation between clinical findings and postoperative complications were statistically analyzed. One-hundred three tumors (78.6 %) had the preoperative neurological symptoms; these symptoms were detected in 93.3 % of small tumors (<4 cm 3 ). We defined it as follows about the anatomical location of schwannomas. One is "central type" that normal nerve bundles widely splayed over the tumor's capsule (tumor located in the central region of the nerve). Another is "peripheral type" that easy to enucleate without neurolysis (tumor located in the peripheral region of the nerve). Static analysis showed a significant difference in the Tinel sign, numbness, and postoperative neurological deficits (p = 0.04, 0.006, p < 0.001, respectively). Twenty-one cases (16.0 %) showed new postoperative neurological symptoms, including numbness in 12 cases, dysesthesia in three cases, pain in three cases, and slight motor palsy in two cases. In statistical analysis, small tumors (<4 cm 3 ) significantly correlated with Tinel sign (p < 0.001), and was marginally significant with postoperative neurological deficits (p = 0.05). Moreover, small tumors (<4 cm 3 ) accompanying numbness preoperatively significantly correlated with postoperative neurological deficits (p = 0.04). Small (<4 cm 3 ) tumors significantly correlated with the preoperative neurological symptoms. Those tumors accompanying numbness also significantly correlated with the difficulty of the enucleation and postoperative neurological deficits. These findings will help to predict the neurological complication.
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Lymphocyte subpopulations in myocardial infarction: a comparison between peripheral and intracoronary blood
The frequency and profile of lymphocyte subsets within the culprit coronary artery were investigated in 33 patients with myocardial infarction and compared to their systemic circulating counterparts. T cell subsets including CD4 + CD28null, activated and regulatory T-cells, TH1/TH2/TH17 phenotypes, NK and B-cells were studied in intracoronary (IC) and arterial peripheral blood (PB) samples. CD4 + CD28null T-lymphocytes were significantly increased in IC compared to PB (3.7 vs. 2.9 %, p < 0.0001). Moreover, patients with more than 6 h of evolution of STEMI exhibited higher levels of CD4 + CD28null T-cells suggesting that this subset may be associated with more intense myocardial damage. The rare NK subpopulation CD3 − CD16 + CD56 − was also increased in IC samples (5.6 vs. 3.9 %, p = 0.006). CD4 + CD28null T-cells and CD3 − CD16 + CD56 − NK subpopulations were also associated with higher CK levels. Additionally, IFN-γ and IL10 were significantly higher in IC CD4 + lymphocytes. Particular immune cell populations with a pro-inflammatory profile at the site of onset were increased relative to their circulating counterparts suggesting a pathophysiological role of these cells in plaque instability, thrombi and myocardial damage.
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The demographics of patients affected by surgical disease in district hospitals in two sub-Saharan African countries: a retrospective descriptive analysis
Background: There is a growing awareness of the importance of surgical disease within global health. We hypothesised that surgical disease in low income countries predominantly affects young adults and may therefore have a significant economic impact. Methods: We retrospectively reviewed all surgical admission data from two rural government district hospitals in two different sub-Saharan African countries over a 6-month period. We analysed all surgical admissions with respect to patient demographics (age and gender), diagnosis, and procedure performed. Results: Surgical admissions accounted for 12.9 and 19.8 % of all hospital admissions in Malawi and Sierra Leone respectively. 18.5 and 6.2 % of all hospital patients required a surgical procedure in Malawi and Sierra Leone respectively, with the low number in Sierra Leone accounted for in that many of the obstetric admissions were referred to a nearby Medicins Sans Frontiers (MSF) hospital for treatment. 17.9 and 10.5 % of surgical admissions were under the age of 16 in Malawi and Sierra Leone respectively, with 16–35 year olds accounting for 57.3 % of surgical admissions in Sierra Leone and 53.5 % in Malawi. Men accounted for 53.7 and 46.0 % of surgical admissions in Sierra Leone and Malawi respectively. An unexpected finding was the high level of patients who absconded from hospital in Sierra Leone after diagnosis but before treatment. This involved 11.8 % of all surgical patients, including 38 % with a bowel obstruction, 39 % with peritonitis and 20 % with ectopic pregnancy. Conclusions: Most people affected by disease requiring surgery are young adults and this may have significant economic implications.
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How welcome do Iranian-Americans feel in their homeland? Perceptions of social distance among Muslim, Jewish, and Non-Religious Iranian-American adults
Recent political events in the United States have created a political climate that promotes prejudice against Middle Eastern, Iranian, and Muslim people. In this study, we were interested in investigating two questions: (1) How welcome do Iranian-American men and women from various religious backgrounds (Muslim, Jewish, or no religious affiliation) feel in their new homeland (specifically, how much social distance (affective distance) do they think their Euro-American neighbors feel toward them? and (2) to what extent does the possession of stereotypical Middle Eastern, Iranian, or Muslim traits (an accent, darker skin, wearing of religious symbols, traditional garb, etc.) spark prejudice and thus Iranian-Americans perception of social distance? Participants were recruited from two very different sources: (1) shoppers at grocery stores in Iranian-American neighborhoods in Los Angeles, and (2) a survey posted on http://Surveymonkey.com. A total of 374 Iranian-Americans, ages 18 and older, completed an in-person or online questionnaire that included the following: a request for demographic information, religious preferences, a survey of how typically Iranian-American the respondents' traits were, and the social distance scale. A surprise was that it was the Iranian-American Jews (not the Muslims), who felt most keenly that Euro-Americans kept them at a distance. Jewish women received higher scores on the social distance scale than did members of any other group. In addition, again, it was mainly Iranian-American Jews, particularly those who spoke with a Middle Eastern accent or wore stereotypically religious symbols, who felt the most social distance existing between them and "typical" Americans.
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Multi technique amalgamation for enhanced information identification with content based image data
Image data has emerged as a resourceful foundation for information with proliferation of image capturing devices and social media. Diverse applications of images in areas including biomedicine, military, commerce, education have resulted in huge image repositories. Semantically analogous images can be fruitfully recognized by means of content based image identification. However, the success of the technique has been largely dependent on extraction of robust feature vectors from the image content. The paper has introduced three different techniques of content based feature extraction based on image binarization, image transform and morphological operator respectively. The techniques were tested with four public datasets namely, Wang Dataset, Oliva Torralba (OT Scene) Dataset, Corel Dataset and Caltech Dataset. The multi technique feature extraction process was further integrated for decision fusion of image identification to boost up the recognition rate. Classification result with the proposed technique has shown an average increase of 14.5 % in Precision compared to the existing techniques and the retrieval result with the introduced technique has shown an average increase of 6.54 % in Precision over state-of-the art techniques.
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Cloning and transcriptional expression of a novel gene during sex inversion of the rice field eel (Monopterus albus)
We performed annealing control primer (ACP)-based differential-display reverse transcription-polymerase chain reaction (DDRT-PCR) to isolate differentially expressed genes (DEGs) from the stage IV ovary and ovotestis of the rice field eel, Monopterus albus. Using 20 arbitrary ACP primers, 14 DEG expressed-sequence tags were identified and sequenced. The transcriptional expression of one DEG, G2, was significantly greater in the ovotestis than the stage IV ovary. To understand the role of G2 in sex inversion, G2 cDNA was cloned and semi-RT-PCR, real time PCR were performed during gonad development. The full-length G2 cDNA was 650 base pairs (bp) and it comprised a 5′-untranslated region (UTR) of 82 bp, a 3′-UTR of 121 bp and an open reading frame of 444 bp that encoded a 148-amino acid protein. The expression of G2 was weak during early ovarian development until the stage IV ovary, but expression increased significantly with gonad development. We speculate that G2 may play an important function during sex inversion and testis development in the rice field eel, but the full details of the function of this gene requires further research.
