To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC).
A pooled analysis of four ...phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data.
The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors compared with 197 (6.8%) of patients with proficient MMR (pMMR) tumors (P < 0.001). In the pooled dataset, median PFS and OS were significantly worse for patients with dMMR compared with pMMR tumors HR, 1.33; 95% confidence interval (CI), 1.12-1.57 and HR, 1.35; 95% CI, 1.13-1.61, respectively), and for patients with BRAF(MT) compared with BRAF wild-type (BRAF(WT)) tumors (HR, 1.34; 95% CI, 1.17-1.54 and HR, 1.91; 95% CI, 1.66-2.19, respectively). PFS and OS were significantly decreased for patients with BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT).
Prevalence of dMMR and BRAF(MT) in patients with mCRC is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by the BRAF(MT) status.
Objective To examine changes in representation of women among first authors of original research published in high impact general medical journals from 1994 to 2014 and investigate differences ...between journals.Design Observational study.Study sample All original research articles published in Annals of Internal Medicine, Archives of Internal Medicine, The BMJ, JAMA, The Lancet, and the New England Journal of Medicine (NEJM) for one issue every alternate month from February 1994 to June 2014.Main exposures Time and journal of publication.Main outcome measures Prevalence of female first authorship and its adjusted association with time of publication and journal, assessed using a multivariable logistic regression model that accounted for number of authors, study type and specialty/topic, continent where the study was conducted, and the interactions between journal and time of publication, study type, and continent. Estimates from this model were used to calculate adjusted odds ratios against the mean across the six journals, with 95% confidence intervals and P values to describe the associations of interest.Results The gender of the first author was determined for 3758 of the 3860 articles considered; 1273 (34%) were women. After adjustment, female first authorship increased significantly from 27% in 1994 to 37% in 2014 (P<0.001). The NEJM seemed to follow a different pattern, with female first authorship decreasing; it also seemed to decline in recent years in The BMJ but started substantially higher (approximately 40%), and The BMJ had the highest total proportion of female first authors. Compared with the mean across all six journals, first authors were significantly less likely to be female in the NEJM (adjusted odds ratio 0.68, 95% confidence interval 0.53 to 0.89) and significantly more likely to be female in The BMJ (1.30, 1.01 to 1.66) over the study period.Conclusions The representation of women among first authors of original research in high impact general medical journals was significantly higher in 2014 than 20 years ago, but it has plateaued in recent years and has declined in some journals. These results, along with the significant differences seen between journals, suggest that underrepresentation of research by women in high impact journals is still an important concern. The underlying causes need to be investigated to help to identify practices and strategies to increase women’s influence on and contributions to the evidence that will determine future healthcare policies and standards of clinical practice.
Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product ...users.
To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users.
A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105).
The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655).
Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs).
Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure.
Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.
Abstract
Background
Consumer perceptions of legal cannabis products may drive willingness to purchase from the illegal or legal market; however, little is known on this topic. The current study ...examined perceptions of legal products among Canadian cannabis consumers over a 3-year period following federal legalization of non-medical cannabis in 2018.
Methods
Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted in 2019–2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models examined the association between perceptions of legal cannabis and province of residence, and frequency of cannabis use over time.
Results
In 2021, cannabis consumers perceived legal cannabis to be safer to buy (54.0%), more convenient to buy (47.8%), more expensive (47.2%), safer to use (46.8%) and higher quality (29.3%) than illegal cannabis. Except for safety of purchasing, consumers had more favourable perceptions of legal cannabis in 2021 than 2019 across all outcomes. For example, consumers had higher odds of perceiving legal cannabis as more convenient to buy in 2021 than 2019 (AOR = 3.09, 95%CI: 2.65,3.60). More frequent consumers had less favourable perceptions of legal cannabis than less frequent consumers.
Conclusions
Three years since legalization, Canadian cannabis consumers generally had increasingly favourable perceptions of legal vs. illegal products – except for price – with variation across the provinces and frequency of cannabis use. To achieve public health objectives of legalization, federal and provincial governments must ensure that legal cannabis products are preferred to illegal, without appealing to non-consumers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of ...patients with Hodgkin transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of two therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was one (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95% Confidence Interval: 62-83). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; P=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.
Background
There is increasing recognition of the importance of addressing health literacy in patient decision aid (PtDA) development.
Purpose
An updated review as part of IPDAS 2.0 examined the ...extent to which PtDAs are designed to meet the needs of people with low health literacy/socially-disadvantaged populations.
