51628 research outputs found
Sort by
Measuring quality of life using patient-reported outcomes in real-world metastatic breast cancer patients
No full textMetastatic breast cancer (MBC) patients are almost always treated to minimize the symptom burden, and to prolong life without a curative intent. Although the prognosis of MBC patients has improved in recent years, the median survival after diagnosis is still only 3 years. Therefore, the health-related quality of life (HRQoL) should play a leading role in making treatment decisions. Heterogeneity in questionnaires used to evaluate the HRQoL in MBC patients complicates the interpretability and comparability of patient-reported outcomes (PROs) globally. In this review, we aimed to provide an overview of PRO instruments used in real-world MBC patients and to discuss important issues in measuring HRQoL. Routinely collecting symptom information using PROs could enhance treatment evaluation and shared decision-making. Standardizing these measures might help to improve the implementation of PROs, and facilitates collecting and sharing data to establish valid comparisons in research. This is a prerequisite to learn about how they could impact the clinical care pathway. In addition, the prognostic value of intensified PRO collection throughout therapy on survival and disease progression is promising. Future perspectives in the field of PROs and MBC are described.</p
Global burden of cancer in 2020 attributable to alcohol consumption
No full textBackground: Alcohol use is causally linked to multiple cancers. We present global, regional, and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally. Methods: In this population-based study, population attributable fractions (PAFs) calculated using a theoretical minimum-risk exposure of lifetime abstention and 2010 alcohol consumption estimates from the Global Information System on Alcohol and Health (assuming a 10-year latency period between alcohol consumption and cancer diagnosis), combined with corresponding relative risk estimates from systematic literature reviews as part of the WCRF Continuous Update Project, were applied to cancer incidence data from GLOBOCAN 2020 to estimate new cancer cases attributable to alcohol. We also calculated the contribution of moderate (<20 g per day), risky (20–60 g per day), and heavy (>60 g per day) drinking to the total alcohol-attributable cancer burden, as well as the contribution by 10 g per day increment (up to a maximum of 150 g). 95% uncertainty intervals (UIs) were estimated using a Monte Carlo-like approach. Findings: Globally, an estimated 741 300 (95% UI 558 500–951 200), or 4·1% (3·1–5·3), of all new cases of cancer in 2020 were attributable to alcohol consumption. Males accounted for 568 700 (76·7%; 95% UI 422 500–731 100) of total alcohol-attributable cancer cases, and cancers of the oesophagus (189 700 cases [110 900–274 600]), liver (154 700 cases [43 700–281 500]), and breast (98 300 cases [68 200–130 500]) contributed the most cases. PAFs were lowest in northern Africa (0·3% [95% UI 0·1–3·3]) and western Asia (0·7% [0·5–1·2]), and highest in eastern Asia (5·7% [3·6–7·9]) and central and eastern Europe (5·6% [4·6–6·6]). The largest burden of alcohol-attributable cancers was represented by heavy drinking (346 400 [46·7%; 95% UI 227 900–489 400] cases) and risky drinking (291 800 [39·4%; 227 700–333 100] cases), whereas moderate drinking contributed 103 100 (13·9%; 82 600–207 200) cases, and drinking up to 10 g per day contributed 41 300 (35 400–145 800) cases. Interpretation: Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers. Funding: None.</p
EQ-5D-5L Population Norms and Health Inequality in Colombia
No full textObjectives: The EQ-5D-3L and EQ-5D-5L instruments have been used in studies of patient and demographic groups in Colombia, but to date there are no 5L population norms. This study aimed to produce a set of EQ-5D-5L population norms for Colombia and to see what insights into health inequality in Colombia can be discerned from these norms. Methods: The EQ-5D-5L self-reported health questionnaire was included in a survey of a representative sample of 3400 adults aged 18 to 64 in Colombia. EQ-5D-5L states, mean EQ VAS, and index values were obtained by sex, age, education, income group, ethnicity, residence, employment status, health insurance status, and household size. EQ-5D-5L index values from Uruguay were used. Regression models were used to investigate inequality. Results: The mean EQ VAS value was 85.3, the mean index value was 0.953, and 52.2% of the sample reported being in state 11111. Self-reported health was higher for men, declined in higher age groups, and was lower for lower-income and education groups. The EQ-5D-5L instrument was observed to be more sensitive than the EQ-5D-3L instrument in Colombia. The dimensions with the highest prevalence of reported problems were anxiety/depression and pain/discomfort. The main drivers of inequality were age, sex, income, and education. Conclusions: The population norms developed in this study can be used as baseline values for future studies of patient or treatment groups, and for investigations into the health of specific demographic groups.</p
Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus
No full textBACKGROUND: Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF). METHODS: Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN). RESULTS: In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + ≤7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as 'non-responders' due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA+ patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19+ B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20+ B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier. CONCLUSIONS: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM.</p
Autoimmune encephalitis
No full textThe objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.</p
Why did informal sector workers stop paying for health insurance in Indonesia?