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On a conjecture of R. Brück and some linear differential equations
In this paper, we mainly investigate the Brück conjecture concerning entire function f and its differential polynomial L 1 ( f ) = a k ( z ) f ( k ) + ⋯ + a 0 ( z ) f sharing an entire function α ( z ) with σ ( α ) ≤ σ ( f ) , by using the theory of complex differential equation.Mathematics Subject Classification: 39B32, 30D 35.
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Three drugs vs two drugs first-line chemotherapy regimen in advanced gastric cancer patients: a retrospective analysis
The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients in the clinical practice. Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A = three drugs; group B = two drugs). A total of 425 patients were eligible for our analysis. 216 patients (50.8 %) received three chemotherapeutic agents (group A) and 209 patients (49.2 %) received a two drugs regimen as first-line combination chemotherapy (group B). RR for group A and B was 44 and 29.6 %, respectively (p = 0.0005), median PFS was 7.3 months in group A and 4.5 months in group B (p = 0.0007). No significant difference was found in terms of OS. The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, the use of a sequential approach may represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.
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The Nobel Prize 2015: The fight against parasitic diseases continues
Artemisinin and Avermectin/Ivermectin – the discoveries that were awarded this year's Nobel Prize in Medicine or Physiology – have saved millions of lives from malaria, river-blindness and elephantiasis. The fight against the diseases continues – here in Karolinska Institutet's laboratories too. A large percentage of the annual 500,000 estimated victims of malaria are babies; older children and adults in malaria-ridden areas have had time to build up an immunity to the disease. Professor Anna Färnert is studying this immunity. "We've shown that people continuously infected with several parasite strains have better immunity against the disease. This suggests that a future malaria vaccine should contain several components if it is to provide decent protection." Färnet's clinical research in Sweden has changed the medical view of immunity to severe malaria. It is not, as once though, permanent. "Patients originally from Africa but who have lived for a long time in other parts of the world lose this protection," she says. Ambitious moves against malaria Senior professor Anders Björkman has been researching malaria since the 1980s. One of his research tracks is Zanzibar, off the coast of Tanzania, where ambitious moves against malaria have long been in progress. "We're dealing with a combination of Artemisinin, impregnated mosquito net and other measures," he says. "One and a half million people live on these islands and these efforts have reduced the incidence of malaria by 97 per cent." Professor Akira Kaneko is also interested in islands, and has managed to make and keep the Pacific island of Aneityum, with its 700-strong population, entirely malaria-free. He now intends to repeat her successes in Lake Victoria. "We're looking at four islands and part of the mainland," he says. "We'll be launching a pilot study on a small island in January with a combination of measures, including drug therapy, for all 60,000 people in the area. Population mobility will bring new cases into the area, but we hope our strategy will bring the incidence of the disease down from 30 per cent to less than 1 per cent in four years." Resistence a serious concern All these malaria researchers share a serious concern about the growing resistance to artemisinin. Pedro Gil is one of many devoting his research to this threat. "We're researching the molecular mechanisms behind resistance in order to find optimal combinations of drugs for this," he says. "We hope to find combinations of components that the parasite won't be able to develop comprehensive resistance to; in other words, to put it in a Catch 22 situation – develop a resistance to A and be attacked by B, or vice versa. We're planning clinical trials in Mali for next year." Another way of dealing with the effects of resistance is to develop new drugs. "We've produced a candidate called Sevuparin, which operates according to a new principle: blocking a receptor to prevent the parasite from entering the red blood cells," explains Professor Mats Wahlgren. "We've recently completed a phase I/II study and have just sent the results in for publishing." Countries will be free from the diseases Resistance can also become a problem for the antiparasitic drug Ivermectin, says researcher Susanne Nylén. "There are no clear indications of resistant parasites in humans yet, but there are in livestock," she says. "But then again, Ivermectin is used much more for animals, so the pressure to develop resistance has been much greater there." So far, she notes, Ivermectin has been a very successful weapon in the battle against river blindness and lymphatic filariasis (elephantiasis): many countries are, or will soon be, free from the diseases, which might eventually be eradicated completely. Malaria, however, is much harder to combat. "We aim to have completely eradicated the disease by 2050, which is an enormous undertaking," says Professor Mats Wahlgren. Text: Anders Nilsson
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Factoring in weather variation to capture the influence of urban design and built environment on globally recommended levels of moderate to vigorous physical activity in children
Objectives
In curbing physical inactivity, as behavioural interventions directed at individuals have not produced a population-level change, an ecological perspective called active living research has gained prominence. However, active living research consistently underexplores the role played by a perennial phenomenon encompassing all other environmental exposures—variation in weather. After factoring in weather variation, this study investigated the influence of diverse environmental exposures (including urban design and built environment) on the accumulation of globally recommended moderate to vigorous physical activity levels (MVPA) in children.
DesignThis cross-sectional observational study is part of an active living initiative set in the Canadian prairie city of Saskatoon. As part of this study, Saskatoon's neighbourhoods were classified based on urban street design into grid-pattern, fractured grid-pattern and curvilinear types of neighbourhoods. Moreover, diverse environmental exposures were measured including, neighbourhood built environment, and neighbourhood and household socioeconomic environment. Actical accelerometers were deployed between April and June 2010 (spring-summer) to derive MVPA of 331 10–14-year-old children in 25 1-week cycles. Each cycle of accelerometry was conducted on a different cohort of children within the total sample and matched with weather data obtained from Environment Canada. Multilevel modelling using Hierarchical Linear and Non-linear Modelling software was conducted by factoring in weather variation to depict the influence of diverse environmental exposures on the accumulation of recommended MVPA.
ResultsUrban design, including diversity of destinations within neighbourhoods played a significant role in the accumulation of MVPA. After factoring in weather variation, it was observed that children living in neighbourhoods closer to the city centre (with higher diversity of destinations) were more likely to accumulate recommended MVPA.
ConclusionsThe findings indicate that after factoring in weather variation, certain types of urban design are more likely to be associated with MVPA accumulation.
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Recorded gonorrhoea rates in Denmark, 1900-2010: the impact of clinical testing activity and laboratory diagnostic procedures
Objectives
Assessment of the relations between recorded gonorrhoea rates and clinical testing activity and disposable diagnostic tests.
MethodsIn Denmark, two sources of information on the epidemiology of gonorrhoea are available: (1) a mandatory clinical notification system (since 1867) comprising summary information about geographic distribution, season, age group and gender; in 1994, more detailed anonymous individualised epidemiological information was included; (2) a voluntary countrywide laboratory surveillance system for culture-confirmed cases (since 1957) comprising information about patient's age and gender, infected anatomical sites and medical setting attended.
ResultsBoth surveillance systems showed marked simultaneous changes in gonorrhoea rates, although periodically considerable under-reporting or under-diagnosing was demonstrated. The annual incidence of notified cases peaked in 1919 (474/100 000), in 1944 (583/100 000) and in 1972 (344/100 000). Since 1995, the incidence has been at a low endemic level (1.5–10/100 000) and the total male/female incidence ratios were from 3 to 7 times higher than previously recorded. Among approximately 2 million persons tested during 1974–1988 78 213 men and 63 143 women with culture-confirmed gonorrhoea were identified. During this period, pharyngeal sampling was performed in 36% of men and 25% of women with gonorrhoea; pharyngeal gonorrhoea was found in 10% and 16%, respectively; 40% and 30% of these patients had no concomitant urogenital gonorrhoea. Among men with gonorrhoea, 34% were sampled from the rectum; 9% had rectal gonorrhoea, among whom the rectum was the only infected site in 67%.
ConclusionsCrucial factors for case finding are clinical sampling tradition and appropriate laboratory diagnostic facilities. When case finding is insufficient, a reservoir of asymptomatic rectal or pharyngeal gonorrhoea remains unrecognised.