Data Sources
Reference lists of Cochrane reviews of randomized controlled trials (RCTs) of PtDAs (2014, 2017, and upcoming 2021 versions).
Study Selection
RCTs that assessed the impact of PtDAs on low health literacy or other socially-disadvantaged groups (i.e., ≥50% participants from socially-disadvantaged groups and/or subgroup analysis in socially-disadvantaged group/s).
Data Extraction
Two researchers independently extracted data into a standardized form including PtDA development and evaluation details. We searched online repositories and emailed authors to access PtDAs to verify grade reading level, understandability, and actionability.
Data Synthesis
Twenty-five of 213 RCTs met the inclusion criteria, illustrating that only 12% of studies addressed the needs of low health literacy or other socially-disadvantaged groups. Grade reading level was calculated in 8 of 25 studies (33%), which is recommended in previous IPDAS guidelines. We accessed and independently assessed 11 PtDAs. None were written at sixth-grade level or below. Ten PtDAs met the recommended threshold for understandability, but only 5 met the recommended threshold for actionability. We also conducted a post hoc subgroup meta-analysis and found that knowledge improvements after receiving a PtDA were greater in studies that reported using strategies to reduce cognitive demand in PtDA development compared with studies that did not (χ2 = 14.11, P = 0.0002, I2 = 92.9%).
Limitations
We were unable to access 13 of 24 PtDAs. Conclusions. Greater attention to health literacy and socially-disadvantaged populations is needed in the field of PtDAs to ensure equity in decision support.
Smoking cannabis may potentially increase exposure to numerous toxic chemicals that are commonly associated with tobacco use. There is a paucity of data related to toxicant exposures among concurrent ...users of tobacco and cannabis ("co-users").
Data are from the PATH Study Wave 1 Biomarker Restricted-Use Files. Analyses focused on adults who provided urine samples (n=5,859). Urine samples were analyzed for biomarkers of exposure to nicotine, tobacco specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Using weighted linear regression, we compared adjusted geometric mean concentrations of 15 biomarkers between user groups of various tobacco product types according to their self-reported past 30-day cannabis use.
Past 30-day cannabis use was similar across various types of tobacco product use subgroups (range: 13%-23%) and significantly more common compared to non-tobacco users (1.0%; p<0.001). Across all groups of tobacco users, those who co-used cannabis exhibited significantly higher concentrations of the biomarker of exposure to acrylonitrile (CYMA) compared to non-cannabis users (by 39%-464%). Tobacco-cannabis co-users also showed significantly elevated levels of the biomarker of exposure to acrylamide (AAMA) compared to exclusive tobacco users, and significantly higher exposure to many PAHs (including fluorene and pyrene).
Co-users exhibited higher concentrations for biomarkers of exposure to many combustion byproducts, compared to exclusive tobacco users. More robust measurements of cannabis use can address potential confounding in assessments of exposures to tobacco-related constituents, and potential health effects resulting from co-use.
With disproportionately greater rates of cannabis use occurring among tobacco users, it is critical to consider how concurrent cannabis use may influence health-related outcomes among smokers. Our findings suggest potential additive toxicant exposures among co-users of tobacco and cannabis. Lack of consideration and measurement of cannabis use in assessing tobacco-related exposures may confound estimates thought to be attributable to tobacco, particularly for non-specific biomarkers. Assessing tobacco and cannabis use in tandem will allow for more precise measurement of outcomes related to one or both substances, and can provide additional information on potential health effects related to co-use.
Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against ...certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heated tobacco products (HTPs), such as IQOS, glo, and Ploom TECH, with a variety of flavored tobacco-containing inserts, have reportedly achieved a significant market share in Japan. We analyzed ...data from Wave 1 of the ITC Japan Survey, a nationally representative web survey conducted in February to March 2018 among 4684 adult participants to estimate the prevalence of HTP use, describe characteristics of HTP users, and explore user preferences for HTP device and flavor. The overall prevalence of monthly HTP use was 2.7% (1.7% daily use). Virtually all HTP users were current cigarette smokers (67.8%) or former smokers (25.0%); only 1.0% of HTP users were never smokers. Among HTP users, IQOS was the most frequently reported brand used (64.5%), and menthol was the most common flavor reported (41.5%). IQOS was used more by younger respondents and those who reported daily use, while Ploom TECH was more popular among older respondents and non-daily HTP users. This is one of the first non-industry funded studies to explore the use of HTPs in Japan.
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