No full textIndonesia faces a growing informal sector in the wake of implementing a national social health insurance system—Jaminan Kesehatan Nasional (JKN)—that supersedes the vertical programmes historically tied to informal employment. Sustainably financing coverage for informal workers requires incentivising enrolment for those never insured and recovering enrolment among those who once paid but no longer do so. This study aims to assess the ability- and willingness-to-pay of informal sector workers who have stopped paying the JKN premium for at least six months, across districts of different fiscal capacity, and explore which factors shaped their willingness and ability to pay using qualitative interviews. Surveys were conducted for 1,709 respondents in 2016, and found that informal workers’ average ability and willingness to pay fell below the national health insurance scheme’s premium amount, even as many currently spend more than this on healthcare costs. There were large groups for whom the costs of the premium were prohibitive (38%) or, alternatively, they were both technically willing and able to pay (25%). As all individuals in the sample had once paid for insurance, their main reasons for lapsing were based on the uncertain income of informal workers and their changing needs. The study recommends a combination of strategies of targeting of subsidies, progressive premium setting, facilitating payment collection, incentivising insurance package upgrades and socialising the benefits of health insurance in informal worker communities.</p
Intestinal multicellular organoids to study colorectal cancer
No full textModeling colorectal cancer (CRC) using organoids has burgeoned in the last decade, providing enhanced in vitro models to study the development and possible treatment options for this type of cancer. In this review, we describe both normal and CRC intestinal organoid models and their utility in the cancer research field. Besides highlighting studies that develop epithelial CRC organoid models, i.e. organoids without tumor microenvironment (TME) cellular components, we emphasize on the need for TME in CRC modeling, to help reduce translational disparities in this area. Also, we discuss the utilization of CRC organoids derived from pluripotent stem cells, as well as their potential to be used in cancer research. Finally, limitations and challenges in the current CRC organoids field, are discussed.</p
Low Microcirculatory Perfused Vessel Density and High Heterogeneity are Associated With Increased Intensity and Duration of Lactic Acidosis After Cardiac Surgery with Cardiopulmonary Bypass
No full textINTRODUCTION: Lactic acidosis after cardiac surgery with cardiopulmonary bypass is common and associated with an increase in postoperative morbidity and mortality. A number of potential causes for an elevated lactate after cardiopulmonary bypass include cellular hypoxia, impaired tissue perfusion, ischemic-reperfusion injury, aerobic glycolysis, catecholamine infusions, and systemic inflammatory response after exposure to the artificial cardiopulmonary bypass circuit. Our goal was to examine the relationship between early abnormalities in microcirculatory convective blood flow and diffusive capacity and lactate kinetics during early resuscitation in the intensive care unit. We hypothesized that patients with impaired microcirculation after cardiac surgery would have a more severe postoperative hyperlactatemia, represented by the lactate time-integral of an arterial blood lactate concentration greater than 2.0 mmol/L. METHODS: We measured sublingual microcirculation using incident darkfield video microscopy in 50 subjects on intensive care unit admission after cardiac surgery. Serial measurements of systemic hemodynamics, blood gas, lactate, and catecholamine infusions were recorded each hour for the first 6 h after surgery. Lactate area under the curve (AUC) was calculated over the first 6 h. The lactate AUC was compared between subjects with normal and low perfused vessel density (PVD < 18 mm/mm2), high microcirculatory heterogeneity index (MHI > 0.4), and low vessel-by-vessel microvascular flow index (MFIv < 2.6). RESULTS: Thirteen (26%) patients had a low postoperative PVD, 20 patients (40%) had a high MHI, and 26 (52%) patients had a low MFIv. Patients with low perfused vessel density had higher lactate AUC compared with subjects with a normal PVD (22.3 [9.4-31.0] vs. 2.6 [0-8.8]; P < 0.0001). Patients with high microcirculatory heterogeneity had a higher lactate AUC compared with those with a normal MHI (2.5 [0.1-8.2] vs. 13.1 [3.7-31.1]; P < 0.001). We did not find a difference in lactate AUC when comparing high and low MFIv. CONCLUSION: Low perfused vessel density and high microcirculatory heterogeneity are associated with an increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass.</p