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Depression and anxiety in ovarian cancer: a systematic review and meta-analysis of prevalence rates
Objectives
To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage.
DesignSystematic review and meta-analysis.
Participants3623 patients with ovarian cancer from primary research investigations.
Primary outcome measureThe prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage.
ResultsWe identified 24 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 3623 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 25.34% (CI 22.79% to 28.07%), 22.99% (CI 19.85% to 26.46%) and 12.71% (CI 10.14% to 15.79%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 19.12% (CI 17.11% to 21.30%), 26.23% (CI 22.30% to 30.56%) and 27.09% (CI 23.10% to 31.49%).
ConclusionsOur findings suggest that the prevalence of depression and anxiety in women with ovarian cancer, across the treatment spectrum, is significantly greater than in the healthy female population. With the growing emphasis on improving the management of survivorship and quality of life, we conclude that further research is warranted to ensure psychological distress in ovarian cancer is not underdiagnosed and undertreated.
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Incidence of knee cartilage surgery in Norway, 2008-2011
Objective
A systematic and long-term data collection on the treatment of focal cartilage defects (FCDs) of the knee is needed. This can be achieved through the foundation of a National Knee Cartilage Defect Registry. The aim of this study was to establish the nationwide burden of knee cartilage surgery, defined as knee surgery in patients with an FCD. We also aimed to identify any geographical differences in incidence rates, patient demographics or trends within this type of surgery.
SettingA population-based study with retrospective identification of patients undergoing knee cartilage surgery in Norway through a mandatory public health database from 2008 to 2011.
ParticipantsWe identified all patients undergoing cartilage surgery, or other knee surgery in patients with an FCD. All eligible surgeries were assessed for inclusion on the basis of certain types of ICD-10 and NOMESKO Classification of Surgical Procedures codes.
Primary and secondary outcome measuresThe variables were diagnostic and surgical codes, geographic location of the performing hospital, age and sex of the patients. Yearly incidence and incidence rates were calculated. Age-adjusted incidences for risk ratios and ORs between geographical areas were also calculated.
ResultsA total of 10 830 cases of knee cartilage surgery were identified, with slight but significant decreases from 2008 to 2011 (p<0.0003). The national incidence rate was 56/100 000 inhabitants and varied between regions, counties and hospitals. More than 50% of the procedures were palliative and nearly 400 yearly procedures were reparative or restorative.
ConclusionsKnee cartilage surgery is common in Norway, counting 2500 annual cases with an age-adjusted incidence rate of 68.8/100 000 inhabitants. There are significant geographical variations in incidence and trends of surgery and in trends between public and private hospitals. We suggest that a national surveillance system would be beneficial for the future evaluation of the treatment of these patients.
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Vitamin D status and associated metabolic risk factors among North Korean refugees in South Korea: a cross-sectional study
Objective
Vitamin D deficiency is now recognised as a common health problem associated with various chronic diseases; however, it has not been fully elucidated among the minority groups. Here, we aimed to investigate the prevalence of vitamin D deficiency and its associated metabolic risk factors among North Korean refugees living in South Korea.
DesignCross-sectional analysis from the longitudinal cohort, the North Korean refugee health in South Korea (NORNS) study.
ParticipantsA total of 386 North Korean refugees aged ≥30 years, who measured serum 25-hydroxy vitamin D (25(OH)D) level.
ResultsThe prevalence of vitamin D deficiency (25(OH)D <20 ng/mL) was 87% and no participants had an adequate vitamin D level (25(OH)D ≥30 ng/mL). Underweight participants (body mass index (BMI) <18 kg/m2) had significantly lower 25(OH)D levels than individuals with normal BMI (≥18.5 and<23 kg/m2). In the multivariate logistic regression analysis, the lowest 25(OH)D level (<10 ng/mL) was significantly associated with metabolic syndrome (OR, 6.37, 95% CI 1.34 to 30.3), high triglyceride (OR, 6.71, 95% CI 1.75 to 25.7), and low high-density lipoprotein (OR, 5.98, 95% CI 1.54 to 23.2) compared with 25(OH)D levels ≥20 ng/mL after adjusting for age, sex, season, length of residence in South Korea, physical activity and BMI.
ConclusionsVitamin D deficiency is very common among North Korean refugees in South Korea. Despite their lower BMI, vitamin D deficiency was associated with metabolic syndrome in this population.
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Organisation and function of the primary motor cortex in chronic pain: protocol for a systematic review and meta-analysis
Introduction
Primary motor cortical (M1) adaptation in the form of altered organisation and function is hypothesised to underpin motor dysfunction observed in chronic pain. The aim of this review is to assess the evidence for altered M1 organisation and function in chronic pain.
Methods and analysisSystematic review and meta-analysis. We will search electronic databases with predetermined search terms to identify relevant studies and evaluate the studies for inclusion and risks of bias. Two independent reviewers will extract data. Any disagreement will be resolved through a third reviewer. Cross-sectional or prospective studies published in English before May 2015 that investigate M1 organisation and function in chronic pain will be included if they meet the eligibility criteria. Primary outcomes will include M1 cortical excitability, spatial cortical representation, the function of inhibitory and facilitatory intracortical networks, cortical reactivity and cortical glucose metabolism. Clinical measures such as pain and disability will be included where the correlation with the primary outcomes of M1 organisation and function were investigated in the included studies.
Ethics and disseminationThis systematic review does not require ethical approval. The results of this review will be submitted for peer-reviewed publication regardless of outcome and will be presented at relevant conferences.
Trial registration numberOur systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42015014823).
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Identification of antithrombotic drugs related to total joint replacement using anonymised free-text notes: a search strategy in the Clinical Practice Research Datalink
Objectives
We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD).
SettingGeneral practice database representative of the UK.
ParticipantsAll patients undergoing total hip replacement (THR, n=25 898) or total knee replacement (TKR, n=22 231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data.
Primary and secondary outcome measuresInternal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics.
ResultsPPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use.
ConclusionsWe have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery.
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Patient experience of computerised therapy for depression in primary care
Objective
To explore patient experience of computerised cognitive behaviour therapy (cCBT) for depression in a pragmatic randomised controlled trial (Randomised Evaluation of the Effectiveness and Acceptability of Computerised Therapy, REEACT).
DesignQualitative semistructured interviews with 36 participants.
ParticipantsDepressed patients with a Patient Health Questionnaire 9 of 10 or above recruited into the REEACT randomised controlled trial.
SettingPrimary care settings in England.
ResultsParticipant experience was on a continuum, with some patients unable or unwilling to accept psychological therapy without interpersonal contact while others appreciated the enhanced anonymity and flexibility of cCBT. The majority of patients were ambivalent, recognising the potential benefits offered by cCBT but struggling with challenges posed by the severity of their illness, lack of support and limited personalisation of programme content. Low completion rates were commonly reported, although more positive patients reported greater engagement. Both positive and ambivalent patients perceived a need for monitoring or follow-up to support completion, while negative patients reported deliberate non-adherence due to dissatisfaction with the programme. Patients also reported that severity of depression impacted on engagement, and viewed cCBT as unsuitable for patients undergoing more severe depressive episodes.
ConclusionsThe study demonstrates both the unique demands and benefits of computerised therapy. cCBT was preferred by some patients and rejected by others, but the majority of patients were ambivalent about the therapy. cCBT could be offered within a menu of options in stepped care if matched appropriately to individual patients or could be offered with enhanced support to appeal to a greater number of patients.
Trial registration numberISRCTN91947481.
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Home oxygen therapy reduces risk of hospitalisation in patients with chronic obstructive pulmonary disease: a population-based retrospective cohort study, 2005-2012
Objective
This study evaluated the effect of home oxygen therapy (HOT) on hospital admissions in chronic obstructive pulmonary disease (COPD) patients.
Design and settingUsing nationwide health insurance claims from 2002–2012, we conducted a longitudinal population-based retrospective cohort study.
ParticipantsIndividuals who were aged 40 years or above and newly diagnosed with COPD in 2005.
Outcome measuresThe primary outcome was total number of hospitalisations during the study period. Participants were matched using HOT propensity scores and were stratified by respiratory impairment (grade 1: FEV1 ≤25% or PaO2 ≤55 mm Hg; grade 2: FEV1 ≤30% or PaO2 56–60 mm Hg; grade 3: FEV1 ≤40% or PaO2 61–65 mm Hg; 'no grade': FEV1 or PaO2 unknown), then a negative binomial regression analysis was performed for each group.
ResultsOf the 36 761 COPD patients included in our study, 1330 (3.6%) received HOT. In a multivariate analysis of grade 1 patients performed before propensity score matching, the adjusted relative risk of hospitalisation for patients who did not receive HOT was 1.27 (95% CI 1.01 to 1.60). In a multivariate analysis of grade 1 patients performed after matching, the adjusted relative risk for patients who did not receive HOT was 1.65 (95% CI 1.25 to 2.18). In grade 2 or grade 3 patients, no statistical difference in hospital admission risk was detected. In the 'no grade' group of patients, HOT was associated with an increased risk of hospitalisation.
ConclusionsHOT reduces the risk of hospital admission in COPD patients with severe hypoxaemia. However, apart from these patients, HOT use is not associated with hospital admissions.
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Association between sleeping hours and cardiometabolic risk factors for metabolic syndrome in a Saudi Arabian population
Objectives
Epidemiological and molecular studies have shown that sleep duration is associated with metabolic syndrome (MtS), a disease that is on the rise in the Kingdom of Saudi Arabia. We aim to investigate the association between sleep duration and selected cardiometabolic risk factors of MtS in a Saudi Arabian population.
SettingSecondary care was given to the participants. There were 2 participating centres, shopping malls in North and South Jeddah, Saudi Arabia.
ParticipantsWe recruited 2686 participants over a 1-year study period. Participants were selected based on their willingness. The only criterion for exclusion was living in the area (North or South Jeddah) for less than 15 years.
Planned and primary outcome measuresParticipants were measured for blood sugar levels, blood pressure and body mass index. All participants were asked to fill out a questionnaire.
ResultsThere was a positive association between longer sleep duration and obesity, hypertension and hyperglycaemia. The adjusted ORs for obesity, hypertension and hyperglycaemia were 1.54 (95% CI 1.20 to 1.98), 1.89 (95% CI 1.45 to 2.48) and 1.59 (95% CI 1.19 to 2.13), respectively, in participants sleeping >8 h/night, as compared with those sleeping 7 h. The positive associations between longer sleep duration, defined as sleeping >7 h, and the disease status, did not differ from other risk factors such as physical activity and nutrition.
ConclusionsThis is the first epidemiological study reporting on the association between sleep duration and cardiometabolic risk factors of MtS in a Saudi Arabian population. Sleep durations of 8 h or greater were found to be associated with all 3 cardiometabolic risk factors: obesity, hypertension and hyperglycaemia, and this relationship was not confounded by quality of nutrition or physical activity levels.
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Preventing obesity in infants: the Growing healthy feasibility trial protocol
Introduction
Early childhood is an important period for establishing behaviours that will affect weight gain and health across the life course. Early feeding choices, including breast and/or formula, timing of introduction of solids, physical activity and electronic media use among infants and young children are considered likely determinants of childhood obesity. Parents play a primary role in shaping these behaviours through parental modelling, feeding styles, and the food and physical activity environments provided. Children from low socio-economic backgrounds have higher rates of obesity, making early intervention particularly important. However, such families are often more difficult to reach and may be less likely to participate in traditional programs that support healthy behaviours. Parents across all socio-demographic groups frequently access primary health care (PHC) services, including nurses in community health services and general medical practices, providing unparalleled opportunity for engagement to influence family behaviours. One emerging and promising area that might maximise engagement at a low cost is the provision of support for healthy parenting through electronic media such as the Internet or smart phones. The Growing healthy study explores the feasibility of delivering such support via primary health care services.
MethodsThis paper describes the Growing healthy study, a non-randomised quasi experimental study examining the feasibility of an intervention delivered via a smartphone app (or website) for parents living in socioeconomically disadvantaged areas, for promoting infant feeding and parenting behaviours that promote healthy rather than excessive weight gain. Participants will be recruited via their primary health care practitioner and followed until their infant is 9 months old. Data will be collected via web-based questionnaires and the data collected inherently by the app itself.
Ethics and disseminationThis study received approval from the University of Technology Sydney Ethics committee and will be disseminated via peer-reviewed publications and conference presentations.
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Nutrition interventions for children aged less than 5 years following natural disasters: a systematic review protocol
Introduction
Malnutrition among children is a serious public health problem in the aftermath of any natural disaster. We will review the various nutrition interventions for children aged <5 years in countries where natural disasters occurred and analyse the effect on nutrition-related outcomes.
Methods and analysisWe will conduct a systematic review on nutrition intervention studies following natural disasters that were published between January 2000 and December 2015. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Cochrane Risk of Bias (RoB) tool will be used for randomised controlled trials and Risk of Bias Assessment for Non-Randomized Studies (RoBANS) will be used for non-randomised studies. The quality of evidence will be assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. If sufficient data are available, we will conduct meta-analyses to establish the relationship between nutrition interventions and nutrition outcome indicators. All statistical analyses will be performed using Review Manager (Rev Man) V.5.3 for Windows. Heterogeneity of the data will be tested using the standard 2 test. A fixed-effect model will be used for the studies with high heterogeneity (p value>0.10, I2≤50%). For dichotomous and continuous data, relative risk (RR) and mean difference with 95% CI will be used respectively. Subgroup analysis will be performed for studies with low heterogeneity (p value ≤0.10). We will use Z score with the level of significance set at p value <0.05 to test the total effect. Funnel plots will be used to detect publication bias.
Ethics and disseminationAs primary data will not be collected, formal ethical approval will not be required. The results will be disseminated by publication in peer-reviewed journals, conference presentations and the media.
Registration detailsInternational Prospective Register for Systematic Reviews (PROSPERO) number CRD42015023243 was registered on 1 June 2015.
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Gene expression signatures, pathways and networks in carotid atherosclerosis
Abstract
Background
Embolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability.
Methods
Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed.
Results
These studies revealed upregulation of haemoglobin metabolism (P = 2.20E-05) and bone resorption (P = 9.63E-04) in S patients. Analysis of subgroups of patients indicated enrichment of calcification and osteoblast differentiation in S patients on statins, as well as inflammation and apoptosis in plaques removed >1 month compared to <2 weeks after symptom. By prediction profiling, a panel of 30 genes, mostly transcription factors, discriminated between plaques from S versus AS patients with 78% accuracy. By meta-analysis, common gene networks associated with atherosclerosis mapped to hypoxia, chemokines, calcification, actin cytoskeleton and extracellular matrix. A set of dysregulated genes (LMOD1, SYNPO2, PLIN2 and PPBP) previously not described in atherosclerosis were identified from microarrays and validated by quantitative PCR and immunohistochemistry.
Conclusions
Our findings confirmed a central role for inflammation and proteases in plaque instability, and highlighted haemoglobin metabolism and bone resorption as important pathways. Subgroup analysis suggested prolonged inflammation following the symptoms of plaque instability and calcification as a possible stabilizing mechanism by statins. In addition, transcriptional regulation may play an important role in the determination of plaque phenotype. The results from this study will serve as a basis for further exploration of molecular signatures in carotid atherosclerosis.