Direct detection of SARS-CoV-2 antisense and sense genomic RNA in human saliva by semiautonomous fluorescence in situ hybridization
No full textSaliva is a matrix which may act as a vector for pathogen transmission and may serve as a possible proxy for SARS-CoV-2 contagiousness. Therefore, the possibility of detection of intracellular SARS-CoV-2 in saliva by means of fluorescence in situ hybridization is tested, utilizing probes targeting the antisense or sense genomic RNA of SARS-CoV-2. This method was applied in a pilot study with saliva samples collected from healthy persons and those presenting with mild or moderate COVID-19 symptoms. In all participants, saliva appeared a suitable matrix for the detection of SARS-CoV-2. Among the healthy, mild COVID-19-symptomatic and moderate COVID-19-symptomatic persons, 0%, 90% and 100% tested positive for SARS-CoV-2, respectively. Moreover, the procedure allows for simultaneous measurement of viral load ('presence', sense genomic SARS-CoV-2 RNA) and viral replication ('activity', antisense genomic SARS-CoV-2 RNA) and may yield qualitative results. In addition, the visualization of DNA in the cells in saliva provides an additional cytological context to the validity and interpretability of the test results. The method described in this pilot study may be a valuable diagnostic tool for detection of SARS-CoV-2, distinguishing between 'presence' (viral load) and 'activity' (viral replication) of the virus. Moreover, the method potentially gives more information about possible contagiousness. </p
Sex workers’ everyday security in the Netherlands and the impact of COVID-19
Get PDFThe COVID-19 pandemic has laid bare and exacerbates the existing
insecurities of sex workers, a highly stigmatised, often criminalised and
economically precarious group of workers. In the Netherlands, sex workers
continue to experience different forms of violence despite the occupation’s
legalisation, making it a ‘profession in limbo’. This paper therefore seeks to
formulate answers to the questions: What are sex workers’ everyday
experiences of (in)security? And: How has the COVID-19 pandemic
influenced these? Given sex workers’ historical exclusion from policy
formulation, we engage with these questions through collaborative research
based on semi-structured interviews with sex workers in The Hague.
Our analysis reveals a stark mismatch between the insecurities that sex
workers’ experience and the concerns enshrined in the regulatory environment.
While the municipality’s regulation of the sex industry focuses on sexually
transmitted infections (STIs), occupational safety and health issues that sex
workers experience also include psychological problems, insufficient hygiene in
the workplace and the risk of violent clients. Besides, income insecurity is a key
concern for sex workers. The decline in legal workspaces during the past two
decades has not translated into higher service rates. Net earnings are further
reduced when window operators pass on the risks of illness or damage to sex
workers. Furthermore, operators act as powerful gatekeepers of access to
remunerative employment. Here, sex workers identify gender-based
discrimination with resulting more severe employment and income insecurities
for transwomen and male sex workers.
This legal liminality is enabled not only by the opaque legal status of sex
work in the Netherlands, but also by the gendering of official regulation. Our
study mirrors research from the Netherlands and beyond that documents sex
workers’ widespread exclusion from COVID-19 support packages. Over and
beyond this, we find that immigration status intersects with and mediates these
exclusionary processes.
We conclude that, firstly, to effectively address the insecurities that sex
workers experience and fear, regulation needs to shift from its current criminal
law and public health focus to a labour approach. Secondly, over and above
such decriminalization, policies and civil society actors alike need to address
the gender and sexual hierarchies that underpin sex worker stigma as well as
migrants’ discrimination which have come out as powerful mediators of sex
workers’ insecurities