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Platelet transfusions in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit
Background: Thrombocytopenia is a frequent finding in critically ill cancer patients for whom indications of platelet transfusions are unclear. We herein addressed the current practices in platelet transfusion and the risk of bleeding in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit (ICU). Methods: A retrospective monocenter study over a 7-year period was conducted in a medical ICU. Adult patients with malignancies and hypoproliferative thrombocytopenia, and who received at least one platelet concentrate during their ICU stay, were included. Results: 296 patients were included and received a total of 904 platelet transfusions, for prophylactic indications in 300 (33.2 %) episodes, for securing an invasive procedure in 257 (28.4 %), and for treatment of minor to major bleeding manifestations in 347 (38.4 %). Most prophylactic transfusions (80 %) were performed at platelet count thresholds below 10–20 × 10 9 /L. Platelet increments were generally low in all three indications, 10 (interquartile range 2–25), 11 (2–25), and 8 (0–21) × 10 9 /L, respectively. A total of 97 major ICU-acquired bleeding events occurred in 40 patients. About half of those bleeding episodes (54.7 %) occurred at platelet counts below 20 × 10 9 /L. However, neither low admission platelet count nor low nadir platelet counts were predictive of ICU-acquired bleeding. The in-ICU mortality rate tended to be higher in patients with severe ICU-acquired bleeding events (50 vs. 36 %). Conclusions: Most prophylactic platelet transfusions were given using thresholds of 10–20 × 10 9 /L in critically ill thrombocytopenic cancer patients. The individual risk of ICU-acquired severe bleeding appears hardly predictable with the depth of thrombocytopenia.
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Infective endocarditis requiring ICU admission: epidemiology and prognosis
Background: Very few studies focused on patients with severe infective endocarditis (IE) and multiple complications leading to Intensive Care Unit (ICU) admission. Studied primary outcomes depended on the series and multiple prognostic factors have been identified. Our goal was to determinate characteristics of patients, in-hospital mortality and independent prognostic factors in an overall population of patients admitted to ICU for a left-sided, definite, active and severe IE. Methods: Retrospective study performed in 9 ICUs during an 11-year period. Results: Data of 248 patients (mean age = 62.4 ± 13.3 years; 63.7 % male) were studied. Native and prosthetic valves were involved in 195 and 53 patients, respectively. Causative pathogens, identified in 225 patients, were mainly streptococci (45.6 %) and staphylococci (43.4 %). On ICU admission, 127 patients exhibited extra-cardiac involvement. Ninety-five patients had one or more neurological complications, as followed: ischemic stroke (n = 66), cerebral hemorrhage (n = 31), meningitis (n = 16), brain abscess (n = 16), and intracranial mycotic aneurysm (n = 10). Criteria prompting to cardiac surgery appeared during ICU stay for 186 patients and between ICU and hospital discharges in 5 patients. Due to contra-indications, surgery required by IE was only performed during hospitalization in 125 patients. Moreover, surgery was considered adequate according to usual guidelines in 76 of 191 patients with indication(s) of valvular surgery: for patients with surgical procedure considered as emergency (n = 69), 17 surgical procedures underwent within the first 24 h following indication; for patients with urgent surgical indication (n = 102), surgery was performed during the first week following indication in 40 patients; finally, elective surgery (n = 20) was performed for 19 patients. During hospitalization, 103 (41.5 %) patients died. Four independent prognostic factors were identified: SAPS II > 35 (AOR = 2.604; 95 % CI: 1.320–5.136; p = 0.0058), SOFA > 8 (AOR = 3.327; 95 % CI: 1.697–6.521; p = 0.0005), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981; 95 %CI = 1.433–17.306; p = 0.0115) and native IE (AOR = 0.345; 95 % CI: 0.169–0.703; p = 0.0034). Conclusions: Mortality in patients admitted to ICU for left-sided IE remains high, especially in cases of endocarditis due to methicillin resistant Staphylococcus aureus, when organ failures occur and ICU scores are high.
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Bounding the per-protocol effect in randomized trials: an application to colorectal cancer screening
Background: The per-protocol effect is the effect that would have been observed in a randomized trial had everybody followed the protocol. Though obtaining a valid point estimate for the per-protocol effect requires assumptions that are unverifiable and often implausible, lower and upper bounds for the per-protocol effect may be estimated under more plausible assumptions. Strategies for obtaining bounds, known as "partial identification" methods, are especially promising in randomized trials. Results: We estimated bounds for the per-protocol effect of colorectal cancer screening in the Norwegian Colorectal Cancer Prevention trial, a randomized trial of one-time sigmoidoscopy screening in 98,792 men and women aged 50–64 years. The screening was not available to the control arm, while approximately two thirds of individuals in the treatment arm attended the screening. Study outcomes included colorectal cancer incidence and mortality over 10 years of follow-up. Without any assumptions, the data alone provide little information about the size of the effect. Under the assumption that randomization had no effect on the outcome except through screening, a point estimate for the risk under no screening and bounds for the risk under screening are achievable. Thus, the 10-year risk difference for colorectal cancer was estimated to be at least −0.6 % but less than 37.0 %. Bounds for the risk difference for colorectal cancer mortality (–0.2 to 37.4 %) and all-cause mortality (–5.1 to 32.6 %) had similar widths. These bounds appear helpful in quantifying the maximum possible effectiveness, but cannot rule out harm. By making further assumptions about the effect in the subpopulation who would not attend screening regardless of their randomization arm, narrower bounds can be achieved. Conclusions: Bounding the per-protocol effect under several sets of assumptions illuminates our reliance on unverifiable assumptions, highlights the range of effect sizes we are most confident in, and can sometimes demonstrate whether to expect certain subpopulations to receive more benefit or harm than others.Trial registrationClinicaltrials.gov identifier NCT00119912 (registered 6 July 2005)
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Multi Tonal Tinnitus
Many people experience the periodic sensation of ringing in the ears as well as other transient noises that usually only last a few minutes. The pitch of these sounds can range from high to low tones. Tinnitus is the primary reason for phantom ringing, roaring, hissing or buzzing sounds that do not get better or go away. The condition is defined as audible noises not caused by outside stimulus. Symptoms can appear suddenly or gradually over time. You may experience single or multi tonal tinnitus in one or both ears. The noises may be low and intermittent or loud and continuous. Multi tonal tinnitus may involve two or more sounds of varying pitch, tone, rhythm and volume in one both ears.
Types of Tinnitus
Accounting for roughly 5 percent of tinnitus sufferers, objective tinnitus is generally associated with muscular or vascular disorders. The sounds for this type of multi tonal tinnitus pulsate with the rhythm of your breathing or heartbeat. They may be heard through a stethoscope during a physical examination. The remaining approximately 95 percent of patients have subjective tinnitus, which are sounds only you can hear. Many factors can cause subjective tinnitus like problems with auditory nerves and the way the brain interprets signals. Other causes include perforated eardrums, ear infections, allergies and benign tumors as well as traumatic hearing loss.
Effect on Quality of Life
Multi tonal tinnitus can significantly affect your quality of life. Although the condition affects people differently, it can cause fatigue and stress resulting from difficulty in falling asleep, irritation and interrupted concentration along with memory problems. These factors can eventually interfere with personal and professional relationships as well as create a sense of apprehension or other feelings of emotional distress. While many tinnitus sufferers also have hearing loss, the condition does not mean that you will lose your hearing.
Treatments
Multi tonal tinnitus is a condition that in most cases will not improve on its own. You should seek professional treatment as soon as possible. If the tinnitus is caused by an underlying medical condition, treating that ailment may eliminate the tinnitus. Your health care provider may also recommend medication, masking devices or other alternative treatments, such as nutritional management. Masking, or acoustic therapy, utilizes other sounds to cover up or alter the sounds present in your tinnitus. Stress management counseling and cognitive behavioral therapy can help reduce the stress associated with the condition.
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Improving the organisation of maternal health service delivery and optimising childbirth by increasing vaginal birth after caesarean section through enhanced women-centred care (OptiBIRTH trial): study protocol for a randomised controlled trial (ISRCTN10612254)
Background: The proportion of pregnant women who have a caesarean section shows a wide variation across Europe, and concern exists that these proportions are increasing. Much of the increase in caesarean sections in recent years is due to a cascade effect in which a woman who has had one caesarean section is much more likely to have one again if she has another baby. In some places, it has become common practice for a woman who has had a caesarean section to have this procedure again as a matter of routine. The alternative, vaginal birth after caesarean (VBAC), which has been widely recommended, results in fewer undesired results or complications and is the preferred option for most women. However, VBAC rates in some countries are much lower than in other countries.Methods/DesignThe OptiBIRTH trial uses a cluster randomised design to test a specially developed approach to try to improve the VBAC rate. It will attempt to increase VBAC rates from 25 % to 40 % through increased women-centred care and women's involvement in their care. Sixteen hospitals in Germany, Ireland and Italy agreed to join the study, and each hospital was randomly allocated to be either an intervention or a control site.DiscussionIf the OptiBIRTH intervention succeeds in increasing VBAC rates, its application across Europe might avoid the 160,000 unnecessary caesarean sections that occur every year at an extra direct annual cost of more than €150 million.Trial registrationCurrent Controlled Trials ISRCTN10612254, registered 3 April 2013.
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Comparison of treatment outcomes of endoscope-guided pneumatic dilation and laparoscopic Heller myotomy
Publication date: Available online 30 November 2015
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Hsin-Ming Wang, Wei-Chen Tai, Seng-Kee Chuah, Hung-I Lu, Lung-Sheng Lu, Chih-Ming Liang, Chung-Huang Kuo, Yi-Chun Chiu, Keng-Liang Wu, Chi-Sin Changchien
The debate on which is the better choice between laparoscopic Heller myotomy (LHM) and endoscopic pneumatic dilation (PD) for esophageal achalasia has been ongoing for decades. This study aims to compare the results of endoscope-guided PD and LHM in 42 patients with achalasia between May 1996 and August 2011. Twenty-one patients who had received PD and 21 who had received LHM were enrolled. The cumulative remission rate was analyzed using the Kaplan–Meier method with the assessment of symptom scores between grades before and after PD or LHM done at 6 weeks, 6 months, 1 year, and then every year thereafter. Possible confounding factors related to the remissions were analyzed by Cox's proportional hazard model. For PD, the cumulative remission rates were 81.0% (1 year), 76.2% (2), 66.7% (3), 61.9% (4), and 47.6% (5). For LHM, the cumulative remission rates were 90.5% every year from the 1st to the 5th. The LHM patients had significantly better remission rates than the PD patients (p = 0.033, by log-rank test). The LHM group had a longer hospital stay than the PD group [median (interquartile range): 8 (6.5–10) days vs. 3 (2–3) days, p < 0.001) and had more reflux complications (52.4% vs. 19.0%, p = 0.024). No perforation occurred in either group. In conclusion, the 5-year cumulative effectiveness of LHM is better than that of PD despite the association of LHM with more reflux events (52.4%).
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Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro
Publication date: Available online 30 November 2015
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Lin Hou, Qiang Dong, Yun-jian Wu, Yuan-xing Sun, Yan-yu Guo, Yue-hong Huo
Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8–13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3β-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3β-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels.
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Association of HLA and cytokine gene polymorphisms with idiopathic pulmonary fibrosis
Publication date: Available online 30 November 2015
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Hai-Ping Zhang, Jian Zou, Ping Xie, Fei Gao, Hui-Jun Mu
Idiopathic pulmonary fibrosis (IPF) is a rare, progressive, and lethal interstitial lung disease with unknown etiology. Divergent observations have suggested that genetic factors contribute to IPF susceptibility. This study investigated the relationship between human leukocyte antigen (HLA), cytokine gene polymorphisms, and IPF in a Chinese Han population. The gene polymorphisms of HLA-A, -B, -DRB1, tumor necrosis factor alpha [TNF-α (−308 A/G)], transforming growth factor beta [TGF-β1 (+869 T/C)], interleukin 10 [IL-10 (−592 C/A, −819 T/C, and −1082 G/A)], and interferon gamma [IFN-γ (+874 T/A)] were detected in 102 individuals with IPF and 266 unrelated normal controls using PCR with sequence-specific primers and a high-resolution melt (HRM) approach. The data showed that there was no difference in HLA allele frequencies between the IPF and control groups. However, the data showed the frequency of HLA-A*02-DRB1*04 haplotype in the IPF group was significantly higher than that in the control group [odds ratio (OR) = 4.69, 95% confidence interval (CI) = 1.82–12.08, p < 0.001]. In addition, no differences in the allele and genotype distributions of the cytokines were found between the IPF and control groups (p > 0.01). Our findings suggest that there is an association between specific HLA haplotype and IPF genetic susceptibility and that the genetic variability of some cytokines may not be involved in the pathogenesis of IPF.
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Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology
CytoJournal 2015 12(1):26-26
To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only. [1],[2] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower. [3],[4],[5] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy. [6],[7] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.
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Collagenous spherulosis: An interesting cytological finding in breast lesion
CytoJournal 2015 12(1):25-25
Collagenous spherulosis (CS) is a rare and interesting entity associated with benign breast lesions. CS is an incidental finding picked up only on 0.2% of cytology specimen. Typically cytologically of CS of breast consists of central spherical hyaline spherule surrounded by myoepithelial cells. The central hyaline spherule has been found to be basement membrane material histochemically and immunohistochemically. The importance of recognizing CS of breast lies in the fact that similar hyaline globules can occur in adenoid cystic carcinoma of the breast (ACCB). The two lesions need to be differentiated on cytology failing which inappropriate treatment can be given for either of the two lesions. We present here a case of CS associated with benign breast lesion and a case of ACCB to describe their cytological features and key points to differentiate them cytologically.
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Pitfall in immunohistochemical staining for thyroglobulin in case of thyroid metastasis from lung carcinoma
CytoJournal 2015 12(1):27-27
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Geomagnetic Field (Gmf) and Plant Evolution: Investigating the Effects of Gmf Reversal on Arabidopsis thaliana Development and Gene Expression
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Analysis of Zebrafish Larvae Skeletal Muscle Integrity with Evans Blue Dye
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Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting
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An emerging concern: Toxic fumes in airplane cabins
Publication date: Available online 30 November 2015
Source:Cortex
Author(s): Virginia Harrison, Sarah J. Mackenzie Ross
Toxicology is a new science, the complexities of which have been highlighted in the papers contained within this special section. Our understanding of the mechanisms through which various chemicals interfere with nervous system function is constantly evolving and research is unable to keep up with the speed with which new chemicals are produced and put onto the market. Thus there are often controversies surrounding the health-effects of commercially available compounds and disagreement around what constitutes safe exposure limits. This article will introduce readers to an emerging concern in this field, the potential risk to health of toxic fumes in airplane cabins. We explore the challenges and methodological issues encountered by researchers who have tried to investigate this issue and highlight the need for further research on this topic. We hope this article will promote discussion amongst academics and clinicians, and lead to the identification of creative solutions to the methodological issues encountered to date.
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Notice of Retraction: Ramipril Markedly Improves Walking Ability in Patients With Peripheral Arterial Disease [Summary for Patients]
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Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection A Randomized Trial
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Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality
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Behavioral Programs for Type 1 Diabetes Mellitus A Systematic Review and Meta-analysis
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Behavioral Programs for Type 2 Diabetes Mellitus A Systematic Review and Network Meta-analysis
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Applied Sciences, Vol. 5, Pages 1440-1456: 2D Saturable Absorbers for Fibre Lasers
Two-dimensional (2D) nanomaterials are an emergent and promising platform for future photonic and optoelectronic applications. Here, we review recent progress demonstrating the application of 2D nanomaterials as versatile, wideband saturable absorbers for Q-switching and mode-locking fibre lasers. We focus specifically on the family of few-layer transition metal dichalcogenides, including MoS2, MoSe2 and WS2.
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IJMS, Vol. 16, Pages 28334-28346: Carbon Ion Irradiated Neural Injury Induced the Peripheral Immune Effects in Vitro or in Vivo
Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3+CD4−CD8+ T-cells in the thymus and the proportion of CD3+CD4+CD8− T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation.
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Animals, Vol. 5, Pages 1207-1219: A Review of Different Stunning Methods for Poultry—Animal Welfare Aspects (Stunning Methods for Poultry)
Electrical water bath stunning is the most commonly used method for poultry stunning prior to slaughter, but has been questioned on animal welfare and product quality grounds. Controlled atmosphere stunning (CAS) methods, involving a variety of gas mixtures, have become increasingly common, at least in Europe. CAS methods have been perceived as an improvement from an animal welfare perspective, partly because birds can be stunned without prior shackling, and are generally considered to result in improved product quality compared to water bath stunning. However, there would still be an interest in alternative stunning methods especially for small to medium size poultry slaughterhouses. This review presents an overview of the modes of action and the technical aspects of poultry stunning methods, including novel and emerging stunning technologies.
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IJMS, Vol. 16, Pages 28320-28333: Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice
Adenylyl Cyclase 3 (AC3) plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE). In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/−) and wild-type (AC3+/+) mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels between AC3−/− and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up regulated, and 1988 were down regulated, including 425 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE.
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Molecules, Vol. 20, Pages 21204-21213: Metabolic Characteristics in Meal of Black Rapeseed and Yellow-Seeded Progeny of Brassica napus–Sinapis alba Hybrids
Breeding of yellow-seeded rapeseed (Brassica napus) is preferred over black-seeded rapeseed for the desirable properties of the former. This study evaluated the metabolites and nutritive values of black-seeded rapeseed meal and yellow-seeded meal from the progeny of a B. napus–Sinapis alba hybrid. Yellow-seed meal presented higher protein (35.46% vs. 30.29%), higher sucrose (7.85% vs. 7.29%), less dietary fiber (26.19% vs. 34.63%) and crude fiber (4.56% vs. 8.86%), and less glucosinolates (22.18 vs. 28.19 μmol/g) than black-seeded one. Amounts of ash (3.65% vs. 4.55%), phytic acid (4.98% vs. 5.60%), and total polyphenols (2.67% vs. 2.82%) were decreased slightly in yellow-seeded meal compared with black-seeded meal. Yellow-seeded meal contained more essential amino acids than black-seeded meal. Levels of the mineral elements Fe, Mn, and Zn in yellow-seeded meal were higher than black-seeded meal. By contrast, levels of P, Ca, and Mg were lower in yellow-seeded meal. Moreover, yellow-seeded meal showed lower flavonol (kaempferol, quercetin, isorhamnetin, and their derivatives) content than black-seeded meal. Comparison of metabolites between yellow and black rapeseed confirmed the improved nutritional value of meal from yellow-seeded B. napus, and this would be helpful to the breeding and improvement of rapeseed for animal feeding.
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IJMS, Vol. 16, Pages 28311-28319: RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator
The alternative sigma factor RpoN regulates many cell functions, such as motility, quorum sensing, and virulence in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa often evolves rpoN-negative variants during the chronic infection in cystic fibrosis patients. It is unclear how RpoN interacts with other regulatory mechanisms to control virulence of P. aeruginosa. In this study, we show that RpoN modulates the function of PqsR, a quorum sensing receptor regulating production of virulence factors including the phenazine pyocyanin. The ∆rpoN mutant is able to synthesize 4-quinolone signal molecule HHQ but unable to activate PqsR and Pseudomonas quinolone signal (pqs) quorum sensing. The ∆rpoN mutant produces minimal level of pyocyanin and is unable to produce the anti-staphylococcal agents. Providing pqsR in trans in the ∆rpoN mutant restores its pqs quorum sensing and virulence factor production to the wild-type level. Our study provides evidence that RpoN has a regulatory effect on P. aeruginosa virulence through modulating the function of the PqsR quorum sensing regulator.
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Animals, Vol. 5, Pages 1220-1232: Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks
In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment.
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Molecules, Vol. 20, Pages 21232-21253: Hydrothermal Conversion of Giant Reed to Furfural and Levulinic Acid: Optimization of the Process under Microwave Irradiation and Investigation of Distinctive Agronomic Parameters
The hydrothermal conversion of giant reed (Arundo donax L.) to furfural (FA) and levulinic acid (LA) was investigated in the presence of dilute hydrochloric acid. FA and LA yields were improved by univariate optimization of the main reaction parameters: concentration of the acid catalyst, solid/liquid ratio of the reaction mixture, hydrolysis temperature, and reaction time. The catalytic performances were investigated adopting the efficient microwave (MW) irradiation, allowing significant energy and time savings. The best FA and LA yields were further confirmed using a traditionally heated autoclave reactor, giving very high results, when compared with the literature. Hydrolysis temperature and time were the main reaction variables to be carefully optimized: FA formation needed milder reaction conditions, while LA more severe ones. The effect of the crop management (e.g., harvest time) on FA/LA production was discussed, revealing that harvest time was not a discriminating parameter for the further optimization of both FA and LA production, due to the very high productivity of the giant reed throughout the year. The promising results demonstrate that giant reed represents a very interesting candidate for a very high contemporary production of FA and LA of up to about 70% and 90% of the theoretical yields, respectively.
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IJERPH, Vol. 12, Pages 15129-15142: Feasibility of Measuring Tobacco Smoke Air Pollution in Homes: Report from a Pilot Study
Tobacco smoke air pollution (TSAP) measurement may persuade parents to adopt smoke-free homes and thereby reduce harm to children from tobacco smoke in the home. In a pilot study involving 29 smoking families, a Sidepak was used to continuously monitor home PM2.5 during an 8-h period, Sidepak and/or Dylos monitors provided real-time feedback, and passive nicotine monitors were used to measure home air nicotine for one week. Feedback was provided to participants in the context of motivational interviews. Home PM2.5 levels recorded by continuous monitoring were not well-accepted by participants because of the noise level. Also, graphs from continuous monitoring showed unexplained peaks, often associated with sources unrelated to indoor smoking, such as cooking, construction, or outdoor sources. This hampered delivery of a persuasive message about the relationship between home smoking and TSAP. By contrast, immediate real-time PM2.5 feedback (with Sidepak or Dylos monitor) was feasible and provided unambiguous information; the Dylos had the additional advantages of being more economical and quieter. Air nicotine sampling was complicated by the time-lag for feedback and questions regarding shelf-life. Improvement in the science of TSAP measurement in the home environment is needed to encourage and help maintain smoke-free homes and protect vulnerable children. Recent advances in the use of mobile devices for real-time feedback are promising and warrant further development, as do accurate methods for real-time air nicotine air monitoring.
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Sensors, Vol. 15, Pages 29882-29892: Identification of Chinese Herbs Using a Sequencing-Free Nanostructured Electrochemical DNA Biosensor
Due to the nearly identical phenotypes and chemical constituents, it is often very challenging to accurately differentiate diverse species of a Chinese herbal genus. Although technologies including DNA barcoding have been introduced to help address this problem, they are generally time-consuming and require expensive sequencing. Herein, we present a simple sequencing-free electrochemical biosensor, which enables easy differentiation between two closely related Fritillaria species. To improve its differentiation capability using trace amounts of DNA sample available from herbal extracts, a stepwise electrochemical deposition of reduced graphene oxide (RGO) and gold nanoparticles (AuNPs) was adopted to engineer a synergistic nanostructured sensing interface. By using such a nanofeatured electrochemical DNA (E-DNA) biosensor, two Chinese herbal species of Fritillaria (F. thunbergii and F. cirrhosa) were successfully discriminated at the DNA level, because a fragment of 16-mer sequence at the spacer region of the 5S-rRNA only exists in F. thunbergii. This E-DNA sensor was capable of identifying the target sequence in the range from 100 fM to 10 nM, and a detection limit as low as 11.7 fM (S/N = 3) was obtained. Importantly, this sensor was applied to detect the unique fragment of the PCR products amplified from F. thunbergii and F. cirrhosa, respectively. We anticipate that such a direct, sequencing-free sensing mode will ultimately pave the way towards a new generation of herb-identification strategies.
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IJERPH, Vol. 12, Pages 15075-15087: A Comparative Study on the Uptake and Toxicity of Nickel Added in the Form of Different Salts to Maize Seedlings
In soil ecotoxicological studies, a toxic metal is usually added in the form of either an inorganic or organic salt with relatively high solubility. Nitrate, chloride, acetate, or sulfate are commonly considered as valid options for that aim. However, recent studies have shown that different salts of the same metal at the same cationic concentration may exhibit different toxicities to plants and soil organisms. This information should be considered when selecting data to use for developing toxicological criteria for soil environment. A comparative study was carried out to evaluate the toxicity of five nickel (Ni) salts: NiCl2, NiSO4, Ni(II)-citrate, Ni(CH3COO)2, and Ni(II)-EDTA (ethylenediaminetetraacetate), on maize seedlings. The plant metrics used were plant height, shoot and root biomass, leaf soluble sugars and starch, and the Ni contents of the shoots and roots. The results indicated that when Ni was added to the soil, toxicity varied with the selected anionic partner with the following toxicity ranking NiSO4 < Ni(CH3COO)2 < Ni(II)-citrate < NiCl2 < Ni(II)-EDTA. Taking the plant-height metric as an example, the effective concentrations for 50% inhibition (EC50) were 3148 mg·kg−1 for NiSO4, 1315 mg·kg−1 for NiCl2, and 89 mg·kg−1 for Ni(II)-EDTA. Compared with the Ni in the other salts, that in Ni(II)-EDTA was taken up the most efficiently by the maize roots and, thus, resulted in the greatest toxic effects on the plants. Nickel generally reduced leaf soluble sugars, which indicated an effect on plant carbohydrate metabolism. The outcome of the study demonstrates that different salts of the same metal have quite different ecotoxicities. Therefore, the anionic counterpart of a potentially toxic metal cation must be taken into account in the development of ecotoxicological criteria for evaluating the soil environment, and a preferred approach of leaching soil to reduce the anionic partner should also be considered.
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Sensors, Vol. 15, Pages 29871-29881: Temperature Effects on the Wind Direction Measurement of 2D Solid Thermal Wind Sensors
For a two-dimensional solid silicon thermal wind sensor with symmetrical structure, the wind speed and direction information can be derived from the output voltages in two orthogonal directions, i.e., the north-south and east-west. However, the output voltages in these two directions will vary linearly with the ambient temperature. Therefore, in this paper, a temperature model to study the temperature effect on the wind direction measurement has been developed. A theoretical analysis has been presented first, and then Finite Element Method (FEM) simulations have been performed. It is found that due to symmetrical structure of the thermal wind sensor, the temperature effects on the output signals in the north-south and east-west directions are highly similar. As a result, the wind direction measurement of the thermal wind sensor is approximately independent of the ambient temperature. The experimental results fit the theoretical analysis and simulation results very well.
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IJERPH, Vol. 12, Pages 15118-15128: Epidemiology of Unintentional Child Injuries in the Makwanpur District of Nepal: A Household Survey
Secondary sources of information indicate that the proportion of child deaths due to injuries is increasing in Nepal. This study aimed to describe the epidemiology of unintentional injuries in children, explore risk factors and estimate the burden faced by families and the community in the Makwanpur district. We conducted a household survey in Makwanpur, covering 3441 households. Injuries that occurred during the 12 months before the survey and required treatment or caused the child to be unable to take part in usual activities for three or more days were included. We identified 193 cases of non-fatal unintentional child injuries from 181 households and estimated an annual rate of non-fatal injuries of 24.6/1000 children; rates for boys were double (32.7/1000) that for girls (16.8/1000). The rates were higher among the children of age groups 1–4 years and 5–9 years. Falls were the most common cause of non-fatal child injuries followed by burns in preschool children and road traffic injuries were the most likely cause in adolescence. Mean period of disability following injury was 25 days. The rates and the mechanisms of injury vary by age and gender. Falls and burns are currently the most common mechanisms of injury amongst young children around rural homes.
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IJMS, Vol. 16, Pages 28296-28310: The Importance of Caveolin-1 as Key-Regulator of Three-Dimensional Growth in Thyroid Cancer Cells Cultured under Real and Simulated Microgravity Conditions
We recently demonstrated that the CAV1 gene was down-regulated, when poorly differentiated thyroid FTC-133 cancer cells formed spheroids under simulated microgravity conditions. Here, we present evidence that the caveolin-1 protein is involved in the inhibition of spheroid formation, when confluent monolayers are exposed to microgravity. The evidence is based on proteins detected in cells and their supernatants of the recent spaceflight experiment: "NanoRacks-CellBox-Thyroid Cancer". The culture supernatant had been collected in a special container adjacent to the flight hardware incubation chamber and stored at low temperature until it was analyzed by Multi-Analyte Profiling (MAP) technology, while the cells remaining in the incubation chamber were fixed by RNAlater and examined by mass spectrometry. The soluble proteins identified by MAP were investigated in regard to their mutual interactions and their influence on proteins, which were associated with the cells secreting the soluble proteins and had been identified in a preceding study. A Pathway Studio v.11 analysis of the soluble and cell-associated proteins together with protein kinase C alpha (PRKCA) suggests that caveolin-1 is involved, when plasminogen enriched in the extracellular space is not activated and the vascular cellular adhesion molecule (VCAM-1) mediated cell–cell adhesion is simultaneously strengthened and activated PRKCA is recruited in caveolae, while the thyroid cancer cells do not form spheroids.
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IJERPH, Vol. 12, Pages 15110-15117: Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China
Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.
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IJERPH, Vol. 12, Pages 15143-15153: The Geographic Distribution of Liver Cancer in Canada Does Not Associate with Cyanobacterial Toxin Exposure
Background: The incidence of liver cancer has been increasing in Canada over the past decade, as has cyanobacterial contamination of Canadian freshwater lakes and drinking water sources. Cyanotoxins released by cyanobacteria have been implicated in the pathogenesis of liver cancer. Objective: To determine whether a geographic association exists between liver cancer and surrogate markers of cyanobacterial contamination of freshwater lakes in Canada. Methods: A negative binomial regression model was employed based on previously identified risk factors for liver cancer. Results: No association existed between the geographic distribution of liver cancer and surrogate markers of cyanobacterial contamination. As predicted, significant associations existed in areas with a high prevalence of hepatitis B virus infection, large immigrant populations and urban residences. Discussion and Conclusions: The results of this study suggest that cyanobacterial contamination of freshwater lakes does not play an important role in the increasing incidence of liver cancer in Canada.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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